# projects

application_id: 7382119
project_number: 5P20RR020145-03
project_title: UKY DENTAL COBRE: ORAL INFECTIONS: VIRAL INFECTIONS IN CHRONIC ORAL DISEASES
administering_ic: NCRR
award_notice_date: 2006-07-31
opportunity_number: RFA-RR-03-014
application_type: 5
activity_code: P20
ic: RR
serial_number: 020145
project_start_date: 2006-08-01
project_end_date: 2007-07-31
study_section: ZRR1-RI-5(02)
subproject_number: 7510
contact_pi_person_id: 9185054
contact_pi: LI, MENGTAO
other_pis: Not Applicable
congressional_district: 06
department: DENTISTRY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF DENTISTRY/ORAL HYGN
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. Although bacteria are the primary pathogens in periodontitis human herpesviruses have a purported relationship with inflamed periodontal tissues. This could be important because herpesviruses modulate host immune responses through a variety of mechanisms. The goal of this research was to test the hypothesis that herpesviruses enhance the pathogenesis of periodontal diseases. Our hypothesis is being examined using three approaches: 1) determine the role of herpesviruses in periodontitis by analyzing clinical samples from patients with and without periodontal disease 2) investigating the ability of herpesvirus to enhance the progression of periodontitis in the rat model; and 3) define mechanisms of immunomodulation by cytomegalovirus (CMV). We have initiated a plan to recruit 100 patients with periodontal disease and collect dental plaques and saliva samples. Real-time PCR will be used to detect DNA of human herpesvirus in plaque from healthy and diseased sites and parallel saliva samples. This method that has been successfully used to identify all 8 HHVs in saliva is being optimized to detect viral DNA in plaque. In the second project we have obtained rat CMV (RCMV) Maastricht strain propagated lab stocks and obtained titers on the virus. Animal inoculation(s) with P. gingivalis and/or RCMV will be initiated in early summer 2005. In the study of molecular mechanisms of immunomodulation by CMV we have successfully constructed and purified a recombinant CMV that expresses GFP (green fluorescence protein). In addition we cloned CMV vIL-10 gene. We discovered 5 previously unidentified vIL-10 isoforms. We are in the process of characterizing 8 different vIL-10 isoforms in vitro and analyzing their amino acid sequences using bioinformatics methods. Because CMV vIL-10 is a potent immune suppressor we are initiating study to determine its roles in modulating the host response of oral epithelia and gingival fibroblasts against bacterial invasion.


application_id: 7382118
project_number: 5P20RR020145-03
project_title: UKY DENTAL COBRE: ORAL INFECTIONS: DIETARY REGULATION OF INFLAMMATORY RESPONSES
administering_ic: NCRR
award_notice_date: 2006-07-31
opportunity_number: RFA-RR-03-014
application_type: 5
activity_code: P20
ic: RR
serial_number: 020145
project_start_date: 2006-08-01
project_end_date: 2007-07-31
study_section: ZRR1-RI-5(02)
subproject_number: 7509
contact_pi_person_id: 8263389
contact_pi: DAWSON, DOLPH R.
other_pis: Not Applicable
congressional_district: 06
department: DENTISTRY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF DENTISTRY/ORAL HYGN
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. Periodontal disease is a chronic inflammatory condition that may have a significant negative impact on systemic conditions such as diabetes and cardiovascular disease. Previous studies have suggested that controlling oral infection and inflammation may have beneficial systemic effects. Studies have also shown that many well-recognized disorders are associated with excessive intake of dietary fat including obesity insulin resistance coronary heart disease and some forms of cancer. While intake of saturated trans and arachidonic fatty acids has been linked to the development of chronic disease research shows n-3 polyunsaturated fatty acids (n-3 PUFA) specifically fish oils (e.g. Cold-water fish such as mackerel) can contribute to the prevention and treatment of disease. Dietary n-3 PUFA provides a benefit by reducing inflammation and improving antibacterial and autoimmune responses in many chronic inflammatory medical conditions. It is hypothesized that the use of n-3 PUFA as a dietary supplement could have an important impact on systemic health by reducing chronic periodontal disease and systemic inflammation either alone or when combined with periodontal therapy. This project will study the effects of dietary n-3 PUFA capsules (1000 mg t.i.d.) compared to placebo (corn/soybean oil) capsules in 200 subjects with generalized periodontitis a condition known to have negative systemic outcomes and be associated with a hyper-inflammatory phenotype as demonstrated by elevated inflammatory cell function and elevated systemic levels of C-reactive protein (CRP). Using a randomized double-blind placebo controlled intervention study of 4 groups (50 subjects per group) we will study the effects of combining n-3 PUFA or placebo with oral hygiene or scaling and root planing on systemic inflammation (measured by CRP); periodontal inflammation and clinical outcomes (clinical measures and inflammatory mediators in gingival crevicular fluid); and bacterial colonization of plaque (changes in levels of P. gingivalis T. denticola and T. forsythensis). A three month period of study organization followed the notification of funding in September 2004. Therefore initial study recruitment did not begin until early 2005. Currently there have been four subjects enrolled into the study; 104 subjects pre-screened and 30 qualified and ready for enrollment. No data analysis has been done.


application_id: 7382117
project_number: 5P20RR020145-03
project_title: UKY DENTAL COBRE: ORAL INFECTIONS: IMPACT ON GESTATIONAL DIABETES
administering_ic: NCRR
award_notice_date: 2006-07-31
opportunity_number: RFA-RR-03-014
application_type: 5
activity_code: P20
ic: RR
serial_number: 020145
project_start_date: 2006-08-01
project_end_date: 2007-07-31
study_section: ZRR1-RI-5(02)
subproject_number: 7508
contact_pi_person_id: 1880406
contact_pi: NOVAK, KAREN F.
other_pis: Not Applicable
congressional_district: 06
department: DENTISTRY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF DENTISTRY/ORAL HYGN
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. Gestational Diabetes Mellitus (GDM) occurs in approximately 5% of pregnant women with onset during pregnancy and subsiding after parturition. Importantly nearly 50% of women with GDM will eventually develop type 2 diabetes mellitus within 3-5 years post-partum. Moreover acute and chronic neonatal morbidity and mortality have been described in neonates delivered by women with GDM. Substantial evidence is available documenting that the severity of periodontal disease is increased in patients with type 2 diabetes but no data are available on the effects of GDM on periodontal health. In addition substantial data is accruing to support earlier observations that the infection and inflammation associated with periodontal disease may have a negative impact on the period of gestation and on fetal growth leading to the birth of preterm low birth weight infants. Our GENERAL HYPOTHESIS is that women with GDM are at higher risk for developing more severe periodontal disease than women without GDM and that the combination of GDM and periodontal disease will be associated with an increased negative impact on maternal and fetal health. This hypothesis will be tested by collecting (a) clinical oral health data on periodontal status as well as maternal and fetal outcomes data (Specific Aim 1) (b) microbial dental plaque samples (Specific Aim 2) and (c) serum samples in women with GDM and in non-GDM controls (Specific Aim 3). These prospective clinical data will be correlated with basic science laboratory evaluations of the microflora and host response to provide insight into the pathogenic mechanisms contributing to negative maternal and fetal outcomes associated with inflammatory periodontal disease and GDM. To date 25 subjects have enrolled in the study. The appropriate data have been collected on all subjects. Enrollment will continue in the coming year. Collected data will be subjected to statistical analyses at the mid-point and at the end of the study.


application_id: 7382116
project_number: 5P20RR020145-03
project_title: UKY DENTAL COBRE: POLYBACTERIAL PERIODONTITIS: N-3 PUFA AND ANTIOXIDANTS
administering_ic: NCRR
award_notice_date: 2006-07-31
opportunity_number: RFA-RR-03-014
application_type: 5
activity_code: P20
ic: RR
serial_number: 020145
project_start_date: 2006-08-01
project_end_date: 2007-07-31
study_section: ZRR1-RI-5(02)
subproject_number: 7507
contact_pi_person_id: 7875070
contact_pi: LAKSHMYYA, KESAVALU NAIDU
other_pis: Not Applicable
congressional_district: 06
department: DENTISTRY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF DENTISTRY/ORAL HYGN
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The original Project 3 focused on polymicrobial infections inducing inflammation and bone loss using a murine calvarial model. It was designed to examine synergistic virulence effects of P. gingivalis T. forsythensis and T. denticola. Additionally the aims were developed to determine the impact of acquired immune responses to infection and active immunity following immunization of the inflammation and tissue destruction. Following submission of the COBRE and prior to its funding in Sept. 2004 this research was funded as an R01 from the NIDCR. Thus the COBRE grant provided the PI Dr. Kesavalu a ?Transition Award? to extend his research and contribute to submission of a 2nd R01 application. The funding provided support for a pilot study initiated to document the ability to infect the oral cavity of rats with the polymicrobial consortium of P. gingivalis (Pg) T. denticola (Td) and T. forsythia (Tf) (Pg/Td/Tf). This was compared to the potential that incorporation of F. nucleatum (bridging and coaggregating pathogen) into this mixture (Pg/Td/Tf/Fn) would enhance the effectiveness of the infection regimen. Using an modified infection procedure rats were challenged orally on 5 consecutive days with a 2% CMC solution containing a mixture of the microorganisms. The molar teeth were swabbed DNA isolated from oral samples and assessed using PCR for the presence of the bacteria. The results demonstrated seminal data that the rats were infected with the polymicrobial pathogenic consortia. Rats were euthanized the gingival tissues collected and snap frozen in liquid nitrogen. Blood and rat jaws also were collected for serum IgG antibody and assessment of alveolar bone resorption. A significant serum antibody response to members of the polymicrobial infection was noted supporting oral tissue infection and systemic challenge by the oral infection. Interestingly the polymicrobial challenge with the Pg/Td/Tf/Fn consortium (5 days 1 time during the 12 weeks) appeared to elicited substantially greater antibody. Alveolar bone loss in rats infected with these consortia demonstrated 2 primary findings. The single infection regimen with the Pg/Td/Tf challenged elicited minimal bone loss supporting that a single challenge regimen is not sufficient to establish and maintain a disease process. However the Pg/Td/Tf/Fn consortium with a minimal infection challenge induced significant bone loss that was significantly greater than noted with any of the monoinfections which had received the challenge multiple times during the 12 weeks. These findings provided additional preliminary data in support of an R01 application that is currently under review at the NIH. The aims of this proposal include: SPECIFIC AIM 1: To determine the effect of n-3 PUFA to modulate periodontal inflammation and alveolar bone loss induced by the pathogenic consortium P. gingivalis-T. forsythia-T. denticola in rats. SPECIFIC AIM 2. To determine the effect of a dietary antioxidant supplement ?-lipoic acid and vitamin E (?-LA/VE) to modulate periodontal inflammation and alveolar bone loss induced by the pathogenic consortium P. gingivalis T. forsythia and T. denticola in rats. SPECIFIC AIM 3. To determine the effect of a potent anti-inflammatory/antioxidant natural dietary substance curcumin to modulate periodontal inflammation and alveolar bone loss induced by the pathogenic consortium P. gingivalis T. forsythia and T. denticola in rats. SPECIFIC AIM 4. To determine the effect of combinations of dietary anti-inflammatories/antioxidants as co-supplements to modulate or decrease periodontal inflammation and alveolar bone loss induced by the pathogenic consortium P. gingivalis T. forsythia and T. denticola in rats.


application_id: 7382115
project_number: 5P20RR020145-03
project_title: UKY DENTAL COBRE: ORAL INFECTIONS: COX-2
administering_ic: NCRR
award_notice_date: 2006-07-31
opportunity_number: RFA-RR-03-014
application_type: 5
activity_code: P20
ic: RR
serial_number: 020145
project_start_date: 2006-08-01
project_end_date: 2007-07-31
study_section: ZRR1-RI-5(02)
subproject_number: 7506
contact_pi_person_id: 8351945
contact_pi: LOFTIN, CHARLES DAVID
other_pis: Not Applicable
congressional_district: 06
department: DENTISTRY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF DENTISTRY/ORAL HYGN
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. Specific Aim 1. Determine the role of COX-2 in P. gingivalis-induced periodontal disease and atherosclerosis. Periodontitis is a chronic inflammatory disease resulting from microbial infection of the oral cavity. The disease is initiated by gram-negative anaerobic species including Porphyromonas gingivalis. P. gingivalis infection may produce inflammation localized within the oral cavity which results in alveolar bone resorption and may produce a systemic inflammatory response resulting from bacteremia. The systemic inflammatory response is thought to account for the increased risk of developing complications of cardiovascular disease in patients with periodontitis. Prostaglandins are a class of inflammatory mediators that are significantly increased in diseased periodontal tissues. The synthesis of prostaglandins requires the activity of a cyclooxygenase and cyclooxygenase-2 (COX-2) is the isoform that is highly induced by gram-negative bacterial products and is increased in atherosclerotic lesions. The current studies utilized an established mouse model of P. gingivalis-induced periodontitis to examine the role of COX-2-derived prostaglandins in alveolar bone resorption and atherosclerosis. Alveolar bone resorption and cardiovascular disease resulting from P. gingivalis requires chronic infection to be established in the oral cavity of the mice. Therefore the mice are inoculated with P. gingivalis 4 days a week every 3rd week over a 12 week course. We have optimized the PCR technique to confirm that chronic infection with P. gingivalis is established in the mice. We have also utilized the highly sensitive technique real-time PCR to examine the expression of COX-2 as well as downstream prostaglandin synthases in aortic tissue. Furthermore we have optimized immunohistochemical analysis for detection of COX-2 protein expression in the aortas of mice. These procedures will allow us to examine the effects of P. gingivalis infection on the expression of COX-2 and downstream prostaglandin synthases. Studies are in progress to examine the effectiveness of genetic or pharmacological inactivation of COX-2 in reducing P. gingivalis-induced alveolar bone resorption and atherosclerosis in mice.  Specific Aim 2. Define the role of 12/15-lipoxygenase in P. gingivalis-induced periodontal disease and atherosclerosis. Angiotensin II (AngII) markedly accelerates atherogenesis in hyperlipidemic mice. Moreover AngII increases the expression of 12/15-lipoxygenase (12/15-LO). Deficiency of 12/15-LO markedly attenuates atherosclerosis in hyperlipidemic mice.  Therefore we sought to determine if 12/15-LO plays a role in AngII-induced vascular disease. Age matched male apolipoproteinE deficient (apoE-/-) mice or 12/15-LO deficient apoE-/- mice were infused with AngII (1000 ng/kg/min) for 28 days. Total serum cholesterol or lipoprotein profile was not altered in 12/15-LO deficient mice following AngII infusion compared to control. 12/15-LO modestly decreased AngII-induced atherosclerotic lesion formation (12/15-LO+/+: 1.26% vs 12/15-LO-/-: 1.99%; P = 0.12) on the intimal surface of the aortic arch however this decrease did not reach statistical significance. Additionally 12/15-LO deficiency decreased the incidence of AngII-induced abdominal aortic aneurysm formation (12/15-LO+/+: 42% vs 12/15-LO-/-: 17%; P = 0.12) and the abdominal aortic diameter (12/15-LO+/+: 1.6 mm vs 12/15-LO-/-: 1.1 mm; P = 0.11) however the reduction in both of these parameters did not reach statistical significance. While these results suggest 12/15-LO does not significantly alter AngII-induced atherosclerosis and AAA formation the number of mice utilized in these studies did not result in a power of 0.08. This coupled with the trend toward a decrease in both atherosclerosis and AAA formation suggest that additional studies are required to define the effect of 12/15-LO on AngII-induced vascular disease.


application_id: 7382114
project_number: 5P20RR020145-03
project_title: UKY DENTAL COBRE: DENTAL CLINICAL RESEARCH CENTER
administering_ic: NCRR
award_notice_date: 2006-07-31
opportunity_number: RFA-RR-03-014
application_type: 5
activity_code: P20
ic: RR
serial_number: 020145
project_start_date: 2006-08-01
project_end_date: 2007-07-31
study_section: ZRR1-RI-5(02)
subproject_number: 7505
contact_pi_person_id: 7875071
contact_pi: NOVAK, MICHAEL JOHN
other_pis: Not Applicable
congressional_district: 06
department: DENTISTRY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF DENTISTRY/ORAL HYGN
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. A primary focus of the DDKCRC is to create a research infrastructure to: 1) develop and train clinical research professionals research coordinators and research staff and 2) define and impact oral health disparities in rural communities of Kentucky. An initial emphasis will be on investigations to determine oral-systemic disease linkages in these rural populations and to define biological genetic and socio-behavioral factors contributing to these disparities. The DDKCRC personnel have focused on the preparation and submission of forms for IRB approval for Projects 4 5 and 6 for the center. These have all been obtained and the projects initiated. The personnel have contributed to the recruitment of patients for these same projects as well as collecting biological specimens for the projects. In addition the DDKCRC will be supporting the clinical research needs of the Pilot Project on Alzheimer?s Disease (Dr. Stein) and the new full project on Smoking Genotypes (Dr. Al-Sabbagh). Finally the laboratory personnel in the DDKCRC have provided support for evaluation of host analytes for Projects 2 4 5 and 6. In addition the laboratory has developed a real-time quantitative PCR methodology for assessment of target microorganisms in the subgingival plaque allowing improved evaluation of microbial changes in Projects 4 5 and 6.


application_id: 7382113
project_number: 5P20RR020145-03
project_title: UKY DENTAL COBRE: BIOINFORMATICS & BIOSTATISTICS CORE
administering_ic: NCRR
award_notice_date: 2006-07-31
opportunity_number: RFA-RR-03-014
application_type: 5
activity_code: P20
ic: RR
serial_number: 020145
project_start_date: 2006-08-01
project_end_date: 2007-07-31
study_section: ZRR1-RI-5(02)
subproject_number: 7504
contact_pi_person_id: 1874302
contact_pi: KRYSCIO, RICHARD J
other_pis: Not Applicable
congressional_district: 06
department: DENTISTRY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF DENTISTRY/ORAL HYGN
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. This core provides expert advice on experimental design data management subject recruitment and data analysis to the clinical projects in this COBRE and it provides expertise on the analysis of the bioinformatics data generated in the basic science projects. This advice promotes efficiency in terms of the minimal number of patients to be recruited to a clinical study or the minimum number of chips to be processed in a microarray experiment so that information is maximized. Advice rendered at an early stage in the design of the project makes a difference. It also significantly improves the chances that the project will be successful as evidenced by the role this core played in one success in each area. Inherent in this core is a training component since its personnel supervise graduate students trainees in their own discipline and work on a one to one basis with young investigators in the dental sciences. The younger faculty in this core are also mentored by the senior faculty. A journal paper summarizing a pilot project supporting a current clinical project and several abstracts based on related dental graduate student research have been submitted. An R01 application in the basic science area in which this core provided key technical support has been awarded and another application is in progress. As the projects in this COBRE mature personnel in this core will analyze the data generated and when needed will create new methodology to help interpret the results.


application_id: 7382112
project_number: 5P20RR020145-03
project_title: UKY DENTAL COBRE: ADMINISTRATIVE AND EDUCATIONAL CORE
administering_ic: NCRR
award_notice_date: 2006-07-31
opportunity_number: RFA-RR-03-014
application_type: 5
activity_code: P20
ic: RR
serial_number: 020145
project_start_date: 2006-08-01
project_end_date: 2007-07-31
study_section: ZRR1-RI-5(02)
subproject_number: 7503
contact_pi_person_id: 1897360
contact_pi: EBERSOLE, JEFFREY L
other_pis: Not Applicable
congressional_district: 06
department: DENTISTRY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF DENTISTRY/ORAL HYGN
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The Administrative/Educational Core of the CBBO/SD has facilitated the research and training goals of the COBRE during this initial funding period by: (1) To schedule and organize meetings for the CBBO/SD participants; (2) To organize meetings of the Scientific Advisory Committee (SAC); (3) To provide fiscal administration and accounting; (4) To interface with institutional administration in new faculty recruitment; (5) To oversee the funding of new pilot projects; (6) To interface and provide appropriate reporting to the NIH and other regulatory agencies; (7) To sponsor and organize research career development and training opportunities; and (8) To provide outcomes assessment of the CBBO/SD. During this year the A/E Core has initiated a monthly seminar series in collaboration with the College of Dentistry and the regional chapter of the American Association for Dental Research. This has enabled invited speakers monthly beginning Nov. 2004. We have hired a full-time Administrative Officer to manage the COBRE grant as well as working with investigators across the College of Dentistry to enhance grant submission and the quality of grants management. We have organized a review of both the YIP/OHP (pilot) Grants by the SAC as well as a replacement project for Project #3 that was funded via an R01. The A/E Core is also developing a solicitation for a second round of YIP/OHP and currently hast 3 new junior faculty preparing applications for these pilot grants. The A/E Core has also developed with the junior investigators and mentors tools for assessment of needs and expectations relative to the maturation of the investigators as academic faculty. These tools have been administered to obtain initial information from the group so as to provide yearly monitoring of changing needs. The A/E Core has also begun work with the UK K30 award group to develop training and career development opportunities with shared resources and interacting groups of faculty and fellows particularly as related to clinical research and faculty development.


application_id: 7382111
project_number: 5P20RR020145-03
project_title: UKY DENTAL COBRE: ORAL INFECTIONS AND HIV RECRUDESCENCE
administering_ic: NCRR
award_notice_date: 2006-07-31
opportunity_number: RFA-RR-03-014
application_type: 5
activity_code: P20
ic: RR
serial_number: 020145
project_start_date: 2006-08-01
project_end_date: 2007-07-31
study_section: ZRR1-RI-5(02)
subproject_number: 7502
contact_pi_person_id: 8367053
contact_pi: HUANG, CHIFU BRAD
other_pis: Not Applicable
congressional_district: 06
department: DENTISTRY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF DENTISTRY/ORAL HYGN
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The introduction of HAART regimens (Highly Active Antiretroviral Therapy) has significantly modified the course of HIV disease with longer survival rates and improvement of life quality in HIV-infected individuals. However complete eradication of HIV infection cannot be achieved with currently available antiretroviral regimens. This primarily results from the establishment of a pool of latently infected CD4+ T cells macrophages and other host cells (eg. dendritic cells mast cells) during the very earliest stages of acute HIV infection that persists with an extremely long half-life. This persistence of HIV-1 within various host immune cells including macrophages constitutes a major obstacle in the control of HIV-1 infection. We are using model T cell and macrophage systems to evaluate the capacity of the oral microbial challenges to reactivate HIV. Our initial studies have used the BF24 cell line a human macrophage transfected with the HIV LTR promoter driving a chloramphenicol acetyltransferase (CAT) gene. Specific Aim 1 was to examine the alteration of these cells were challenged with oral bacteria (Pg Sm Cr Fn) or sonicates to assess variations in HIV promoter activation related to species dose and time. We also evaluated the ability of a polymicrobial challenge to synergize in this activation. The outcome was measured using a CAT ELISA. Differences were noted in the ability of the various oral bacteria and bacterial sonicates to activate HIV supporting that the characteristics of oral infection in periodontitis patients could variably impact reactivation of HIV. We also noted that a polybacterial challenge of the BF24 cells demonstrated an additive reactivation when compared to either bacterium alone. Specific Aim 2 focuses on the ability of host induced molecules to reactivate HIV. In these studies we have challenged human gingival fibroblast (HGF) cultures with various bacterial sonicates. The resulting supernatants were then used to stimulate HIV reactivation in the BF24 cells. The findings indicated a dose and time responsiveness for the HGF supernatants to stimulate the BF24 cells. However these reactions appeared substantially less that direct bacterial stimulation of the macrophages. Finally we have initiated some co-culture experiments in which the HGF macrophages and bacterial challenge take place in the same milieu. Initial results suggest that factors in these cultures may actually modulate the ability to activate the HIV promoter. Thus the data demonstrate that oral bacteria have the capacity to activate HIV in latently infected macrophages. There appeared some specificity to the magnitude of this activation and a polybacterial challenge of these infected cells can enhance HIV reactivation. The results suggest chronic oral infections provide a risk to treatment success in HIV infected patients.


application_id: 7382010
project_number: 5P20RR018733-04
project_title: COBRE: LOUISVILLE RES FOUND INC: CORE E: PROTEOMICS FACILITY
administering_ic: NCRR
award_notice_date: 2006-07-27
opportunity_number: RFA-RR-02-007
application_type: 5
activity_code: P20
ic: RR
serial_number: 018733
project_start_date: 2006-07-01
project_end_date: 2007-06-30
study_section: ZRR1-RI-8(01)
subproject_number: 7401
contact_pi_person_id: 2105319
contact_pi: KLEIN, JON
other_pis: Not Applicable
congressional_district: 03
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The Core Proteomics Laboratory is uniquely equipped with robotic workstations that increase gel throughput image analysis spot excision in-gel peptide digestion and MALDI-MS sample preparation. The automated workstations include f Propic gel spot picker that visualizes and excises spots from fluorescence stained gels and a ProGest station that automates in-gel trypsin digestion in a 96- or 384-well format. The laboratory also contains a ProMS robot that automates desalting concentrating and spotting of peptide samples onto MALDI targets allowing fully integrated high-throughput analysis of protein samples. MALDI-MS analysis is performed using a Micromass Inc. TOF-Spec 2E. The lab recently instituted automated analysis of high-resolution 2D gels using Progenesis software significantly decreasing analysis time of 2D gels accelerating throughput.  The CPL maintains active collaborations and provides instruction to COBRE-affiliated faculty and graduate students. In the past year the CPL collaborated with three COBRE-affiliated faculty members and provided instruction in proteomic techniques to two graduate students.


application_id: 7382009
project_number: 5P20RR018733-04
project_title: COBRE: LOUISVILLE RES FOUND INC: CORE D: NMR & PROTEIN PURIFICATION FACILITIES
administering_ic: NCRR
award_notice_date: 2006-07-27
opportunity_number: RFA-RR-02-007
application_type: 5
activity_code: P20
ic: RR
serial_number: 018733
project_start_date: 2006-07-01
project_end_date: 2007-06-30
study_section: ZRR1-RI-8(01)
subproject_number: 7400
contact_pi_person_id: 7042565
contact_pi: LANE, ANDREW N
other_pis: Not Applicable
congressional_district: 03
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The primary aims of the Core D facility are to provide infrastructure and support for structural analysis and metabolomics of cancer cells and tissue and for producing proteins in high yield suitable for NMR analysis. This includes stable isotope labeling strategies including 15N and 13C precursors. Our goals continue to be to streamline both data collection and analysis.


application_id: 7382008
project_number: 5P20RR018733-04
project_title: COBRE: LOUISVILLE RES FOUND INC: CORE C: MOLECULAR MODELING FACILITY
administering_ic: NCRR
award_notice_date: 2006-07-27
opportunity_number: RFA-RR-02-007
application_type: 5
activity_code: P20
ic: RR
serial_number: 018733
project_start_date: 2006-07-01
project_end_date: 2007-06-30
study_section: ZRR1-RI-8(01)
subproject_number: 7399
contact_pi_person_id: 7821204
contact_pi: TRENT, JOHN O
other_pis: Not Applicable
congressional_district: 03
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The goals of the COBRE in Molecular Targets Molecular Modeling Core Facility have not changed. The Molecular Modeling Core Facility operated by Dr. John Trent is a state-of-the-art molecular modeling facility that has the capability of providing models based on structural data obtained from either X-ray crystallographic or NMR studies. In particular this facility has provided important molecular modeling services for Projects I II III and IV. Using homology modeling and virtual screening of potential inhibitors Dr. Trent has made very important contributions on a collaborative basis to members of each MT-COBRE project. This facility is located within the Brown Cancer Center. The capabilities of the facility include techniques such as explicitly solvated molecular dynamics homology modeling docking virtual screening ESP calculations and conformational searching.


application_id: 7382007
project_number: 5P20RR018733-04
project_title: COBRE: LOUISVILLE RES FOUND INC: CORE B: MICROARRAY FACILITY
administering_ic: NCRR
award_notice_date: 2006-07-27
opportunity_number: RFA-RR-02-007
application_type: 5
activity_code: P20
ic: RR
serial_number: 018733
project_start_date: 2006-07-01
project_end_date: 2007-06-30
study_section: ZRR1-RI-8(01)
subproject_number: 7398
contact_pi_person_id: 1969307
contact_pi: ZACHARIAS, WOLFGANG
other_pis: Not Applicable
congressional_district: 03
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The Microsequence Array Core Facility is located in the Baxter II Biomedical Research Building one block from the Brown Cancer Center. This facility contains an Affymetrix Genechip instrument which is available to all MT-COBRE members. Plans are underway for the development of a tissue array component of this facility as well. The Microsequence Array Facility is under the direction of Dr. Wolfgang Zacharias and has been fully operational for the past three and one-half years. It contains a full-time staff member Sabine Waigel who provides technical assistance in sample processing hybridization and data analysis. The Microsequence Array Core has a close relationship with the Laser Capture Microscopy facility in the Department of Pathology and a newly established Tumor Bank in the Brown Cancer Center. This allows the preparation of samples with known pathologic characteristics and appropriate control specimens. Dr. Zacharias is available for assistance with experimental design and data analysis. In March 2005 the new high-resolution Affymetrix Scanner 3000 upgrade was purchased and installed. This upgrade now allows us to use the newest generation of high-density whole genome v2.0 arrays for human or mouse for all COBRE investigators. Also several software/data analysis workshops were organized and held on campus for training of microarray technology user


application_id: 7382006
project_number: 5P20RR018733-04
project_title: COBRE: LOUISVILLE RES FOUND INC: CORE A:ADMINISTRATIVE CORE
administering_ic: NCRR
award_notice_date: 2006-07-27
opportunity_number: RFA-RR-02-007
application_type: 5
activity_code: P20
ic: RR
serial_number: 018733
project_start_date: 2006-07-01
project_end_date: 2007-06-30
study_section: ZRR1-RI-8(01)
subproject_number: 7397
contact_pi_person_id: 1898718
contact_pi: MILLER, DONALD M
other_pis: Not Applicable
congressional_district: 03
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. Core A the Administrative Core is responsible for the day-to-day operation of the Molecular Targets Center of Biomedical Research Excellence (MT-COBRE). Core A manages the scientific and administrative aspects of the COBRE. In collaboration with the Administrative Assistant Drs. Miller and Eaton are responsible for oversight of all administrative aspects of the COBRE. Several important changes have been made during the first three years of the MT-COBRE. Three of the five original investigators have received NIH funding during that period. Dr. Robert Mitchell Dr. Jason Chesney and Dr. Binks Wattenberg have received NIH R01 grants. This funding has provided an opportunity to recruit additional faculty to the MT-COBRE. We have been very fortunate to identify several outstanding candidates for the program.  Dr. Chi Li has joined the program from the University of Pennsylvania. Dr. Geoffrey Clark will join the program in July from the National Cancer Institute at the National Institutes of Health. Dr. Venkatakrishna Jala who has been a postdoctoral trainee at the University of Louisville will also soon join the program.  We have identified two outstanding recruits for the single remaining position. Dr. Qiutang Li has been a postdoctoral fellow at the Salk Institute in San Diego. Dr. Vishwa Dixit is being recruited from the National Institute on Aging in Baltimore. We are making offers to both of these individuals. If we are fortunate enough to attract both candidates we will use University funds to support the recruitment of one individual and use COBRE funds for the second. In concert with these recruitments we have also identified three outstanding experienced mentors: Dr. James Lillard Dr. Douglas Dean and Dr. Hari Bodduluri.


application_id: 7382005
project_number: 5P20RR018733-04
project_title: COBRE: LOUISVILLE RES FOUND INC: P5: CHROMOSOME SMC5-6 REGULATED BY SUMOYLATION
administering_ic: NCRR
award_notice_date: 2006-07-27
opportunity_number: RFA-RR-02-007
application_type: 5
activity_code: P20
ic: RR
serial_number: 018733
project_start_date: 2006-07-01
project_end_date: 2007-06-30
study_section: ZRR1-RI-8(01)
subproject_number: 7396
contact_pi_person_id: 8139941
contact_pi: YE, HONG
other_pis: Not Applicable
congressional_district: 03
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The structural maintenance of chromosome (SMC) proteins which are evolutionarily conserved from prokaryotes to eukaryotes is essential for higher-order chromosome organizations and functions. Six members of SMCs have been found in eukaryotes from SMC1 to SMC6 which form three distinct complexes each with a unique function. SMC5 and SMC6 interact with each other and associate with non-SMC elements to form the SMC5-6 complex that is essential for both DNA replication and the repair of DNA damage. Under normal conditions SMC5-6 is located at repetitive rDNA and telomere and responses for DNA replication and thus for cell survival. In addition when DNA is damaged by UV radiation or DNA damage reagents SMC5-6 is translocated to the DNA damage site as a response to DNA damage repair.    SMC proteins are organized into five domains: an N-terminal head domain a long coiled-coil helix a hinge domain another long coiled-coil helix and a C-terminal head domain. The N- and C-terminal head domains associate together to form an ATPase head domain. The long coiled-coil helices associate together to form the coiled-coil arm. The hinge domain dimerizes to form the hinge of the complex. The size and overall conformation of the SMC complexes make the study of the full-length proteins by crystallographic analysis difficult. However the SMC proteins have conserved domains that can be assembled independently suggesting that it will be possible to examine the structure of the individual domains and glean information on how structural changes in these conserved domains are linked to discrete functions for the different SMC family members.


application_id: 7382004
project_number: 5P20RR018733-04
project_title: COBRE: LOUISVILLE RF INC: P4: [RECRUIT EXPECTED TO COME 06/2006]
administering_ic: NCRR
award_notice_date: 2006-07-27
opportunity_number: RFA-RR-02-007
application_type: 5
activity_code: P20
ic: RR
serial_number: 018733
project_start_date: 2006-07-01
project_end_date: 2007-06-30
study_section: ZRR1-RI-8(01)
subproject_number: 7395
contact_pi_person_id: 9246960
contact_pi: JALA, VENKATAKRISHNA R
other_pis: Not Applicable
congressional_district: 03
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The PI and project title attached to this SPID (0004) former Project 4 has not been entered here because the position is currently vacant. Dr. Venkatakrishna Jala of the University of Louisville has been recruited for this position and will begin work in June 2006. The former PI for Project 4 Dr. Koslowski left the COBRE nearly 2 years ago to refocus his investigations. No narrative is entered here for him because he has not been on the COBRE during this reporting period.


application_id: 7382003
project_number: 5P20RR018733-04
project_title: COBRE: LOUISVILLE RES FOUND INC: P3: [RECRUIT EXPECTED TO COME 07/2006]
administering_ic: NCRR
award_notice_date: 2006-07-27
opportunity_number: RFA-RR-02-007
application_type: 5
activity_code: P20
ic: RR
serial_number: 018733
project_start_date: 2006-07-01
project_end_date: 2007-06-30
study_section: ZRR1-RI-8(01)
subproject_number: 7394
contact_pi_person_id: 1923480
contact_pi: WATTENBERG, BRIAN W
other_pis: Not Applicable
congressional_district: 03
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The PI and project title attached to this SPID (0003) former Project 3 has not been entered here because the position is currently vacant. Dr. Geoffrey Clark of the NIH has been recruited for this position and will be here in July 2006. The former PI for Project 3 Dr. Brian Wattenberg is no longer on the COBRE. Please see discussion of Dr. Wattenberg's ongoing activities and progress under Research Highlights in this report. Nothing is entered here because he has not been on the COBRE during this reporting period.


application_id: 7382002
project_number: 5P20RR018733-04
project_title: COBRE:LOUISVILLE RES FOUND INC: P2: [CHI LI (SPID 0013) ON SINCE 02/01/06]
administering_ic: NCRR
award_notice_date: 2006-07-27
opportunity_number: RFA-RR-02-007
application_type: 5
activity_code: P20
ic: RR
serial_number: 018733
project_start_date: 2006-07-01
project_end_date: 2007-06-30
study_section: ZRR1-RI-8(01)
subproject_number: 7393
contact_pi_person_id: 6950638
contact_pi: LI, CHI
other_pis: Not Applicable
congressional_district: 03
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The PI and project title attached to this SPID (0002) is entered under Chi Li SPID 0013. The former PI for Project 2 Robert Mitchell is no longer on the COBRE. Please see discussion of Dr. Robert Mitchell's ongoing activities and progress under Research Highlights in this report. Nothing is entered here because he has not been on the COBRE during this reporting period.


application_id: 7382001
project_number: 5P20RR018733-04
project_title: COBRE: LOUISVILLE RES FOUND INC: P1: GLYCOLYSIS AND NEOPLASTIC GROWTH
administering_ic: NCRR
award_notice_date: 2006-07-27
opportunity_number: RFA-RR-02-007
application_type: 5
activity_code: P20
ic: RR
serial_number: 018733
project_start_date: 2006-07-01
project_end_date: 2007-06-30
study_section: ZRR1-RI-8(01)
subproject_number: 7392
contact_pi_person_id: 1923745
contact_pi: CHESNEY, JASON A
other_pis: Not Applicable
congressional_district: 03
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. During the past 12 months we have examined the metabolic and neoplastic requirements of PFKFB3 for ras transformation using a combination of siRNA and heterozygote genomic deletion technologies. We find that PFKFB3 expression is selectively necessary for the control of glycolytic flux in cells transformed with ras and propose that pharmacologic inhibition of PFKFB3 may affect the survival and growth of neoplastic cells (see Subproject Progress in this report).


application_id: 7381934
project_number: 5P20RR017702-05
project_title: THE GENETIC BASIS OF CONGENITAL HEART DEFECTS (CHD)
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-02-003
application_type: 5
activity_code: P20
ic: RR
serial_number: 017702
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-A(02)
subproject_number: 7325
contact_pi_person_id: 8320904
contact_pi: TOMITA-MITCHELL, AOY
other_pis: Not Applicable
congressional_district: 03
department: DENTISTRY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF DENTISTRY/ORAL HYGN
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. Congenital heart disease (CHD) is one of the most common birth defects. Infants born with CHD often require multiple medical and/or surgical interventions and will nonetheless experience significant morbidity if not mortality. Despite their prevalence and clinical significance the etiology of CHD remains largely unknown. The pervading view is that the disease is heterogeneous and complex with bothenvironmental and inherited genetic risk factors. Mutations in a few cardiac development genes such as NKX2.5 GATA4 and TBX5 have been implicated as inherited risk factors. We propose using a novel highly sensitive mutation detection technology called Constant Denaturant Capillary Electrophoresis (CDCE) combined with High-Fidelity PCR (HiFi PCR) to determine whether mutations in each candidate gene are enriched in the patient population as compared to a large control population. This new technology enables the rapid and cost-effective analysis of large populations by pooling and screening DNA from 96 individuals at a time. The analyses of large populations are necessary to discover low frequency causal mutations and to quantitate low effect relationships between mutations and disease. Once enriched mutations are identified we will examine the potential biological effect of each mutation. These mutations may or may not lead to obvious changes in the encoded proteins via nonsense or missense mutations. Indeed there is increasing evidence that even translationally silent mutations and polymorphisms can have a phenotypic affect by altering pre-mRNA splicing. An additional layer of complexity is that a separate genetic mechanism for congenital heart disease has been proposed. Somatic mutations were recently identified in NKX2.5 and/or TBX5 in greater than 95% of hearts with septal defects. These mutations were identified within the septal defects and were not found in unaffected regions taken from the same heart indicating a somatic and mosaic nature for these mutations and suggest that these mutations are etiologic. Moreover multiple mutations as well as multiple haplotypes were observed within the same patient in a majority of these congenital heart disease patients. The occurrence of two or more somatic mutations in a gene is an exceedingly rare event and suggests a condition of extreme genomic instability reminiscent of that observed in cancer. In this proposal we will examine the genetic contribution of both inherited and somatic mutations in NKX2.5 GATA4 and TBX5 to cardiac malformations. Specifically we will: Specific Aim 1: Examine the contribution of molecular deficits in NKX2.5 GATA4 and TBX5 to the etiology of CHD. A. Test the hypothesis that mutations in NKX2.5 GATA4 and TBX5 increase risk for CHD using CDCE/HiFi PCR. B. Test the hypothesis that alternative splicing of NKX2.5 GATA4 and TBX5 confer an increased or decreased susceptibility to CHD. C. Determine if silent sequence variants observed in NKX2.5 GATA4 and TBX5 in CHD patients result in alternative splicing. D. Continue the ascertainment of a large well-characterized cohort of subjects with CHD Specific Aim 2: Examine the contribution of somatic mutations to the etiology of CHD. A. Test the hypothesis that somatic mutations in cardiac developmental genes are etiologic in CHD. B. Determine the mutation rate of cardiomyocytes during cardiogenesis in normal and malformed hearts. C. Use mutational spectrometry to discover primary mutagenic pathways in normal and malformed hearts. Our goal is to identify inherited mutations that are causally related to CHD determine the mechanisms by which they can increase risk of congenital heart disease and test the hypothesis that somatic mutations are etiologic in congenital heart disease. We will assess the biological significance of mutations found in these genes with the goal of identifying improved management strategies for the disease.


application_id: 7381933
project_number: 5P20RR017702-05
project_title: FACTORS ASSOCIATED WITH INTRAVENTRICULAR HEMORRHAGE IN THE PRETERM NEONATE
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-02-003
application_type: 5
activity_code: P20
ic: RR
serial_number: 017702
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-A(02)
subproject_number: 7324
contact_pi_person_id: 3121451
contact_pi: MAINOUS, ROSALIE O
other_pis: Not Applicable
congressional_district: 03
department: DENTISTRY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF DENTISTRY/ORAL HYGN
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The purpose of this research is to identify and describe factors that may impact or demonstrate the preterm infant?s response to noxious stimuli via three pilot projects to be undertaken within the next year. The primary grant proposal will identify cerebral blood flow dynamics and vital signs associated withnoxious stimuli in the preterm infant population of less than and equal to 32 weeks gestational age as a first step in developing a predictive model for intraventricular hemorrhage. Three specific pilot projects are proposed. First a study entitled ?Measurement Issues Related to Cerebral Blood Flow in the Neonatal Brain? will serve to provide the engineers on the major proposal with data on the use of Near Infrared Spectroscopy (NIRS) in the neonate. The second project ?Peak and Sustained Noise Levels in the NICU? will document an environmental variable that may be a confounder in the NICU. The third project to take place after the completion of projects one and two will be ?Correlation of Maternal and Infant factors with Incidence of IVH in one NICU?. This project will be a retrospective chart review to provide demographic and care variables that may be of interest in the predictive model.


application_id: 7381932
project_number: 5P20RR017702-05
project_title: THE EFFECT OF INTERNEURON LOSS ON MINICOLUMN STRUCTURE
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-02-003
application_type: 5
activity_code: P20
ic: RR
serial_number: 017702
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-A(02)
subproject_number: 7323
contact_pi_person_id: 8634532
contact_pi: SEELAN, RATNAM SATHIAGANA
other_pis: Not Applicable
congressional_district: 03
department: DENTISTRY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF DENTISTRY/ORAL HYGN
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The correct balance between excitation and inhibition is pivotal to the fundamental operation of the brain whether primary unimodal or heteromodal neocortex. Studies have suggested that minicolumns in the brains of patients with autism are narrower than those of controls with an altered internal configuration. (1) More specifically their minicolumns reveal less peripheral neuropil space and increased spacing among their constituent cells. The peripheral neuropil space is the conduit for among other things inhibitory local circuit projections. A defect in these GABAergic fibers may correlate with the increased prevalence of seizures among autistic patients. Unsurprisingly it has been argued that some of the behavior exhibited by autistic patients may be rooted in an imbalance between excitation and inhibition. A recent study shows that ?a single gene mutation can selectively alter the development of cortical interneurons in a region-and cell subtype-specific manner with deficits leading to long-lasting changes in circuit organization and behavior.? The mi(uPAR) were targeted with a mutation that affects interneuron migration. Anterior cingulate and parietal cortical areas contained 50 % fewer GABAergic interneurons compared with Wild Type (WT) littermates. No differences were found in visual or piriform cortex. There was a complete loss of parvalbumin (PV) subtypes with other classes remaining intact. GABAergic type cells known to be immunoreactive for PV include the basket and chandelier cells. The ability of a single gene mutation to cause a major loss in certain populations of specific GABAergic interneurons is especially significant in regards to genetic defects related to autism. The most prevalent genetic or environmental factor found among the first 100 cases in the South Carolina autism project is an abnormality of chromosome 15q that has three GABA receptor subunit genes. Furthermore mice of the uPAR strain demonstrated certain behaviors associated with autism which included a propensity for seizure disorders and both increased anxiety and timidity or recluse-like behavior. Thus we seek to determine whether the cortical minicolumn as represented by cell soma and apical dendrite bundles is narrower in the uPAR mouse than the WT. Secondly we will identify the distribution of GABAergic interneurons in the uPAR mice. Positive results would show that the loss of GABAergic interneurons can cause a narrowing of minicolumns similar to that found in the minicolumns of patients withautism. The manifestations of autistic like behavior in the uPAR mouse in conjunction with positive results from this study could promote its use as an animal model for autism. Specific Aim 1: To determine whether a reduction in GABAergic inhibitory interneurons is associated with the narrowing of pyramidal cell arrays. Specific Aim 2: To determine whether a reduction in GABAergic cells is associated with a narrowing between layer V apical dendrite bundles. Specific Aim 3: To determine the extent of GABAergic cell loss in barrel cortex in the uPAR mouse.


application_id: 7381931
project_number: 5P20RR017702-05
project_title: TOBACCO EXPOSURE BIOMARKERS AND MUTATIONS OF MSX1 AND IRF6 GENES IN PREGNANCY
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-02-003
application_type: 5
activity_code: P20
ic: RR
serial_number: 017702
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-A(02)
subproject_number: 7322
contact_pi_person_id: 1868682
contact_pi: MYERS, STEVEN RICHARD
other_pis: Not Applicable
congressional_district: 03
department: DENTISTRY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF DENTISTRY/ORAL HYGN
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. Exposure to tobacco smoke during pregnancy places the developing fetus at an elevated risk of severe outcomes related to smoke exposure. Most notably intrauterine growth retardation as well as decrease in birth weight have been measured as direct consequence of tobacco exposure in utero. However other harmful effects of tobacco smoking during pregnancy have also been identified including an elevated risk of birth defects. Of the thousands of compounds found in tobacco only a few have been studied in detail with respect to these changes. Most notably are the tobacco specific nitrosamines which have clearly been linked to experimental orofacial defects in animal models. Epidemiological studies have established a significant positive correlation between maternal smoking and an increased risk for orofacial clefts in humans. Studies analyzing the effect of tobacco constituents on mouse craniofacial development have provided clear evidence that the morphologic events can be disrupted by exposure to tobacco smoke. Specific genes related to the development of birth defects especially orofacial defects have been widely studied but the link between these genes and specific compounds in tobacco that may alter these genes expression and the metabolism and detoxification of specific tobacco carcinogens has not been carried out. In the proposed study we will recruit mothers that have smoked during pregnancy and investigate the relationship between smoking during pregnancy and the effects that tobacco exposure has in utero on specific genes related to birth defects. We will qualitatively and quantitatively assess exposure to tobacco and specifically to the tobacco specific nitrosamines NNN (N'-nitrosonornicotine) and NNK (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone) as well as benzo(a)pyrene by assessment of protein adducts to the compounds in maternal and fetal blood samples obtained at delivery. We will carry out genotyping to specific enzymes related to metabolic activation and deactivation of tobacco carcinogens CYP1A1 and microsomal epoxide hydrolase (MeH). We will isolate maternal and fetal DNA and characterize genes that are potentially related to the birth defects caused by tobacco smoke. In order to link tobacco exposure with specific genes related to birth defects we will examine and sequence two genes that are known to play a role in the etiology of orofacial defects the MSX1 and IRF6 genes. We will correlate mutations in the various genes with smoking status as well as biomarkers detected for the tobacco specific compounds. This link will assist in determining the relationships between smoking especially during pregnancy specific known teratogens in tobacco and mutations in specific genes that are known to be related to birth defects.


application_id: 7381930
project_number: 5P20RR017702-05
project_title: U-SHAPED DEVELOPMENT IN INFANT COGNITION AND PERCEPTION
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-02-003
application_type: 5
activity_code: P20
ic: RR
serial_number: 017702
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-A(02)
subproject_number: 7321
contact_pi_person_id: 8436880
contact_pi: CASHON, CARA HELEN
other_pis: Not Applicable
congressional_district: 03
department: DENTISTRY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF DENTISTRY/ORAL HYGN
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. Although development is traditionally thought to follow an increasing monotonic pattern in which infants or children improve with age closer examination indicates that infants may regress temporarily to a lower level subsequent to achieving a higher level of performance (Cashon & Cohen 2003 2004; Werker Fennell Corcoran & Stager 2002). In some cases this regression may be permanent (Pascalis de Haan & Nelson 2002). Such regression patterns certainly negate the traditional notion that development only entails steady improvement. Accordingly since these regressions are not predicted by theories when they do appear they are usually unexpected and not understood. Given the paucity of information in this area and the critical need for elucidating this process and its consequences for predicting developmental outcomes our overall GOAL for the proposed research is to investigate the underlying mechanisms involved in U-shaped patterns of development found during infancy. More specifically we will determine whether such patterns reflect a domain-general adaptive learning process that allows the infant to become more tailored to his/her environment or whether they reflect changes that are artifacts of the experimental task.  When infants display a U-shaped pattern of development it is often viewed as a result of reorganization (Werker & Tees 1984). We recently argued (Cashon & Cohen 2003; 2004) that such regressions are necessary as infants adapt to their environment. Infants must incorporate important information en route to becoming experts in the world around them. As a result of the reorganization process however infants may temporarily regress to a lower level. Two specific aims will address the GOAL of the proposed research which is to elucidate the underlying mechanisms involved in U-shaped patterns of development during infancy. Both aims will be met by testing infants in a visual habituation task whereby infants looking times are measured while they view a series of faces and moving objects. Aim 1 will build upon previous research indicating that infants face processing follows a U-shaped pattern. Aim 2 will empirically test the prediction that U-shaped development occurs prior to the development of an adaptive constraint. Aim 2 will be achieved by investigating infants perception of form-function correlations.  Aim 1 investigates the bases for the U-shaped pattern of development in infants processing of faces. In a previous set of studies we found that between 3 and 7 months of age infants processing of faces produces a U-shaped pattern with a drop in performance occurring at approximately 6 months of age (Cashon & Cohen 2004). We argue this regression is a necessary but temporary change resulting from overload as infants try to incorporate important information about faces. This notion is consistent with research in other areas of infant cognition and perception showing that when integrating new information infants regress to a lower level of processing (Cohen Chaput & Cashon 2002). Alternatively the apparent U-shape could be the result of 6-month-olds shifting their attention to focus exclusively on the eyes and eyebrows of a face. Aim 1 will investigate these two alternate hypotheses. It is predicted that 6 month olds will show evidence of overload and not of simply processing the eyes and eyebrows of a face.  Aim 2 investigates the bases for U-shaped pattern of development in infants processing of form-function correlations. Predictions of when U-shaped development will occur are lacking. We argue that U-shaped patterns occur just prior to perceptual of cognitive pruning. Accordingly we would expect infants to show a U-shaped developmental pattern in their processing of form-function correlations. Previous research by Madole and Cohen (1995) indicates that infants develop an adaptive constraint on their processing these correlations between 14 and 18 months of age. Based on our hypothesis we predict that a drop in performance occurs between these two ages. More specifically Madole and Cohen reported finding that 14-month-olds are sensitive to the correlation between the appearance (form) of a feature of an object and its function (within-feature form-function correlation) as well as the form of one feature and the function of another (between-feature form-function correlation). Importantly they also reported that 18-month-olds are sensitive only to the within-feature form-function correlation. Our specific prediction is that infants at approximately 16 months will regress and show no sensitivity to either correlation.


application_id: 7381929
project_number: 5P20RR017702-05
project_title: RING OR ZINC FINGER PROTEINS DURING GAMETOGENESIS AND EMBRYONIC DEVELOPMENT
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-02-003
application_type: 5
activity_code: P20
ic: RR
serial_number: 017702
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-A(02)
subproject_number: 7320
contact_pi_person_id: 6574851
contact_pi: LAN, ZI-JIAN
other_pis: Not Applicable
congressional_district: 03
department: DENTISTRY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF DENTISTRY/ORAL HYGN
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. Reproductive development and function are complex processes involving both genetically determined and physiological events. Identification of the critical genes involved in regulating these processes is necessary to characterize how these processes are coordinated. In particular the generation of mature gametes involves many steps of development and differentiation as well as the distinctive cellular process meiosis that are collectively termed gametogenesis. In general differentiation and development and other processes that lead to the acquisition and maintenance of a cellular phenotype are dependent on the differential and coordinate regulation of gene expression. However the regulation of gene expressioin many aspects of gametogenesis such as proliferation of spermatogonial stem cells signals for meiotic arrest and meiotic exit and spermiogenesis and cross-talk between germ cells and adjacent somatic cells are not clearly understood. In addition the roles of maternal and paternal genes in zygotic development are also not well defined. Identification and functional characterization of germ cell-specific molecules such as zinc finger proteins during gametogenesis and early embryonic development would advance our knowledge regarding gamete and zygotic development and will provide new leads for development of diagnostic reagents for reproductive diseases novel therapeutic medicines for the treatment of infertility gonadal cancers pre-natal death and novel contraceptive agents. The RING (Really interesting novel genes) finger is a specialized type of zinc finger proteins. It contains an evolutionarily conserved structure found in more than 300 proteins from the human genome database in which two loops of amino acids are pulled together at their base by eight cysteine or histidine residues that bind two zinc ions. There are two different variants the C3HC4-type and the C3H2C3-type which is clearly related despite the different cysteine/histidine patterns. These ring finger domains are found in two major classes of proteins: (1) transcriptional activators repressors or cofactors and (2) subunits of complexes that modulate chromatin. These proteins likely interact with other proteins participate in ubiquitination and play roles in cell growth control such as apoptosis tumorigenesis DNA damage repair and gene expression. In silico analyses have demonstrated that a large number of ring/zinc finger proteins with human homologs are expressed in the germ cells or early embryos indicating that these proteins may play a role in germ cell and zygotic development. Recent studies have shown that ring finger proteins zygote arrest 1 (Zar1) and NEURL are critical for zygotic development and male fertility and mammary gland maturation during pregnancy respectively. Ablation of another ring finger protein Siah1a also caused male infertility due to defects in meiosis. In addition another oocyte specific ring finger protein RFPL4 interacts with oocyte proteins and likely functions as an E3 ubiquitin protein ligase to regulate protein degradation and meiotic cell cycle progression. Therefore we are just in the beginning to understand the functional roles of these ring/zinc finger proteins during gametogenesis and early embryonic development. Having searched mouse and human genomic databases I found that seven uncharacterized genes likely play a role during gametogenesis and zygotic development as the expressed sequence tags (ESTs) of these genes are present in the cDNA libraries of mouse human germ cells or early embryos. I am particularly interested in five of these genes (named unknown 1-5) which are located in different mouse chromosomes and all have human orthologs. Unknown-1 -2 and -3 are C3HC4 ring finger proteins while unknown?4 and ?5 are C2H2 zinc finger proteins similar to zfp148 nanos2 and nanos3 which are required for male or female germ cell development. I will combine genetic molecular and cellular approaches to address whether these genes are involved in the gametogenesis and early embryonic development.


application_id: 7381928
project_number: 5P20RR017702-05
project_title: THE ROLE OF TFII-I TRANSCRIPTION FACTOR IN THE NEURAL TUBE CLOSURE DEFECTS
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-02-003
application_type: 5
activity_code: P20
ic: RR
serial_number: 017702
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-A(02)
subproject_number: 7319
contact_pi_person_id: 6065455
contact_pi: BAYARSAIHAN, DASHZEVEG
other_pis: Not Applicable
congressional_district: 03
department: DENTISTRY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF DENTISTRY/ORAL HYGN
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. Neural tube closure defects (NTDs) in particular anencephaly and spina bifida are common human birth defects. Risk of NTDs is inherited in humans but usually not as a single dominant or recessive gene. The incidence of NTDs varies with ethnic group socioeconomic group and time but remains on the order of 1 in 1000 births despite the use of folate supplementation in early pregnancy. Thus the use of mouse mutants and strains implicated in phenotype causation is very critical in our understanding of NTDs.  TFII-I is a transcription factor with multiple helix-loop-helix repeat domains. The TFII-I knockout mice generated in our laboratory display several phenotypic manifestations including NTDs. In an effort to establish the molecular basis of NTDs we will search for the downstream target genes regulated by the TFII-I family of transcription factors. We believe that certain set of genes in this category may be profoundly deregulated in the neural tube closure and are therefore most probably the immediate causal factors in NTDs.  The establishment of the developmental genetic basis of NTDs is important beyond the understanding it brings to neural tube closure itself. The identification of genes that regulate neural tube development allows further investigation of genetic interactions that may be causal to NTD conditions.


application_id: 7381927
project_number: 5P20RR017702-05
project_title: COBRE: UL: ADMIN: ALTERATION & RENOVATION
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-02-003
application_type: 5
activity_code: P20
ic: RR
serial_number: 017702
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-A(02)
subproject_number: 7318
contact_pi_person_id: 1861667
contact_pi: GREENE, ROBERT M
other_pis: Not Applicable
congressional_district: 03
department: DENTISTRY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF DENTISTRY/ORAL HYGN
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. This application requests $500000 for alterations and renovations to 2097 sq ft for three laboratories within the School of Dentistry.


application_id: 7381926
project_number: 5P20RR017702-05
project_title: COBRE: UL: P4: DVMT PROCESSES OF PITUITARY DIFFERENTIATION & MATURATION
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-02-003
application_type: 5
activity_code: P20
ic: RR
serial_number: 017702
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-A(02)
subproject_number: 7317
contact_pi_person_id: 2050006
contact_pi: MOORE, JOSEPH P
other_pis: Not Applicable
congressional_district: 03
department: DENTISTRY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF DENTISTRY/ORAL HYGN
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The sequence of events in sexual development is very important. An inappropriate hormonal environment can result in infertility of the adult male. Infertility affects approximately 15% of couples 40% are male infertility. An understanding of hormonal regulation of male sexual development may allow for early detection and prevention of infertility. The goals of this plan are to develop an understanding of regulation of the differential expression of the pituitary gonadotropins during maturation. There is data suggesting that pituitary adenylate cyclase activating polypeptide (PACAP) can differentially regulate the pituitary gonadotropins. PACAP increases the actions of gonadotropin releasing hormone (GnRH) and alone PACAP enhances the production of luteinizing hormone while decreasing follicle stimulating hormone expression. Our overall hypothesis is that during embryonic and early postnatal development the pituitary is exposed to very high levels of PACAP that selectively suppress FSH until the juvenile stage of sexual maturity. The specific aims of this proposal are: 1) To determine whether PACAP plays a role in the differential expression of the gonadotropin subunit genes during fetal pituitary development; 2) To determine if the rise in FSHb mRNA in immature male rats is related to weaning and is coincident with a change in PACAP expression; 3) To determine if pituitary cells from fetal and infant male rats are more responsive to PACAP than are cells from juvenile rats; and 4) To explore the developmental effects of PACAP through pituitary specific expression of the PACAP antagonist PACAP-(6-38). The proposed experiments will develop the PIs skills in the techniques of pituitary cell culture in situ hybridization laser capture microdissection single cell RT-PCR in situ hybridization Northern hybridization Southern hybridization and cDNA cloning. Successful completion of this proposal should provide insight into developmental regulation of gonadotropins and invaluable experience that the candidate can utilize to propagate a successful career.


application_id: 7381925
project_number: 5P20RR017702-05
project_title: COBRE: UL: P3: C-SKI TRANSCRIPTION OF NEURAL TUBE ONTOGENESIS: CRANIAL NEURAL
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-02-003
application_type: 5
activity_code: P20
ic: RR
serial_number: 017702
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-A(02)
subproject_number: 7316
contact_pi_person_id: 7842814
contact_pi: MUKHOPADHYAY, PARTHA
other_pis: Not Applicable
congressional_district: 03
department: DENTISTRY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF DENTISTRY/ORAL HYGN
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. Neural tube defects are amongst the most common birth defects occurring with a frequency of 1 in 1000 births. Although nearly 100 single gene mutations have been documented in animal models to cause neural tube defects few if any of these gene mutations have been characterized at a cellular and/or molecular level. It has been demonstrated that mutation in the gene encoding the protein c-ski (a regulator of gene transcription) in mice causes neural tube defects. Studies proposed within the present application will attempt to elucidate the cellular and molecular basis of c-ski gene inactivation in the genesis of neural tube defects. The hypothesis to be examined is that during the genesis of NTDs the cranial neural crest is a highly susceptible cellular target of c-ski loss of function. Loss of c-ski function as a transcriptional regulator may result in significant alterations in neural crest gene expression that will be assessed by microarray based molecular profiling of isolated neural crest cells. Attendant perturbations in neural crest formation migration proliferation or neural crest cell death will be examined in a unique animal model system that offers the ability to track the functional consequences of c-ski gene deletion (mutation) in labeled neural crest cells in intact animals. The studies proposed in the current application offer a novel approach to address genetic differences in susceptibility to NTDs as well as serve to initiate investigation at a mechanistic level of potential cellular and molecular targets of Ski during cranial neural tube morphogenesis.


application_id: 7381924
project_number: 5P20RR017702-05
project_title: COBRE: UL: P2: AN ANTIOXIDANT TRANSGENE PROTECT OFFSPRING FROM MATERNAL DIABETE
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-02-003
application_type: 5
activity_code: P20
ic: RR
serial_number: 017702
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-A(02)
subproject_number: 7315
contact_pi_person_id: 8340262
contact_pi: LIU, YE Q
other_pis: Not Applicable
congressional_district: 03
department: DENTISTRY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF DENTISTRY/ORAL HYGN
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. Prenatal environment greatly affects fetal programming and development. Various factors lead to low birth weight (LBW) which is associated with adult disorders such as type 2 diabetes. However the mechanism is still uncertain and controversial. We have started to establish LBW and maternal diabetic animal models to investigate how prenatal environment affects pancreatic beta cell programming and development. Methods: For LBW model we feed pregnant animals with low protein (LP 6% normal is 20%) diet and thiamine deficient diet; for diabetic model we use Bic mice (beta cell is destroyed by overexpression of calmodulin) and more than 90% pancreatectomy or streptozotocin-induced SD female rats as type 1 and Agouti/kk mice as type 2 diabetic models. We test fetal beta cell development and offspring pancreatic beta cell function. Results: We have obtained some results from 10 week old Wister rat offspring. In LP group (fed mother and pups with LP diet during pregnancy nursing and after nursing) body weight was only 30% of normal group; blood glucose was normal in these two groups; pancreatic islet protein and DNA contents were approximately 50% decreased; islet function glucose utilization and glucose oxidation were also decreased to 60% of normal. We tested thiamine deficiency in cultured the beta cell line INS-1 and found that a thiamine antagonist significantly inhibited tritium-thymidine incorporation into INS-1 cell DNA. In diabetic models hyperglycemia would be an important factor to affect beta cell; we tested cultured islets with high glucose and found that 3-day high glucose treatment decreased islet pyruvate dehydrogenase and pyruvate carboxylase activities but high free fatty acid only inhibited pyruvate dehydrogenase activity. Discussion: These results suggest many factors affect offspring beta cell function by different mechanisms. We will continuously test fetal beta cell development offspring beta cell function and specific gene expression.


application_id: 7381923
project_number: 5P20RR017702-05
project_title: TGF BETA & WNT SIGNALING: CROSSTALK DURING CRANIOFACIAL DEVELOPMENT
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-02-003
application_type: 5
activity_code: P20
ic: RR
serial_number: 017702
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-A(02)
subproject_number: 7314
contact_pi_person_id: 7839734
contact_pi: WARNER, DENNIS RAY
other_pis: Not Applicable
congressional_district: 03
department: DENTISTRY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF DENTISTRY/ORAL HYGN
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. Development of the craniofacial region in mammals is a complex and multifactorial process. The focus of our laboratory is to understand the underlying mechanisms involved in the control of craniofacial development since perturbations can lead to birth defects of the head and face. Many signaling molecules have been demonstrated to play critical roles in growth proliferation and differentiation of cells that populate the craniofacial region. Included in these are the transforming growth factor  (TGF) and Wnt signaling pathways. Our hypothesis in the current proposal is that the TGF and Wnt signaling pathways exhibit cross-talk leading to unique signaling outcomes not observed with either alone. This hypothesis was developed following our discovery via a yeast two-hybrid screen of developing craniofacial tissue that Smads the central mediators of TGF signaling interact with dishevelled (Dvl) the proximal cytosolic signaling protein in the Wnt signaling pathway. To examine the role of Wnt signaling in craniofacial development and in particular the Smad-Dvl interaction the following specific aims are proposed: 1) characterize the temporal and spatial expression of Wnt signaling components in developing murine embryonic craniofacial tissue and in cultured cells derived from developing craniofacial tissue through Western blot analysis and immunohistochemistry.  2) identify specific protein domains and post-translational modifications that mediate the interaction between Smad and Dvl. 3) examine the effect of the Smad-Dvl interaction on the outcome of signaling from both the TGF and Wnt signaling pathways through the use of transcriptional reporter assays and in vivo signaling through the use of specific inhibitors of TGF and Wnt signaling. These studies will further our understanding of the nature and role of the cross-talk between TGF and Wnt signaling in developing craniofacial tissue.


application_id: 7381922
project_number: 5P20RR017702-05
project_title: COBRE: UL: ADMIN CORE: MOLECULAR DETERMINANTS OF DEVELOPMENTAL DEFECTS
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-02-003
application_type: 5
activity_code: P20
ic: RR
serial_number: 017702
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-A(02)
subproject_number: 7313
contact_pi_person_id: 1861667
contact_pi: GREENE, ROBERT M
other_pis: Not Applicable
congressional_district: 03
department: DENTISTRY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF DENTISTRY/ORAL HYGN
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. DESCRIPTION (provided by applicant): The purpose of this application for a Center of Biomedical Research Excellence (COBRE) is to foster health-related research and increase the competitiveness of junior unfunded investigators at the Birth Defects Center at the UL School of Dentistry for independent funding. If funded this COBRE will augment and strengthen the biomedical research capacity at the Birth Defects Center through provision of flexible support to expand and develop biomedical faculty research capability. The program is led by an established biomedical research scientist well recognized for his extensive expertise central to the research theme of the proposal. The application seeks support for junior investigators from several complementary disciplines each of whom will be mentored by an established well-funded senior biomedical research faculty member recognized for his/her scientific expertise in the area of the junior investigator's research proposal. This approach is a critical assurance of success of this initiative. This application represents an integrated series of studies focusing on two common themes - molecular mechanisms of birth defects and cellular signal transduction - that encompass a number of diverse scientific disciplines. Faculty from the Schools of Dentistry Medicine Nursing Engineering and the College of Arts and Sciences representing a multiplicity of scientific disciplines present a multifunctional approach to questions of the molecular basis of developmental anomalies. This application if funded will substantially enhance the development of eleven young investigators with outstanding potential to develop into competitive independent and collaborative investigators. A detailed plan for their research career development has been formulated expectations and goals for achieving extramural support is outlined the extent of departmental and university support provided to these junior faculty is substantial clear and tangible evidence of institutional commitment has been documented and sufficient and adequate space and equipment resources for the conduct of the proposed studies exists.


application_id: 7381786
project_number: 5P20RR016481-06
project_title: WKU LEAD FACULTY
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-03-108
application_type: 5
activity_code: P20
ic: RR
serial_number: 016481
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-7(01)
subproject_number: 7180
contact_pi_person_id: 7326029
contact_pi: DAVIS, CHERYL D
other_pis: Not Applicable
congressional_district: 03
department: ANATOMY/CELL BIOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The INBRE Lead Faculty Representative from Western Kentucky University is responsible for overseeing institutional activities related to the program represents the institution on the steering committee and other INBRE-related subcommittees and serves as a liaison between the Administrative Core of the INBRE program and the faculty investigators and administrators at WKU. In this budget year the Lead Faculty Representative played a central role in the successful recruitment of a Neuroscientist to the Department of Biology at WKU (Tenure-track Assistant Professor Position). The lead faculty representative was also successful in obtaining an NSF-EPSCoR Research Start Up grant to assist in providing set-up funds for the newly hired neuroscience assistant professor.The addition of this faculty position will allow WKU to strengthen its research capacity in the area of Neuroscience enabling the institution to more fully participate in the Kentucky INBRE research network.


application_id: 7381785
project_number: 5P20RR016481-06
project_title: FUNCTIONAL & MOLECULAR ANALYSIS OF LONG-TERM SLEEP DISRUPTION BY ETHANOL
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-03-108
application_type: 5
activity_code: P20
ic: RR
serial_number: 016481
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-7(01)
subproject_number: 7179
contact_pi_person_id: 7024822
contact_pi: CARDEN, WILLIAMS B
other_pis: Not Applicable
congressional_district: 03
department: ANATOMY/CELL BIOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. Sleep perturbations by ethanol play a key role in the progression of alcoholism and are predictive of relapse. For some insomniacs the sedative effects of ethanol are the pathway to bedtime alcohol consumption and eventual abuse. Continued abuse of ethanol leads to long-term changes in neuronal sleep circuitry that last well beyond the cessation of ethanol administration. The overall goal of this project is to determine key molecular events that underlie cellular adaptation of sleep circuitry to alcohol and to correlate them with functional changes in sleep physiology. The thalamus is an integral participant in the generation of sleep/wake cycles and the brain rhythms that occur during sleep. One of the best understood of these rhythms is the thalamic spindle oscillation associated with Stage II sleep. In alcoholics spindle waves are diminished and are replaced with less-restful random eye movement (REM) sleep. Understanding the fate of spindle wave sleep is thus a vital question that directly relates to the reinforcement effects of ethanol since some alcoholics return to drinking in an effort to improve the quality of their sleep. The spindle waves generated by thalamocortical relay cells are the output of a complex network oscillation that is propagated throughout the brain. The engine that allows spindle waves to flow through the brain is a low threshold calcium current mediated by T-type calcium channels. Based on our previous studies thalamic T-type calcium channels appear particularly sensitive to ethanol exposure and the disruption of their function and/or availability may provide a cellular mechanism to explain why the sleep of alcoholics is disrupted. To test this hypothesis we are examining whether the electrophysiological properties and/or the relative expression of the thalamic T channels are affected in Long-Evans rats undergoing chronic ethanol self-administration.


application_id: 7381784
project_number: 5P20RR016481-06
project_title: IDENTIFICATION OF NON-RIBOSOMAL PEPTIDE SYNTHETASE FROM THE PERIODONATAL BACTER
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-03-108
application_type: 5
activity_code: P20
ic: RR
serial_number: 016481
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-7(01)
subproject_number: 7178
contact_pi_person_id: 8311899
contact_pi: RAJENDRAN, NARAYANAN
other_pis: Not Applicable
congressional_district: 03
department: ANATOMY/CELL BIOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. Oral bacteria have been implicated in endocarditis aspiration pneumonia osteomyelitis preterm low birth weight and cerebral infarction. These microbes (approx. 500 species) survive in a hostile environment where every organism has its own antimicrobial defense mechanism for colonization against each other or against host defense exudates. Oral bacterial play a major role in oral hygiene by forming a layer of protection as biofilm as well as causing pain tooth-loss morbidity and oral diseases. Periodontal disease is an infection due to the overgrowth of a finite number of specific oral bacterial. They are potential reservoirs for invasive pathogens which seed infections elsewhere in the body including cardiovascular diseases. Due to various defensive colonization processes operative within the oral entities there may be various antibiotic metabolites of quite specialized functions that are produced by these oral bacterial in unusual pathways called non-ribosomal peptide synthesis (NRPS). Although they are structurally different most of these peptides share a common mode of synthesis called multienzyme thiotemplate mechanism facilitated by peptide synthetases. They contain conserved motifs and are considered to be blueprints for peptide (antibiotic) synthesis. In the proposed study the genomic DNA of five periodontal/oral bacterial samples from the laboratory stock of the Center for Oral Health and Systemic Disease University of Louisville will be screened using peptide synthetase genomic probes. The proposed study uses no human subjects. As the result of this novel approach (i) the peptide synthetase producer bacteria can be identified and (ii) the NRPS-related peptide-antibiotic genes from these oral bacteria can be recognized. For the future these results will help to establish a comparative analysis with other oral bacteria and will yield a foundation for further expansion of this project using samples from clinical patients of periodontally healthy and non-healthy human subjects.


application_id: 7381783
project_number: 5P20RR016481-06
project_title: QSAR OF ADRENERGIC RECEPTOR ANTAGONIST
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-03-108
application_type: 5
activity_code: P20
ic: RR
serial_number: 016481
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-7(01)
subproject_number: 7177
contact_pi_person_id: 8536028
contact_pi: BAUTISTA, DEBRA
other_pis: Not Applicable
congressional_district: 03
department: ANATOMY/CELL BIOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The chloroplast of the common geranium Pelargonium hortorum contains the largest plastid chromosome of any land plant and has undergone numerous structural rearrangements (inversions and transpositions) and gene duplications making this a very active and dynamic genome. Our working hypothesis was that these extensive structural alterations are due to recombination events mediated by small dispersed repeat elements scattered throughout the genome. A collaborative effort was initiated with investigators at 3 other institutions (University of Texas/Austin University of California/Berkeley and Indiana University) and the DOE Joint Genome Institute and Lawrence Berkeley National Laboratory to sequence and annotate the entire geranium chloroplast genome. This effort has now been completed and is being submitted for publication. All likely genes have been annotated several gene losses have been documented and several families of repeat elements have been identified and mapped. These repeats are located at the borders of rearranged sequences and thus seem likely to mediate recombination events that would lead to rearranged genomes. Models have been proposed that account for the major genome rearrangements and can be tested by examining related species for intermediate states. In geranium one and possibly two transcriptional operons have been disrupted leading to a potential change in gene regulation. Despite the increase in size and complexity of the genome the gene content is similar to that of other flowering plants with the exception of a large number of pseudogenes. These findings have implications for understanding genome structural evolution and gene rearrangements in other circular genomes such as those of human mitochondria.


application_id: 7381782
project_number: 5P20RR016481-06
project_title: MPHETAMINE-INDUCED ACUTE WITHDRAWALS/REVERSIBLE DEPRESSION IN RATS
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-03-108
application_type: 5
activity_code: P20
ic: RR
serial_number: 016481
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-7(01)
subproject_number: 7176
contact_pi_person_id: 1885629
contact_pi: WHITE, WESLEY O
other_pis: Not Applicable
congressional_district: 03
department: ANATOMY/CELL BIOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. Moderate and high doses of amphetamine produce hypo-activity 20 hours after they are administered. This hypo-activity may indicate the presence of an acute withdrawal state and of a low-grade depression. The purpose of the research is to develop an animal model of acute withdrawal and to use it to investigate mechanisms and treatments. In the past year we have continued to develop procedures designed to provide converging evidence for the presence of acute withdrawal 20 hours after amphetamine treatment. At different times following amphetamine administration we have employed progressive ratio and conditioned place procedures in order to assess willingness to work for reward and to infer the nature of the internal state present. In order to identify the short dopaminergic changes that might be necessary to produce longer term amphetamine-induced hypo-activity we began to look at the ability of pre-treatment with dopamine receptor antagonists to block amphetamine induced effects. In order to begin to identify the molecular changes that mediate the proximate expression of amphetamine-induced hypo-activity we completed a ?small scale? micro array study: Twenty hours after treatment with either saline or amphetamine gene expression in the nucleus accumbens was assessed. Amphetamine administration supported a conditioned place aversion 20 hours later and an aversive internal state may have been present at that time. Amphetamine also compromised willingness to work for reward at different times during the first 24 hours following administration. The micro-array results identified a number of candidate genes that might be involved in the expression of acute withdrawal. Results are consistent with the presence of acute withdrawal 20 hours after amphetamine administration. Factors that may promote the occurrence of acute withdrawal have been identified. The research may yield an animal model with which acute withdrawal and low grade depression can be studied. issues in informatics.


application_id: 7381781
project_number: 5P20RR016481-06
project_title: A BUTTERFLY TRANSPOSON MUTAGENESIS SCREEN FOR THE STUDY OF WINGLESS SIGNAL
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-03-108
application_type: 5
activity_code: P20
ic: RR
serial_number: 016481
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-7(01)
subproject_number: 7175
contact_pi_person_id: 7015251
contact_pi: MARCUS, JEFFREY
other_pis: Not Applicable
congressional_district: 03
department: ANATOMY/CELL BIOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. My laboratory is developing techniques for genetic mapping and germ-line transformation in the buckeye butterfly Junonia (Precis) coenia. We are using these techniques to introduce a transposon carrying either an enhancer trap construct or a stable source of transposase into the different strains of butterflies and to use these strains to conduct a genome-wide enhancer trap mutagenesis screen. In this screen we are focusing on new insertions which either modify the orange bar phenotype associated with Wingless expression on the wings of the butterflies or which have enhancer trap expression patterns which show similarities to Wingless expression patterns. Flanking sequences of transposon insertions will be characterized and mutant genes will be identified by comparison to sequence databases. The effects of these mutations on wingless mRNA expression patterns will be examined by in situ hybridization. These new mutations will allow the further study of the Wingless signal transduction pathway in the butterfly wing and may permit us to identify previously unidentified members of the pathway. Further because this pathway plays a role in cancer formation in humans our findings may identify new genes that the broader research community can use as targets for the development of therapeutic agents in the treatment of cancer. We have also used computer simulation techniques to test previously proposed networks of genetic interactions for the formation of butterfly color patterns. Our simulations have revealed several weaknesses in these networks and have allowed us to propose more robust models for how these patterns form. Finally we are developing a molecular phylogeny of the genera Junonia and Precis which in combination with our improved models of color pattern formation will help us understand how color patterns have evolved during the diversification of these genera.


application_id: 7381780
project_number: 5P20RR016481-06
project_title: RNA-BASED MECHANISMS OF TRANSCRIPTION ELONGATION CONTROL
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-03-108
application_type: 5
activity_code: P20
ic: RR
serial_number: 016481
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-7(01)
subproject_number: 7174
contact_pi_person_id: 8534212
contact_pi: KING, RODNEY ALLEN
other_pis: Not Applicable
congressional_district: 03
department: ANATOMY/CELL BIOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The goal of this proposal is to build research capacity in the state of Kentucky by establishing a research program that is competitive at the RO1 level of federal funding. The project is designed to understand mechanisms of transcription elongation control and their evolution. We propose to characterize a unique mechanism of transcription elongation control originally discovered in the bacteriophage HK022. HK022 is a temperate phage of the lambda family that infects Escherichia coli. Most members of the lambda phage family use phage encoded proteins to promote gene expression by suppressing transcription termination. HK022 has dispensed with the requirement of an antitermination protein but relies on the direct interaction of sites in the nascent RNA transcript with the host RNA polymerase. These sites called put are located in each of the two early operons and are comprised of two stem and loops separated by an unpaired base. The structure of the sites i  s important for their function. Mutations that disrupt base pairing reduce antitermination and secondary mutations that reestablish base pairing restore terminator read through. Host mutants that prevent antitermination occur exclusively in a highly conserved zinc-finger domain located at the amino terminus of the beta prime subunit of RNA polymerase. These and other results suggest that the beta prime zinc finger recognizes put RNA and that this domain has a general role in transcription termination. By comparing the gene expression profiles of wild type E. coli with cells that carry mutations in the zinc finger we hope to identify cellular targets of this highly conserved domain. To increase our understanding of RNA-mediated antitermination and the importance of specific RNA structural elements we will identify and characterize additional examples of antiterminator RNAs.


application_id: 7381779
project_number: 5P20RR016481-06
project_title: NKU LEAD FACULTY
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-03-108
application_type: 5
activity_code: P20
ic: RR
serial_number: 016481
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-7(01)
subproject_number: 7173
contact_pi_person_id: 1893500
contact_pi: BARDGETT, MARK EDWARD
other_pis: Not Applicable
congressional_district: 03
department: ANATOMY/CELL BIOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The lead faculty will coordinate KY-BRIN activities within NKU and between NKU and other KY-BRIN organizations recruit new faculty into the BRIN program and support faculty and undergraduate research in the biomedical sciences. A part-time database/website administrator will also be hired. This person will develop and maintain databases pertinent to KY-BRIN research at NKU and a website that will provide information about the KY-BRIN program at NKU. This website will also serve as a resource for KY-BRIN researchers and students at NKU. The funding of this application will help strengthen the presence of the BRIN program at NKU and increase the awareness and involvement of NKU faculty and students in biomedical research. Methods: Provide release time and compensatory salary to PI to implement the goals listed above as well as recruit and maintain a qualified individual for the database/website administrator. Results: 1) The PI has attended all scheduled KY-BRIN related meetings since July 2006 and intends to attend other meetings (Ohio Valley Alliance for the Life Sciences) to network biomedical science at NKU into the larger regional biomedical science community. 2) A database/website administrator has launched the NKU KY-BRIN (ky-brin.nku.edu) website and maintains it on the weekly basis. 3) NKU will hire a tenure-track faculty member with research interests in animal behavior in the Department of Biological Sciences by May 2006. 4) The PI started an undergraduate neuroscience minor at NKU in Fall 2005. 5) The PI?s 2500 sq ft laboratory/animal facility was completely renovated (costs = approx. $60000) to support KY-BRIN-funded research. Discussion: We have made reasonable progress in increasing awareness of and faculty and student involvement in biomedical science especially in the area of neuroscience at NKU and expect to continue our pace of progress into year 3 of the grant.


application_id: 7381778
project_number: 5P20RR016481-06
project_title: MOLECULAR MECHANISMS OF ESTROGEN-REGULATED BONE RESORPTION
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-03-108
application_type: 5
activity_code: P20
ic: RR
serial_number: 016481
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-7(01)
subproject_number: 7172
contact_pi_person_id: 8475908
contact_pi: DEMOSS, DARRIN LEE
other_pis: Not Applicable
congressional_district: 03
department: ANATOMY/CELL BIOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The primary objective of this project is to enhance our understanding of the mechanisms of increased bone resorption which accompanies estrogen deficiency. Bone resorption parameters have been compared between control females six months of age ovariectomized females (OVX) females receiving hormone replacement therapy (HRT) and females receiving a calcium channel antagonists (Diltiazem Nifedipine Verapamil) or females receiving a combination of the two agents. As expected OVX rats displayed an increased rate of bone resorption from both skeletal compartments and HRT reduced that effect. The actions of the various antagonists were antagonistic to that of estrogen on the amorphous compartment and synergistic on the calcified compartment indicating differing mechanisms of action. The effects of the calcium channel antagonists on mean tail arterial pressure have proceeded as hypothesized demonstrating that all three classes of calcium channel antagonists significantly lowered blood pressure as compared to controls even when given in combination with HRT. ELISA assays designed to detect various bone degradation makers (deoxypyridinoline (DPD) pyridinoline (PYD) and helical peptide) in urine have provided an alternate avenue by which to monitor skeletal metabolism. OVX females display a significant increase in the excretion of DPD PYD and helical peptide indicating an increase in bone turnover while those receiving HRT were not significantly different from controls. The utilization of calcium antagonists decreases the excretion of DPD PYD and helical peptide indicating a decrease in bone turnover and suggesting a similar mode of action as estrogen. In order to determine the mechanism by which estrogen elicits this action in osteoblast-like cells (7F2 & UMR-106) experiments were carried out in an enriched media (OPTI-MEM) in the absence of estrogenic compounds (FBS & phenol red). This protocol did not alter the viability or morphology of the cells as compared to controls grown with FBS. Experimental results indicate that estrogen over a range of concentrations (0.1nM to 1.9mM) stimulates cell proliferation following 24 hr incubation demonstrating estrogen's osteoblastic activity. Our initial genomic studies suggest that estrogen up regulates the transcription of Transforming Growth Factor Beta Inducible Early Growth Response (TIEG) and osteoprotegerin (OPG). These experimental findings support the hypothesis of an antiresorptive role for estrogen in skeletal turnover.


application_id: 7381777
project_number: 5P20RR016481-06
project_title: CHARACTERIZATION OF PUTATIVE MAGNESIUM TRANSPORTING P-TYPE ATPASES
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-03-108
application_type: 5
activity_code: P20
ic: RR
serial_number: 016481
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-7(01)
subproject_number: 7171
contact_pi_person_id: 6945317
contact_pi: SCHULTHEIS, PATRICK JOHN
other_pis: Not Applicable
congressional_district: 03
department: ANATOMY/CELL BIOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. P-type ATPases comprise a large superfamily of proteins present in both prokaryotes and eukaryotes that transport inorganic cations and other substrates across cell membranes. Based on their conserved core sequences they have been classified into 5 subfamilies termed P1-P5. Members of the P1-P3 subfamilies have been well characterized using biochemical molecular biological and genetic techniques and include NaK-ATPases Ca-ATPases and HK-ATPases among others. P4-ATPases are expressed in all eukaryotes and include ~20 mammalian pumps that appear to function as aminophospholipid transporters. The most poorly understood P-type ATPases are those of the P5 subfamily which are expressed only in eukaryotes. Despite being retained over evolutionary time in organisms as diverse as yeast worms fish and humans little is known about their function. The overall goal of the current proposal is to carry out a basic characterization of the P5-ATPases in mice.  Specifically the aims are to 1) isolate full-length cDNA clones for each of the family members and determine their tissue distribution and membrane location 2) overexpress the novel P-type ATPases in the appropriate cell lines in order to assess their ion specificity and 3) determine their cellular and physiological roles in vivo using RNA interference (RNAi) and gene targeting technologies.  To date we have almost completed aim 1. Full-length cDNA clones of each of the five family members and their tissue distributions have been determined. This work was published in October of 2004 (see publications). Since the last progress report we generated antibodies to isoform specific peptides of each transporter and these are currently being characterized by Western blot analysis. We have also generated stable cell lines expressing V5-histidine and GFP tagged versions of the transporters. These cell lines are being used in immunofluoresence and colocalization experiments to identify the membrane location of each family member. This histidine tagged transporters will also be purified by nickel affinity chromatography and will be used in biochemical studies to determine the ion specificity of the transporters. Work has also begun on the construction of targeting vectors for two of the P5-ATPases Atp13a1 and Atp13a2.  An R15 grant entitled " has been submitted to NIH recently.


application_id: 7381776
project_number: 5P20RR016481-06
project_title: MECHANISMS OF TRANSCRIPTIONAL COORDINATION AMONG PHOSPHORYLASE KINASE GENES
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-03-108
application_type: 5
activity_code: P20
ic: RR
serial_number: 016481
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-7(01)
subproject_number: 7170
contact_pi_person_id: 6773495
contact_pi: RICE, NANCY AYERS
other_pis: Not Applicable
congressional_district: 03
department: ANATOMY/CELL BIOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. Phosphorylase kinase (PhK) is a key regulatory enzyme involved in the glycogenolytic pathway catalyzing the activation by phosphorylation of phosphorylase. The hexadecameric enzyme with subunit composition (alphabetagammadelta)4 serves to integrate hormonal metabolic and neural signals leading to the breakdown of glycogen stores in muscle and liver. Each subunit of PhK is encoded by a separate gene and multiple tissue specific isoforms exist for all of the subunits. While much work has been done to elucidate the biochemical regulation of PhK catalysis little information regarding transcriptional regulation of this complex oligomer is available. Our work seeks to elucidate those elements responsible for the temporal and spatial regulation of PhK gene expression by providing for the identification and functional analysis of all human alpha beta and gamma promoters. The proposed project has four aims directed at this goal. 1) The putative PhK promoter reg ions for all alpha beta and gamma isoforms will be identified through bioinformatic analysis of the human genome database and amplified by PCR. 2) The minimal sequence necessary to convey spatial and temporal gene expression will be determined for each promoter. 3) Key regulatory cis- and trans-acting factors will be identified for each promoter. 4) Microarray analysis will be performed on RNA from PhK deficient mice to identify novel proteins involved in coordinated gene expression. Knowledge gained from these aims will help determine how PhK expression is orchestrated to ensure that metabolic plasticity is modulated in response to changing energy demands.


application_id: 7381775
project_number: 5P20RR016481-06
project_title: GENETIC & METABOLIC ADAPTATION BY SALMONELLA TO THE NATURAL ENVIRONMENT
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-03-108
application_type: 5
activity_code: P20
ic: RR
serial_number: 016481
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-7(01)
subproject_number: 7169
contact_pi_person_id: 7614787
contact_pi: BARTON, HAZEL A
other_pis: Not Applicable
congressional_district: 03
department: ANATOMY/CELL BIOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. Salmonella is generally considered a low-frequency commensal and low-grade pathogen with very limited ability to survive long term in the environment outside of a host organism. Recent work has identified a constellation of interactive metabolic functions shared by all Salmonellae but absent from its nearest relative E. coli. The constellation of Salmonella-specific functions includes de novo synthesis of cobalamin (B12) use of B12 in degradation of ethanolamine and propanediol anaerobic respiration of tetrathionate to thiosulfate (ttr genes) and subsequent reduction to sulfite (phs genes) and sulfide (asr genes). All these functions would be used when Salmonella grows anaerobically on ethanolamine or propanediol in the presence of reducible sulfur compounds. Under these conditions Salmonella forms granules of mineral sulfur which it (but not E. coli) can later reduce by a process that requires the phs genes. While these functions may be important to pathogenesis we think it more likely that they suggest a significant lifestyle for Salmonella in particular soil environments. Our work has been geared to understanding whether there is an environmental niche for Salmonella and the potential impact that such an ecological niche will have on our understanding of the pathogenesis of this organism.


application_id: 7381774
project_number: 5P20RR016481-06
project_title: ANTIPSYCHOTIC DRUG ACTION AFTER HIPPOCAMPAL DAMAGE
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-03-108
application_type: 5
activity_code: P20
ic: RR
serial_number: 016481
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-7(01)
subproject_number: 7168
contact_pi_person_id: 1893500
contact_pi: BARDGETT, MARK EDWARD
other_pis: Not Applicable
congressional_district: 03
department: ANATOMY/CELL BIOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. Introduction: Deformations and functional alterations of the hippocampus a brain regions important in learning and memory have been reported in disorders such as schizophrenia and Alzheimer?s disease that are commonly treated with antipsychotic drugs. However it is unknown whether antipsychotic drugs can ameliorate the behavioral consequence of hippocampal dysfunction or conversely if hippocampal damage can undermine the behavioral and molecular pharmacology of antipsychotic drugs. The purpose of this grant is to address these issues by using a rat model of excitotoxic hippocampal damage.  Methods: The first aim of the grant has been to determine if and how acute or chronic antipsychotic drug treatment can reverse or reduce the effects of hippocampal damage on locomotor activity and spatial working memory. The second aim of the grant has been to determine if the effects of antipsychotic drug treatment on global gene expression are altered by hippocampal damage. The third aim has been to determine if and how hippocampal lesions alter the induction of transcription factors and other proteins by antipsychotic drug treatment.  Results: Between July 2005 and February 2006 we have focused our research on two proteins that serve as receptors for antipsychotic drugs the histamine3 (H3) and alpha2 (?2) adrenergic receptors. Our studies have found that antagonists for the former receptor can moderately improve spatial memory in rats with hippocampal damage while agonists for the latter site do not improve spatial memory in such animals. These data served as the basis for an R15 application submitted in 2005 by the P.I.. (The application received a score of 199 and was not funded). We have also characterized the effects of hippocampal lesions on global gene expression in the prefrontal cortex using microarray technology. A number of genes related to synaptic function were found to be altered in the prefrontal cortex of lesioned animals. We will continue these lines of research as well as study the effects of antipsychotic drugs on gene and protein expression in the frontal cortex and other brain regions.


application_id: 7381773
project_number: 5P20RR016481-06
project_title: UK BIOINFOMRATICS
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-03-108
application_type: 5
activity_code: P20
ic: RR
serial_number: 016481
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-7(01)
subproject_number: 7167
contact_pi_person_id: 8150729
contact_pi: STABEN, CHUCK
other_pis: Not Applicable
congressional_district: 03
department: ANATOMY/CELL BIOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. Along with my research assistants I work in the area of statistical bioinformatics. Prior to the development of microarrays biologists studied gene expression one gene at a time. Microarrays allow up to 46000 genes expression levels to be measured simultaneously. The huge amount of data generated in even simple microarray experiments requires sophisticated statistical approaches that are generally not available in standard statistical software packages.  Many statisticians working with microarray data propose almost incomprehensibly complex models that have few applications in practice. Our approach is different in that we assist many researchers by using standard approaches that we have developed that are generally quite successful. Many of the tools we have developed are available on our StatServer which is a web-based statistical software package that provides customized biostatistical and statistical bioinformatics procedures written by Yushu Liu who is an RA of mine supported by KBRIN/INBRE. Xu Ding who has partially supported by KBIN/INBRE worked on data management issues related microarray data. Many of these analyses have resulted in papers posters grant applications and/or funded grants.  In addition to providing statistical analysis of microarray data we write statistical methodology papers that explain appropriate statistical approaches for microarray data. One of our 2003 papers on statistical implications of pooling for microarray experiments is the ninth most downloaded paper of all time at BMC Bioinformatics. This year Hao Li has published a paper explaining the use of mixture models for microarray data and Hau Liu has a tentatively accepted paper suggesting improved methods of cluster analysis for microarray data.  Overall KBRIN/INBRE has been directly involved with generating over $10000000 in funded support over the last year involving bioinformatics at the University of Kentucky. These grants as well as KBRIN/INBRE fund all of my summer salary over 50% of my academic year salary four research assistants and two former research assistants who have now taken jobs.  In order to continue to expand the success we have had in statistical bioinformatics the Department of Statistics has offered a bioinformatics candidate an assistant professor position. Other faculty in the department are also becoming more involved in our statistical bioinformatics efforts. (SR Voss) My lab group is developing genome resources for model salamanders under an existing NIH-NCRR R24 Grant. KBRIN resources and technical support is allowing us to go beyond the database management and curatorial objectives of this funding mechanism. For example the KBRIN Apple Xserve G5 cluster (BIGAPPLE) has facilitated computational analyses that are allowing us to reconstruct genealogical relationships using DNA sequence form multiple nuclear loci. Such analyses are either difficult or impossible to accomplish on typical PC platforms. In a recent study we used BIGAPPLE to build gene trees from DNA sequences using the parallel processor version of MrBayes v3.04 (this program performs Bayesian phylogenetic analysis). This is a computationally intensive program that performs seamlessly and rapidly on the Xserve platform. We now depend upon BIGAPPLE to run the entire suite of phylogenetic and population genetic programs that we use in our studies. As another example KBRIN bioinformatics staff installed BLAT onto BIGAPPLE a program that can align very large DNA sequences that show nucleotide heterogeneity. We needed access to BLAT to facilitate a comparative gene mapping study where we are identifying the most likely genome positions in human that correspond to homologous DNA sequences that have been identified from salamander. Completion of this project will allow us to reconstruct the ancestral amniote genome structure which is needed to understand processes that have shaped the human genome. In addition this comparative information will allow us to cross-reference the salamander genome to the human genome for the purpose of identifying homologous genes. In general support from KBRIN is allowing Voss's group to be more than just a resource provider for NIH researchers; it is enabling their training and participation in bioinformatics.


application_id: 7381772
project_number: 5P20RR016481-06
project_title: COMPARING THE PROCESSES OF NEURAL DEVELOPMEANT & REGENERATION IN ZEBRAFISH
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-03-108
application_type: 5
activity_code: P20
ic: RR
serial_number: 016481
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-7(01)
subproject_number: 7166
contact_pi_person_id: 1884421
contact_pi: BILOTTA, JOSEPH
other_pis: Not Applicable
congressional_district: 03
department: ANATOMY/CELL BIOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The goals of this project are to examine the mechanisms involved in the development of neural circuits and compare these mechanisms of neural development to the mechanisms involved in regeneration in zebrafish. The purpose of this project is to determine whether neural regeneration is similar to the process of neural development or whether the two processes represent different mechanisms. The first specific aim of this work is to determine whether the recovery of the retina and tectum following retinal damage follows the same anatomical and physiological sequence found in normal development. The second specific aim is to examine whether environmental factors can modify the sequence of neural development and regeneration. To determine the importance of environmental signals in the developing and regenerating retina retinoic acid (RA) levels will be altered; RA is a known morphogen necessary for retinal development. The project's significance is that it will provide  a better understanding of the relationship between neural regeneration and visual development and has implications for eye health issues and for any eye disease in which retinal damage occurs.


application_id: 7381771
project_number: 5P20RR016481-06
project_title: INBRE COLLABORATION
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-03-108
application_type: 5
activity_code: P20
ic: RR
serial_number: 016481
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-7(01)
subproject_number: 7165
contact_pi_person_id: 7326029
contact_pi: DAVIS, CHERYL D
other_pis: Not Applicable
congressional_district: 03
department: ANATOMY/CELL BIOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. During this budget year a collaborative project was initiated with Dr. Abdelnaby Khalyfa and Dr. Nigel Cooper of the University of Louisville Health Sciences Center. This project utilizes Microarray (whole mouse genome) to analyze gene expression in the brains of mice infected with the parasitic pathogen Toxoplasma gondii. With this analysis it will be possible to determine the relative abundance of mRNAs expressed in mouse brain tissue and it will be possible to determine which genes are differentially expressed between T. gondii-infected mice maintained on a diet lacking vitamin E and selenium and those maintained on a diet containing elevated levels of these antioxidants. Although the major focus of our laboratory has been on genes of immunological relevance with microarray analysis other genes whose expression is influenced by diet will likely be identified.


application_id: 7381770
project_number: 5P20RR016481-06
project_title: EKU - LEAD FACULTY
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-03-108
application_type: 5
activity_code: P20
ic: RR
serial_number: 016481
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-7(01)
subproject_number: 7164
contact_pi_person_id: 10574352
contact_pi: CALIE, PATRICK JOSEPH
other_pis: Not Applicable
congressional_district: 03
department: ANATOMY/CELL BIOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. #


application_id: 7381769
project_number: 5P20RR016481-06
project_title: KBRIN -MOREHEAD STATE UNIVERSITY
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-03-108
application_type: 5
activity_code: P20
ic: RR
serial_number: 016481
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-7(01)
subproject_number: 7163
contact_pi_person_id: 9258139
contact_pi: MATTINGLY, BRUCE A
other_pis: Not Applicable
congressional_district: 03
department: ANATOMY/CELL BIOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The major of objective of this project is to increase biomedical research infrastructure and capacity at MSU. The specific aims are: 1) to increase biomedical NIH grant applications and funding; and 2) to increase the number of undergraduate students pursuing careers in biomedical research. Progress in the second year includes: 1) the MSU-INBRE steering committee consisting of researchers from molecular biology and behavioral neuroscience faculty continue to guide the development of biomedical research at MSU. 2) the MSU-INBRE seminar series continues with four seminars planned on neuroscience bioinformatics and genomics topics presented by scientists invited from the Harvard University and the University of Louisville. 3) Funds were expended to enhance the capabilities of fluorescent inverted microscope available to INBRE researchers; 4) Funds were made available to support undergraduate students (two biology two psychology) as INBRE Scholar-Assistants to work on biomedical research projects during the academic year and four previously funded students entered Ph.D. programs in biomedical sciences at the University of Louisville University of Kentucky and Purdue University; 5) Funds were provided to two grants development/ accountants staff members to attend professional Development workshops concerning the pre- and post-award administration of federal grants; 6) student and faculty biomedical researchers were funded to attend and present at research conferences including the Society for Neuroscience the Kentucky Academy of Science the joint Kentucky-Tennessee Bioinformatics Summit and meetings of the Louisville and Bluegrass chapters of the Society for Neuroscience; 7) Two biology faculty were selected as 2005 INBRE Summer Fellows to develop and submit new NIH R15 grant proposals. Together with the two supported INBRE principal investigators at MSU (Wesley White & Darrin DeMoss) four NIH R15/R01 grant proposals were submitted in September 2005. In addition to INBRE supported activities a scanning electron microscope was purchased with NSF funding the institution initiated an undergraduate research fellowship program which supported four additional students to work with INBRE researchers and the institution has received state and federal support to build a new health sciences research building. Thus as a direct and indirect result of the INBRE program we have made significant progress at MSU in the development of biomedical research and infrastructure.


application_id: 7381768
project_number: 5P20RR016481-06
project_title: BRIN: UL: GENOMICS CORE
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-03-108
application_type: 5
activity_code: P20
ic: RR
serial_number: 016481
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-7(01)
subproject_number: 7162
contact_pi_person_id: 1866398
contact_pi: COOPER, NIGEL G
other_pis: Not Applicable
congressional_district: 03
department: ANATOMY/CELL BIOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. University of Louisville Genomics Core  The shared centralized research core facility is designed to provide sequencing and gene-micro-array services to the University of Louisville and its KBRIN/INBRE affiliated institutions. We have continued to support the micro-array services of the Affymetrix facility in the Brown Cancer Center. The facility has performed analyses on 244 chips from 12 laboratories. Collaboration is on going with INBRE research teams. Specifically we are in the midst of performing gene array hybridization and analyses for with Dr. Wesley White at Morehead State University Dr. Cheryl Davis at Western Kentucky University and Dr. Mark Bardgett at Northern Kentucky University. This group is considering the development of a Collaborative Research Development Program application through Kentucky EPSCoR. This might provide pilot data that could lead to a NSF and/or an NIH collaborative application.  We have provided support for Drs. Dave Robinson & Mary Huff of Bellarmine University one of our outreach institutions to attend the week long Kentucky Proteomics Training Program at the University of Louisville to further their research skills & aims. Bellarmine has had six GenBank submissions this year.  NCBI GENBANK ACCESSIONS from Bellarmine University:  Steckler NK JM Lau and DL Robinson. 2004. Identification of ODZ3-like gene in Homo sapiens NCBI Accession AY736855: http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?db=nucleotide&val=52630904  Lau JM NK Steckler and DL Robinson. 2004. Detection in vervet monkey of the 3' untranslated CTG-repeat region associated with myotonic dystrophy. NCBI Accession Number AY640034: http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?db=nucleotide&val=4924 966  Lau JM NK Steckler and DL Robinson. 2004. Isolation of an ODZ3-like developmental gene from fallow deer. NCBI Accession Number AY640033: http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?db=nucleotide&val=4924 964  Lau JM NK Steckler and DL Robinson. 2004. Isolation of a developmental gene from Assamese macaque belonging to the mammalian ODZ gene family. NCBI Accession Number AY626784: http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?db=nucleotide&val=4847 041  Lau JM TM Brittian RB Burns and DL Robinson. 2004. Isolation of a developmental gene from lemur belonging to the mammalian ODZ gene family. NCBI Accession Number AY529203: http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?db=nucleotide&val=4279 780  Howard JM and S Wilt. 2004. Sus scrofa claudin-3 mRNA. NCBI Accession Number AY625258: http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?db=nucleotide&val=4837 875 .


application_id: 7381767
project_number: 5P20RR016481-06
project_title: BIOINFORMATICS CORE
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-03-108
application_type: 5
activity_code: P20
ic: RR
serial_number: 016481
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-7(01)
subproject_number: 7161
contact_pi_person_id: 7948398
contact_pi: ROUCHKA, ERIC CHRISTIAN
other_pis: Not Applicable
congressional_district: 03
department: ANATOMY/CELL BIOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. Students Supported  I. Elizabeth Cha (doctoral candidate) January 2005-present.  Elizabeth has been involved in research concerning the clustering alignment and mapping of large databases of biological data such as human ESTs. As part of her research she has looked at methods for parallelizing approaches to sequence alignment. One of her projects looked at the performance of different versions of the BLAST software including possible enhancements. This research was accepted as a paper and presented at the HICOMB 2005 conference. In November 2005 Ms. Cha successfully presented her dissertation proposal and passed her preliminary examination on methods for detecting and classifying pseudogenes. In addition Ms. Cha is currently responsible for the maintenance and update of the computers in the Bioinformatics Laboratory.  Ravishrikanth Gundlapalli (master's student) Summer 2004; Fall 2005.  Ravi spent the summer of 2004 and the fall of 2005 working on a front-end system for the design and storage of data pertinent to customized gene arrays. His system will allow researchers to design and analyze their own custom chips in a much quicker fashion than the currently implemented approach. Mr. Gundlapalli successfully defended his thesis work in December 2005.  Yamini RudraRaju (master's student) Spring 2006. Yamini will be spending the spring of 2006 on a research project in the bioinformatics laboratory. Yamini is the first student to participate in the joint EKU-UofL bioinformatics master's program and will be supported by the EKU INBRE subaward. Her research project will involve the computational design of degenerate primers.  Other Supported Staff Larissa Tiouliandina Summer 2005-present Larissa has been working closely with Dr. Eric Rouchka and Ms. Stephanie Dearing to develop a database to help track information gathered from the KBRIN-INBRE network including grants publications presentations honors and awards and student tracking information. The database system will have several levels of security for administrators Lead faculty external advisory members and individual researchers. A targeted release date has been set for late spring 2006.  Bioinformatics Theses and Dissertations  The following students have successfully completed master?s projects theses or dissertations at the University of Louisville within the past year with topics related to bioinformatics. KBRIN-affiliated faculty involved in the committees are listed. Abhijit Phatak. (2005). Using relational databases to analyze microarray probes and single nucleotide polymorphisms. Eric Rouchka advisor. Project defense date: August 2005.  Ravishrikanth Gundlapalli. Microarray Database Resource for Designing Custom Microarrays (2005). Eric Rouchka advisor. (Nigel Cooper committee member). Defense date: December 2005.   Molecular Modeling Resources  In October 2002 KBRIN and the Department of Biochemistry & Molecular Biology established a biomolecular modeling and graphics system for teaching and research purposes. A dual-processor Silicon Graphics Octane graphics workstation (reconditioned) running Irix 6.4 was purchased and connected to the university network. The SGI Octane is equipped with a large color monitor 1 MB memory 100 GB hard drive and a Crystal View 3-D system that allows viewing graphics in high-quality 3-dimensional images that can be manipulated with a mouse or cursor keys. Three-year licenses for the following software was purchased from Accelerys Inc.   Insight II 2002.1 (molecular visualization and analysis; control module for other software)  Biopolymer (construction of polypeptides carbohydrates and nucleic acids from building blocks)  Homology (builds a 3-D model of a protein from its amino acid sequence aligned to the sequence of a homologous template protein of known structure)  Modeler (automatically generates 3-D homology models of proteins; similar to Homology but more versatile)  Discover 1 & 2 and associated force fields (molecular dynamics programs)  Decipher (analysis of complex molecular structures and output from molecular dynamics simulations)  Binding Site Analysis (characterization and comparison of protein binding sites)  One year later the following modules were added (perpetual licenses) with partial support from KBRIN and Biochemistry:   Profiles 3D (data base searching for structural motifs in proteins for similarity analysis)  SeqFold (protein fold recognition to help identify protein function; analyzes structural similarity based on physical-chemical attributes of amino acids in the protein structure data bank PDB)  CHARMm (molecular dynamics calculations for macromolecules)  Search/Compare (compares conformations of different macromolecules)  In December 2006 after expiration of licenses purchased in 2002 we renewed the following modules and added some new modules. Perpetual licenses were purchased with the financial support of KBRIN Biochemistry the JG Brown Cancer Center and individual researchers in Biochemistry and the Cancer Center. We now have updated licenses for the following:   Insight II 2005.1  Biopolymer  Modeler  We also purchases perpetual licenses for:   ZDockPro (protein-protein docking from PDB files)  Delphi (rigorous calculation of electrostatic potentials for proteins and polynucleotides)  Ludi/CAP (fits molecules into the active site of a receptor by identifying complementary polar and non-polar groups from a library of commercially available small molecules)   Computer Resources  The Bioinformatics Lab currently has four students working on bioinformatics full-time (two Ph. D. and two masters). Two undergraduate students are working part-time in the bioinformatics lab and one high school student is working on a bioinformatics-related science fair project under the direction of Dr. Rouchka. Two additional masters students have been working in the bioinformatics lab during the past year.   There are three main servers maintained for use by KYBRIN investigators. They include the 16-node 32-cpu kybrin Beowulf cluster computer a dual-processor linux RedHat 9.0 server and a dual processor Windows Server 2003.   kybrin.louisville.edu  The 16-node 32 cpu Beowulf cluster (kybrin.louisville.edu) is the most heavily used of the systems. The use is mainly for bioinformatics research requiring parallel computation. Currently there are 45 users who have interactive login accounts. A 2.4 Terabyte RAID network attached storage (NAS) system is currently tied directly into the Beowulf cluster machine housed in the Dahlem supercomputing center. Currently 374 GB of the 2.4 Terabyte storage is used.  Research performed on the Beowulf cluster during the past year is described in the Research section. Upgrades to the kybrin.louisville.edu system this last year include the purchase of memory to expand the web server to 4 GB; a backup master node; and several hard drives. Each of these has been put into place to help minimize downtime of the system in case of a hardware failure.  Invitrogen License Server. In addition to the research performed the KYBRIN Beowulf cluster also acts as the University of Louisville license server for the statewide license for Invitrogen's Vector NTI and Vector XPression software. The usage over the past year:  The following table and two graphs show the usage of the Informax/Invitrogen software over the past three years. It must be noted that for 2004-2005 there is a chunk of missing data equivalent to about 3 weeks of usage. In addition the two heaviest users were excluded since they severely skew the data (pumping up the VectorNTI usage to over 93000 licenses granted). This data indicates that the overall usage increased at a rate of about 150% per year through 2005 mainly due to the VectorNTI package. However the sharp decline in the use of Expression indicates this is not a viable alternative for microarray data analysis. The sharp decline in usage in 2005-2006 can be attributed to two factors. This is a decline in the usage by the three major users of the software along with Invitrogen's September 15 2005 announcement of an Open Access Policy for Academic and Government researchers beginning with the VectorNTI v10.0 released 9/15/2005 thus effectively eliminating the need for a dynamic license server (and therefore the ability to accurately track usage).   Year Users VectorNTI AlignX BioPlot ContigExpress Expression Total Licenses 2002- 2003 76 5070 713 50 221 161 6215 2003-2004 93 7677 1171 78 634 114 9889 2004-20051 91 9848 886 26 643 4 11350 2004-20052 91 93469 886 26 64 4 94971 2005-2006 66 2416 660 26 405 4 3511  Table 1: Informax/Invitrogen Usage (University of Louisville Dynamic License Server).  1This data excludes the two highest users of VectorNTI. 2This data includes all users of all software packages.    Access Grid Node Server. The KYBRIN Beowulf cluster also serves as an Access Grid (AG) Node server. This server will allow for researchers across the state of Kentucky to participate in a remote discussion using relatively little resources ? basically a headset and a web camera. Nathan Johnson and Ed Birchler of the Dalhelm Supercomputer Center at the University of Louisville have been visiting various KYBRIN sites throughout the past year to set up individual clients and to assess the technical capabilities of each University.   kbrin.a-bldg.louisville.edu  This system is a dual-processor 2GHz AMD RedHat Linux based server used for a variety of web applications and development. There are currently five interactive logins for this system Some of the development performed on this server includes the MPrime primer design software and MySQL microarray database development. This server serves as a web server for information concerning the CECS 660-01 Introduction to Bioinformatics. In addition this system is used for administrative purposes including a GrantSlam server and for web applications requiring mailed forms and database input and querying.  From 6/12/2005 to 1/6/2006 there were a total of 374272 page hits to this server. The majority of these hits are listed in Table 2.   Description of Pages Number of Hits CECS 660 Introduction to Bioinformatics online Course Matherial 215867 University of Louisville Bioinformatics Research Group (BRG) 31853 CECS 302 Information Structures Course Material 23975 EMBOSS 5336 Bioinformatics Journal Club 2721 Local Bioinformatics Research Papers 1078 MPrime Multiple Primer Design 668  Table 2: Summary of majority of web hits for kbrin.a-bldg.louisville.edu.   medschsrv.spd.louisville.edu  This system is a dual-processor Windows Server 2003 system. There are two primary uses of this system: as a windows-based license server (including S+ 6.1 and ArrayAnalyzer 2.0) and as a database development tool using MS-SQL.   Conferences and Meetings  Fifth Virtual Conference on Genomics and Bioinformatics (10/25/2005-10/28/2005)  For the fourth consecutive year the access grid node at the University of Louisville broadcast the Virtual Bioinformatics Conference with around ten students and faculty tuning in at various times. This year Dr. Eric Rouchka gave a presentation on ?Statewide bioinformatics in Kentucky? The plan is to broadcast it again next year.  Kentucky Academy of Sciences (11/10/2005-11/12/2005)  This year KAS once again sponsored a session on Computer and Information Sciences with the emphasis on Bioinformatics applications. A total of ten oral presentations and four posters were presented. Three of the four undergraduate winners for oral presentations were advised by KBRIN sponsored faculty as were both of the graduate winners. The president and secretary for this session for 2006 were re-elected and both (Chuck Staben University of Kentucky; Eric Rouchka University of Louisville) are KYBRIN affiliated researchers.   Place Student School KBRIN Advisor 1st Undergrad Eren Turgay Univ. of Kentucky Jaromczyk 2nd Undergrad Wesley Asher Eastern Kentucky Bautista 3rd Undergrad Nathan Gilbert Morehead State N/A 4th Undergrad Lauren Stein Eastern Kentucky Bautista 1st Undergrad Poster Brianna Paisley Eastern Kentucky Bautista 1st Grad Josh Gilkerson Univ. of Kentucky Jaromczyk 2nd Grad Ravi Gundlapalli Univ. of Louisville Rouchka; Cooper  Table 3: KAS Computer and Information Science Section Winners.  The opening symposium for this year's Kentucky Academy of Sciences (KAS) was based on state-wide bioinformatics entitled ?Genomics & Bioinformatics: Research Resources & Programs in Kentucky.? This symposium included a panel discussion involving five KBRIN-INBRE researchers: Chuck Staben (University of Kentucky) Eric Rouchka (University of Louisville) Claire Reinhart (Western Kentucky University) Pat Calie (Eastern Kentucky University) and Mark Bardgett (Northern Kentucky University).  KAS held for the first time a session on Computer and Information Sciences with the emphasis on Bioinformatics applications. The president and secretary for this session for 2005 were elected and both (Chuck Staben University of Kentucky; Eric Rouchka University of Louisville) are KYBRIN affiliated researchers.  During April 1-3 2005 researchers from across the state of Tennessee and Kentucky will meet at Lake Barkley State Park in Cadiz Kentucky for a summit on bioinformatics. In addition to 15 talks and a poster session by researchers in Kentucky and Tennessee there were a number of well-respected invited speakers including: Chip Lawerence (Brown University) Martin Tompa (University of Washington) Paul Thomas (Applied Biosystems) Dan Gusfield (UC Davis) Seth Grant (Wellcome Trust Sanger Institute) Carey Phillips and Jean Thierry-Mieg (NIH). Over 160 people attended the summit with more than 80 coming from Kentucky with the majority having direct or indirect affiliation with KYBRIN. This conference is being sponsored in part by KYBRIN. Four members of the organizing committee Nigel Cooper (UofL) Eric Rouchka (UofL) Stephanie Dearing (UofL) and Chuck Staben (UK) are directly affiliated with KYBRIN while a fifth Daniel Goldowitz (UT Memphis) is on the external advisory board.  UT-ORNL-KBRIN Bioinformatics Summit 2006 (4/21/2006-4/23/2006)  During April 21-23 2006 researchers from across Tennessee and Kentucky will once again gather in Lake Barkley State Park in Cadiz Kentucky for the Bioinformatics Summit. This year?s speakers include Hamid Bolouri (Institute for Systems Biology) David Galas (Batelle) Isaac Kohane (Harvard) Dan Masys (Vanderbilt) David Schwartz (NIEHS) Robert Kavlock (EPA) Wyeth Wasserman (Univ. of British Columbia) and Jack Keene (Duke). There will be several workshops on topics such as bioinformatics education proteomic analysis microarray analysis and imaging atlases as well as sessions on Genes and the Environment The Regulome and Clinical Bioinformatics.  Research  Bioinformatics Research Group (BRG)  The Bioinformatics Research Group (BRG) has been active since mid-2001. The BRG brings together researchers from across the University of Louisville's campus in order to promote collaboration between researchers in the School of Public Health Health Sciences and Computer Engineering and Computer Science. The BRG holds meetings twice a month once at the Speed School of Engineering and once at the Health Sciences Campus. The main focus of the BRG is on the development of databases applications and meta-analysis of microarrays. The BRG website is being hosted at: http://kbrin.a-bldg.louisville.edu/brg/  Research Projects  The following research projects have been active within the past year. In addition these projects have used computing resources made available through the KBRIN-INBRE grant.  Detection of Tandem Repeats in the Zebrafish Genome (E.C. Rouchka University of Louisville) The zebrafish geneome is highly polymorphic with single nucleotide polymorphisms (SNPs) occurring at an average of once every 200 bases. However a high density genetic map of the genome does not currently exist. Due to the availability of a rough draft assembly of the zebrafish genome and the underlying trace data it is now possible to construct such a map by looking at regions that are more susceptible to polymorphisms. One such region is tandemly repeated elements which have been known to cause disease (such as Fragile X Myotonic Dystrophy and Huntington's Disease in humans) due to variations in the copy number. Computational detection of these tandemly repeated regions and design of primer pairs to amplify these regions can help molecular biologists determine which of these regions have observable polymorphisms in a population and can therefore be used as genetic markers. A total of 19845 regions containing a repeat of length greater than four with a copy number greater than 10 and a total length of 250 base pairs or less have been detected. Currently we are working with a molecular biology lab in determining whether or not a subset of the pentamer repeats indicates polymorphisms within the population.  MiDaR: Microarray Database Resource (EC Rouchka J Hornsby R Gundlapalli R Jones D-J Chang S El-Hadik A Desoky A Elmaghraby NGF Cooper University of Louisville) Microarray technology has the potential to yield a vast amount of gene expression data. MiDaR is multifaceted project to explore the implementation of a database management and analysis resource for both custom microarrays (both cDNA and oligo based) and commercial microarrays (including Affymetrix and Agilent).    The various aspects of MiDaR include: Custom Chip Design (Gundlapalli Rouchka and Cooper) This part of the project deals with the physical layout of customized microarrays allowing the user to determine which genes/gene groups to place on a given chip as well as designing the oligos and/or primer products to represent each gene. Each of these layouts can be stored in a database and edited at a later time.  Management of Microarray Data (Hornsby Jones Rouchka and Chang) Object-relational database schemas for the management of microarray data from different sources is considered in the portion of MiDaR. Data from different sources will be able to be interchanged for analysis purposes.  Relation of Microarray Data to Biological Information (Jones Rouchka) MiDaR will also allow the user to associate microarray information with other relevant genetic information including related gene and protein structures homologous sequences and genetic regulatory pathways both known and unknown. This portion of MiDaR will potentially be tied into other sources of data as well including proteomics and metabolomics.  Data Analysis (Rouchka El-Hadik Desoky Elmaghraby) The analysis of the differential expression of genes relative to a given cell type stimulus or time point is the most desired information for a biologist. Portions of MiDaR are concerned with taking the data stored within the data management system analyzing it and placing the results of the experimental comparison back in the database. The analysis are performed using customized routines connected with R Bioconductor and Matlab bioinformatics.   Multiple Primer Design (EC Rouchka; A Khalyfa; NGF Cooper University of Louisville) Motivation: Enhancements in sequencing technology have recently yielded assemblies of large genomes including rat mouse and human. The availability of large-scale genomic and genic sequence data coupled with advances in microarray technology have made it possible to study the expression of large numbers of sequence products under several different conditions in days where traditional molecular biology techniques might have taken months or even years. Therefore to efficiently study a number of gene products associated with a disease pathway or other biological process it is necessary to be able to design primers en masse rather than using a time consuming and laborious gene-by-gene method. As a result we have developed an integrated system MPrime in order to efficiently calculate primer pairs for multiple genic regions based on a keyword gene name or accession number within the rat mouse and human genomes. Results: A set of products created for mouse housekeeping genes from MPrime-designed primers has been validated using both PCR-amplification and DNA sequencing. These results indicate MPrime accurately incorporates standard PCR primer design characteristics to produce high scoring primer pairs within the mouse rat and human genomes.  EST Clustering and Analysis (IE Cha EC Rouchka DJ Chang University of Louisville) The availability of comparative genome sequence data as well as expressed sequence tag data (ESTs) has made it possible to study gene structure within humans and comparative genomes such as mouse and rat. In this project we are interested in exploring efficient methods for mapping EST sequences to their genomic counterparts for the purpose of clustering and comparing gene structure and alternative splicing in multiple organisms. We are currently exploring the use of cluster and grid technologies for this purpose.  Motif Detection Using Heuristic Algorithms (CT Hardin EC Rouchka University of Louisville) Conserved patterns (motifs) are useful for both classification purposes and for understanding relations between sequence structure and function of proteins. We are working to identify new heuristic-based algorithms to identify these motifs in unaligned protein or nucleotide sequences. The goals of the research are two fold: 1.) find patterns that are not discovered using other methods and 2.) improve the computational efficiency of existing algorithms. Student research.  (Dr. Robert Gray and Mary Constantino University of Louisville)  Mary Constantino made a homology model of a BTB binding domain from Drosophila based on a similar domain from humans.  She was able to rationalize site directed mutation experiment based on the model in her Ph.D. thesis.  Faculty research.  (Joint efforts with Robert Gray University of Louisville) Dr. Gray has done homology modeling for Dr. Ramos and protein-protein docking and graphics for Dr. Wang. In addition a few other faculty members have indicated an interest in homology modeling once the licenses have been renewed.  Educational Opportunities  Course Related Work  CECS 660 Introduction to Bioinformatics. During 2005-2006 the Introduction to Bioinformatics Course CECS 660-01 had nine students were pre-enrolled for the course including students from the Health Sciences Campus Speed School of Engineering and the Business School.  CECS 660-01 will be continued to be offered every spring while the bioinformatics journal club will likely be offered more on an interest basis. For the spring of 2006 there are eight students pre-enrolled including two students from the biostatistics department one from the medical school one visiting student from Eastern Kentucky University and four from the Speed School of Engineering.  Biochem 670 (Protein Structure and Function). Eighteen graduate students have taken the course in the last 3 years. Sixteen were from BMB 1 from Biology and 1 from Microbiology/Immunology. A 2-hr lecture on molecular modeling was added to the course focusing mostly on homology modeling and sequence alignment. Most of the students spent ~1 hour running a standard tutorial on the Modeler software where they constructed a model of a serine protease based on trypsin and chymotrypsin.  Joint Master's Program in Bioinformatics. The joint Master's program between the University of Louisville and Eastern Kentucky University (EKU) is progressing with the first student Yamini Rudraraju spending the spring of 2006 working on a research project in the KBRIN bioinformatics lab. More students are in the pipeline and there will be on average 1-3 students per year.  Training  Dr. Gray (with support from BMB) has attended three 2-day training work-shops at the Accelrys headquarters north of San Diego. These workshops are: Introduction to Life Science Modeling with Insight II Homology-Based Protein Design and CHARMm: Molecular Mechanics and Molecular Dynamics. These workshops included extensive lectures and hands-on guided tutorials. Included were detailed workbooks with many exercises and literature references as well as scripts for running complex modeling projects. These workbooks are available for anyone at UofL to work through.


application_id: 7381766
project_number: 5P20RR016481-06
project_title: BRIN:KENTUCKY BRIN MENTORING & TRAINING CORE
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-03-108
application_type: 5
activity_code: P20
ic: RR
serial_number: 016481
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-7(01)
subproject_number: 7160
contact_pi_person_id: 2101814
contact_pi: RAWLS, JOHN M
other_pis: Not Applicable
congressional_district: 03
department: ANATOMY/CELL BIOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. This is a ten-week residential program in which undergraduate students participate in genetic/genomics research projects under supervision of faculty and in cooperation with graduate students postdoctoral associates and other lab personnel. Our program focuses on rising sophomores and juniors of PUI institutions for whom this is an initial research activity. Students work cooperatively in groups of 2 or 3 primarily in executing genetic screens for novel mutations of genes that are under study in the sponsoring laboratories. The students personally carry out the screens to obtain the new mutations perform preliminary genetic analysis and perform initial molecular analysis of the mutations (e.g. PCR and DNA sequence analysis). During each week of the summer students meet and participate in colloquia of the entire group in which visiting scientists describe their work graduate program directors describe graduate training opportunities visits are made to campus facilities supporting genomics research and the students themselves present their work to the larger group. The capstone experience is presentation by each group of their research at the annual meeting of the Kentucky Academy of Sciences.   The students group for the summer of 2006 will be selected in March from applications that are currently being accumulated. A state-wide faculty committee chaired by Dr. Dawn Anderson (Berea College) distributes announcements to departments and faculty of PUIs solicits and screens applications and selected the pool of participants for both the UK and UL site programs. The faculty coordinators at UK (Rawls) and UL (Feldhoff) determine equitable parcelling of the pool to the two programs based upon interests and expressed preferences of the applicants and to assure equity of distribution of students from the various PUIs.  In the summer of 2005 (including the 7/1/05-8/7/05 portion of this reporting period twelve students participated in the UK program representing six undergraduate institutions (Bellarmine University Berea College Kentucky State University Pikeville College Transylvania University Western Kentucky University). They worked in groups with four faculty members (Harrison Lund Mirabito Rawls) on projects isolating and characterizing mutations of the model organisms Aspergillus Caenorhabditis and Drosophila.


application_id: 7381765
project_number: 5P20RR016481-06
project_title: BRIN: UL: KENTUCKY BRIN ADMINISTRATIVE CORE
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-03-108
application_type: 5
activity_code: P20
ic: RR
serial_number: 016481
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-7(01)
subproject_number: 7159
contact_pi_person_id: 1866398
contact_pi: COOPER, NIGEL G
other_pis: Not Applicable
congressional_district: 03
department: ANATOMY/CELL BIOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. This core does the following: 1) Manage budgets 2) Disemate information on policies & procedures 3) Collect & maintain records for annual report 4) Attend BRIN regional & national meetings 5) Development of database 6) Support & logistics for Steering Committee External Advisory Committee & Administrative Advisory Board 7) KBRIN Summer Undergraduate Program & faculty fellows 8) Bioinformatics Summit April 2006  9) Advertising & PR materials including a new newsletter 10)Coordinates Animal Care Oversight 11) Grant management support 12) Update & maintenance of the official KBRIN website 13) Support for program evaluation 14) Neuroscience & Bioinformatic Seminar Series 15) Provide support for genomics bioinformatics & Education & mentoring cores


application_id: 7381200
project_number: 5P20RR015592-07
project_title: HORMONE REGULATION OF CARDIAC INJURY
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-04-008
application_type: 5
activity_code: P20
ic: RR
serial_number: 015592
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-8(02)
subproject_number: 6595
contact_pi_person_id: 1896984
contact_pi: SMART, ERIC J
other_pis: Not Applicable
congressional_district: 06
department: OBSTETRICS & GYNECOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The central hypothesis of this proposal is that HDL-associated sex hormones (estrogen and testosterone) regulate the activity of cardiac myocyte constitutive nitric oxide synthase which subsequently affects the extent of ischemic injury.  Epidemiological studies demonstrate that women are less prone to ischemic heart disease than men. The mechanisms responsible the differences in ischemic injury observed between men and women are not know although the current focus is on sex hormones in particular estrogen and testosterone. A large number of studies have implicated estrogen-induced stimulation of constitutive nitric oxide synthase (cNOS) as providing protection against ischemic injury of cardiac myocytes. The role of testosterone is unclear with reports of protection against ischemic injury and reports of testosterone promoting ischemic injury. The majority of the studies on estrogen and testosterone do not distinguish between effects mediated by the endothelium in hearts and cardiac myocytes. One of the novel aspects of the proposed studies is that the preliminary data indicate that estrogen and testosterone have direct effects on cardiac myocytes independent of the endothelium. Another novel aspect of the proposed studies is that it is estrogen or testosterone associated with HDL that is responsible for the generation of nitric oxide in cardiac myocytes and protection/promotion of ischemic injury. The molecular mechanism whereby estrogen limits ischemic injury and testosterone increases ischemic injury will be tested in two Aims.  Aim 1: To determine the mechanism whereby HDL-associated estrogen stimulates the production of nitric oxide and limits ischemic injury. The preliminary studies suggest that estrogen receptor alpha and caveolin-1 form a complex that stimulates cNOS via AMP kinase. Cardiac myocytes isolated from wild type mice caveolin-1 null mice or estrogen receptor alpha null mice will be used along with dominant negative adenoviral constructs agonist/antagonists and enzyme assays to dissect the mechanism(s). In addition wild type mice SR-BI null mice caveolin-1 null mice and estrogen receptor alpha null mice along with ovariectomies and ovariectomies/estrogen replacement will be used to determine the effect on ischemic injury.   Aim 2: To determine the mechanism whereby HDL-associated testosterone decreases the generation of nitric oxide and increases ischemic injury. The preliminary studies demonstrate that HDL-associated testosterone decreases the generation of nitric oxide without affecting the cellular levels of cNOS. Isolated cardiac myocytes will be used to examine several possible mechanisms for the HDL-testosterone mediated inhibition of cNOS such as altered caveolin binding to cNOS depletion of caveolae cholesterol re-localization of cNOS and modification of cNOS and/or caveolin-1. Additional studies will determine if the androgen receptor and/or testosterone uptake are involved in this process. Wild type mice SR-BI null mice and caveolin-1 null mice along with orchidectomies and orchidectomies/testosterone replacement will be used to determine the effect on ischemic injury.


application_id: 7381199
project_number: 5P20RR015592-07
project_title: KY COBRE: PILOT PROJECTS
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-04-008
application_type: 5
activity_code: P20
ic: RR
serial_number: 015592
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-8(02)
subproject_number: 6594
contact_pi_person_id: 1896366
contact_pi: CURRY, THOMAS E
other_pis: Not Applicable
congressional_district: 06
department: OBSTETRICS & GYNECOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The COBRE in Women's Health funds new pilot projects in promising areas of research that complement the goals of the COBRE program to increase the critical mass of investigators with expertise and experience in women's health research


application_id: 7381198
project_number: 5P20RR015592-07
project_title: HORMONE ACTIONS ON BEHAVIOR: CLINICAL NEUROPHARMACOLOGY
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-04-008
application_type: 5
activity_code: P20
ic: RR
serial_number: 015592
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-8(02)
subproject_number: 6593
contact_pi_person_id: 1858700
contact_pi: KELLY, THOMAS J., MD, PHD
other_pis: Not Applicable
congressional_district: 06
department: OBSTETRICS & GYNECOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. Gonadal neurosteroids are important modulators of behavior and have been shown to impact a range of clinically significant conditions including sexual behavior sleep cognition drug and alcohol abuse affective disorders pain sensitivity epileptic seizure disorders and stress reactivity. Recent molecular and cellular studies as well as data from whole animal behavioral models indicate that gonadal neurosteroids influence behavior through the direct regulation of neuronal activity as well as the modulation of classical neurotransmitter function through a variety of both genonic and nongenomic mechanisms. To date the effects of estrogen and progesterone on neurotransmitter function in humans have received almost no attention. We and others have successfully used drug discrimination and functional neuroimaging methodologies to examine the manner in which psychoactive drugs alter classical neurotransmitter function (i.e. clinical neuropharmacological effects of drugs) as well as the neuroanatomical locations of these effects. This basic science project will be among the first to apply these methodologies within the same individuals to examine the manner and anatomical locations in which estrogen and progesterone modulate clinical neurotransmitter function in humans. One series of studies will examine the effects of estradiol on dopaminergic activity. It is hypothesized that estradiol will enhance dopamine function selectively in women. A second series of studies will examine the neuropharmacological effects of progesterone. It is hypothesized that progesterone and its metabolites will engender direct interoceptive effects via modulation of multiple receptor sites including GABA alpha and NMDA in both men and women. This information will be invaluable for expanding our understanding of the neurobiological basis of gender differences in mood and behavior regulation. These studies will have important applied significance in helping future development of gender-specific medications having selective effects at steroidal receptor sites and/or tailored to work in combination with endogenous neurosteroids. It is also likely that these studies will inform and enhance ongoing efforts to develop and evaluate steroid-based medications. Finally this project will promote the mentoring development and promotion of our junior and early career colleagues' academic interests in the clinical neurobiology of women's health.


application_id: 7381197
project_number: 5P20RR015592-07
project_title: ESTRADIOL INTERACTIONS WITH THE PROTEASOME IN HIV REGULATION
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-04-008
application_type: 5
activity_code: P20
ic: RR
serial_number: 015592
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-8(02)
subproject_number: 6592
contact_pi_person_id: 2306174
contact_pi: BRUCE-KELLER, ANNADORA J
other_pis: Not Applicable
congressional_district: 06
department: OBSTETRICS & GYNECOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The overall goal of this proposal is to test the hypothesis that estrogen can decrease HIV viral load by decreasing viral replication. As AIDS is now the third leading cause of death among women ages 25-44 understanding the role that female sex hormones might play in the physiology of HIV-1 infection is especially critical. Many manifestations of HIV differ in women including that women generally have lower HIV viral loads compared to men at similar stages of disease and have attenuated or absent disease progression during pregnancy. Conversely while studies suggest that women may be more vulnerable to certain AIDS-related illnesses such as HIV dementia and lipodystrophy there is data strongly suggesting that an estrogen deficient state can be associated with HIV infection. Evaluated as a whole this clinical evidence indicates that female hormones such as estrogen could act to maintain low viral titers and suggest that maintenance of serum estradiol levels could decrease the incidence of AIDS-related syndromes. While the mechanisms whereby estrogen modulates HIV infection are still very poorly understood data from our labs show that estrogen attenuates Tat-induceed transcription at the long-term repeat (LTR) domain of the HIV-1 promoter. These studies are thus designed to use novel molecular pharmacological and proteomic tools to determine the mechanisms whereby estrogen modulates HIV replication with specific emphasis on the role of the multicatalytic proteasome as a convergence point for estrogen and Tat in HIV regulation. The specific aims are to 1: To test the hypothesis that estrogen has specific negative effects on Tat-induced LTR activation; 2: To test the hypothesis that the effects of estrogen on the HIV-1 LTR are proteasome dependent; and 3: To determine the full proteomic mechanisms whereby estrogen modulates the HIV-1 LTR. Realization of these goals could lead to identification of novel and pertinent protein regulators of HIV-1 replication the manipulation of which might allow for more precise control over HIV infection in humans.


application_id: 7381196
project_number: 5P20RR015592-07
project_title: EFFECTS OF ESTRADIOL & ANTIDEPRESSANTS IN HIPPOCAMPAL NEUROGENESIS
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-04-008
application_type: 5
activity_code: P20
ic: RR
serial_number: 015592
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-8(02)
subproject_number: 6591
contact_pi_person_id: 1891759
contact_pi: JENNES, LOTHAR H
other_pis: Not Applicable
congressional_district: 06
department: OBSTETRICS & GYNECOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. Depressive disorders are a major health issue in the United States and cause severe social and economic problems. Currently most of these disorders are treated with Selective Serotonin Reuptake Inhibitors (SSRIs) which cause an increase in serotonin levels in the synaptic cleft. How this increased availability of serotonin causes beneficial effects is not clear however it appears that it stimulates the synthesis of Brain-Derived Neurotrophic Factor (BDNF) which in turn enhances neurogenesis in the dentate gyrus of the hippocampus. It is thought that the formation of new connectivities of these neurons is at least in part responsible for successful treatment of depression. Thus one goal is to identify the sites of actions as well as the mechanisms by which SSRIs cause an enhancement of BDNF levels in the hippocampus thereby stimulating neurogenesis. Many studies have shown that the frequency of depressive incidences increases in post-menopausal women and estrogen reduces depressive symptoms. Thus a second goal is to identify the estrogen-sensitive neurons that project to the hippocampus and are regulated by serotonin and to reveal the mechanisms by which estrogen reduces the frequency and severity of depressive episodes.  Aim 1: test the hypothesis that SSRIs and estrogen act on medial septal-diagonal band cholinergic neurons the prefrontal cortex as well as directly on the hippocampus to enhance BDNF synthesis and neurogenesis in an additive or synergistic fashion. Aim 2: test the hypothesis that medial septal-diagonal band cholinergic neurons and cortical GABAergic neurons are necessary for estradiol and SSRIs to stimulate BDNF synthesis and neurogenesis in the hippocampus. Aim 3: test the hypothesis that the transcript-specific BDNF promoters and the untranslated regions regulate the expression localization and function of BDNF.


application_id: 7381195
project_number: 5P20RR015592-07
project_title: HORMONE MEDIATED REGULATION OF OVARIAN FUNCTION
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-04-008
application_type: 5
activity_code: P20
ic: RR
serial_number: 015592
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-8(02)
subproject_number: 6590
contact_pi_person_id: 1896366
contact_pi: CURRY, THOMAS E
other_pis: Not Applicable
congressional_district: 06
department: OBSTETRICS & GYNECOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. This project explores estrogen action on the ovary and the mammary gland. Studies conducted during the past funding period have explored the changes in 1) the ovarian matrix metalloproteinases 2) ovarian gene expression and 3) a class of nuclear hormone receptors the peroxisome proliferator-activated receptors (PPARs) in mammary gland function. All four of the investigators associated with this project have made significant progress towards their individual experiments as well as towards establishing preliminary data for the competitive renewal of this Project. Dr. Misung Jo is continuing to examine the functional significance of a novel gene Runx1 in late follicle development. The localization pattern of Runx1 expression and the mechanism(s) of Runx1 expression continue to shed light on the functional role this protein plays in follicular development and ovulation. Preliminary experiments with silencing RNA have suggested that Runx1 may mediate the LH induced increase in progesterone production. Experiments by Dr. Michael Kilgore have continued to investigate the signal crosstalk between the estrogen receptor beta (ERb) and the peroxisome proliferator-activated receptor gamma (PPARg). Preliminary data indicates that crosstalk between these receptors results in gene-specific changes with a number of genes being upregulated while other genes are downregulated as seen by DNA microarray. Ongoing studies are examining the significance of these changes in gene expression on cellular proliferation and migration. Finally a series of breeding experiments by Dr. Jay Ko have been in progress to generate tissue-specific knockouts of the estrogen receptor (ER) isoforms. These ongoing studies are creating mice which lack ERa or ERb in the oocyte the granulosa cell or the theca cells. To date oocyte-specific estrogen receptor knockout have been generated which lack ERa. These mice exhibit a reduced ovulatory capacity although they are fertile. The impact of estrogen action on the theca and granulosa cell layers of the follicle will be explored as these mice become available. In Dr. Curry's laboratory the role and timing of expression of the matrix metalloproteinase-19 and its inhibitors in ovarian development and ovulation continues to be unraveled. These studies demonstrate the importance of tissue remodeling in regulating ovarian function and fertility. Therefore all the projects have made significant progress in developing the necessary tools to address the goals of each project and are in an excellent position to provide convincing data for the competitive renewal of the COBRE project as well as compete for extramural support.


application_id: 7381194
project_number: 5P20RR015592-07
project_title: KY COBRE: ADMINISTRATIVE CORE
administering_ic: NCRR
award_notice_date: 2006-06-01
opportunity_number: RFA-RR-04-008
application_type: 5
activity_code: P20
ic: RR
serial_number: 015592
project_start_date: 2006-05-01
project_end_date: 2007-04-30
study_section: ZRR1-RI-8(02)
subproject_number: 6589
contact_pi_person_id: 1896366
contact_pi: CURRY, THOMAS E
other_pis: Not Applicable
congressional_district: 06
department: OBSTETRICS & GYNECOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The Administrative Core will facilitate the research and training of the COBRE-WH scholars by:  1. providing the organizational and administrative structure that insures optimal dissemination of information among COBRE-WH investigators  2. insuring that the junior faculty obtain state-of-the-art broad-based training in a mentoring and stimulating environment that enhances their prospects of successfully establishing independent NIH-funded research careers  3. supporting critical Cores to promote optimal sharing of techniques and approaches       The Administrative Core has and will continue to support shared-use Cores to insure COBRE-WH investigators utilize state-of-the-art methods. We have chosen to focus our funds and attention on the same four core facilities: (A) the Animal Core (B) the Imaging Core (C) the Molecular and Cellular Core and (D) the Biostatistics Consulting Core.  4. funding new pilot projects in promising areas of research that complement the goals of the COBREWH to increase the critical mass of investigators with expertise and experience in women?s health research and  5. working with the Associate Dean for Research of the College of Medicine the Senior Associate Vice President for Research and departmental Chairs to increase the pool of faculty involved in women's health research by hiring new faculty members.


application_id: 7381136
project_number: 5P20RR015576-07
project_title: ROLE OF ESTROGEN AND PROGESTERONE IN SCI PAIN
administering_ic: NCRR
award_notice_date: 2006-07-21
opportunity_number: RFA-RR-04-008
application_type: 5
activity_code: P20
ic: RR
serial_number: 015576
project_start_date: 2006-06-01
project_end_date: 2007-05-31
study_section: ZRR1-RI-8(02)
subproject_number: 6531
contact_pi_person_id: 6490947
contact_pi: HUBSCHER, CHARLES H
other_pis: Not Applicable
congressional_district: 03
department: NEUROSURGERY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. Chronic central pain develops in the majority of spinal cord injury (SCI) patients following complete and partial injuries including at level allodynia (pain to touch in dermatomes at and just above the level of injury). Using a recently developed electrophysiological rat model (in vivo) for investigating the effects of chronic SCI on responses in supraspinal neurons new data from our lab was obtained which indicates that the development of at level allodynia is dramatically reduced after SCI in female rats with normal hormonal cycles compared to males/ovariectomized females. This raises the possibility that progesterone and/or estrogen could play therapeutic roles for SCI-induced pain. We also have evidence supporting the hypothesis that at level allodynia if and when it develops may result from damage to descending pathways in the dorsolateral quadrant in combination with sparing of at least a portion of ascending tract(s) in the ventrolateral quadrant that transmit to higher centers the information from dermatomes just above the level of injury. Moreover preliminary data indicate that the allodynia when it develops may be exacerbated by circulating progesterone and/or estrogen which is clearly seen in the responsiveness of brainstem neurons. This exacerbation is consistent with findings for numerous conditions with cycle related changes in pain thresholds in humans. Thus the development and perpetuation of at level allodynia will be examined relative to experimental variations of hormonal status and variations in specific patterns of damage/sparing. The underlying mechanism may include changes in the responses of neurons in the thalamus (an important region involved in the processing of inputs that ultimately lead to pain) which will be compared to the concomitant behavioral signs that accompany these changes (i.e. allodynia). Thus a unique feature of this proposal is the multidisciplinary approach that is taken i.e. using electrophysiological behavioral and anatomical measures for each animal. The proposed research will examine the underlying mechanisms related to ovarian hormones that prevent the development and contribute to the perpetuation of this clinically-relevant at level allodynia. Therefore these studies will lead to a better understanding of the neural mechanisms underlying SCI pain and will identify ovarian hormones as targets that can readily be modulated to prevent and treat SCI-related pain. This is very important since current drug therapies and surgical interventions are inadequate.


application_id: 7381135
project_number: 5P20RR015576-07
project_title: HEAT SHOCK PROTEINS IN SPINAL CORD NEURAL SURVIVAL
administering_ic: NCRR
award_notice_date: 2006-07-21
opportunity_number: RFA-RR-04-008
application_type: 5
activity_code: P20
ic: RR
serial_number: 015576
project_start_date: 2006-06-01
project_end_date: 2007-05-31
study_section: ZRR1-RI-8(02)
subproject_number: 6530
contact_pi_person_id: 6155708
contact_pi: GOZAL, EVELYNE
other_pis: Not Applicable
congressional_district: 03
department: NEUROSURGERY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. Spinal cord injury (SCI) and subsequent secondary cell death partially involves an ischemic component. Oligodendrocytes and astrocytes survival is critical to maintain cellular interactions in the white matter and limit secondary injury damage. The purpose of this proposal is to study heat shock proteins (hsps) induction and interactions in hypoxia/ischemia-exposed oligodendrocytes and astrocytes and identify molecules and signaling pathways associated with higher tolerance to ischemia. Hsps induced by various stresses are involved in protein refolding and repair and have been implicated in cellular ischemic tolerance in brain and in spinal cord. We will test the hypothesis that after SCI induction of hsp expression modulates glial cell survival signaling pathways to preserve oligodendrocyte / astrocyte integrity and interactions with neurons. The specific aims of this proposal are: 1. To examine the expression profile of heat shock proteins induced in hypoxic/ischemic oligodendrocytes and astrocytes in culture and in contused spinal cord. 2. To determine the effect of hsp on oligodendrocytes and astrocytes survival to hypoxia/ ischemic injury and after SCI. 3. To determine the mechanism(s) of hsp-related cell protection and the role of hsp binding proteins in hypoxia/ ischemia survival pathways and in cell death after SCI. Using embryonic oligodendrocyte precursors (OPCs) differentiated to either oligodendrocytes or astrocytes and exposed to hypoxia/ischemia we will assess heat shock proteins expression in a cellular model and correlate the levels of hsp expression with cell survival. In addition we will characterize the profile of hsps induced by SCI in rodent spinal cord. The effect of hsp gene overexpression or silencing on oligodendrocytes/astrocytes survival to cellular hypoxia/ ischemia and on SCI-induced delayed injury will be determined as well as the effect of experimental hsp induction in the whole animal on secondary injury-induced damage after SCI. Finally we will use proteomic approaches to identify protein-protein interactions with hsps induced by hypoxia/ischemia in oligodendro- cytes and in astrocytes and in differentially damaged areas of the spinal cord after SCI. Thus we will characterize signaling pathways underlying cellular differential sensitivity to hypoxia/ischemia and identify potential intervention targets in SCI. These studies will identify novel therapeutic approaches to preserve oligodendroglial support in injured spinal cord inhibit apoptosis and reduce delayed white matter injury.


application_id: 7381134
project_number: 5P20RR015576-07
project_title: REMYLINATION AS A MECHANISM FOR SPINAL CORD REPAIR
administering_ic: NCRR
award_notice_date: 2006-07-21
opportunity_number: RFA-RR-04-008
application_type: 5
activity_code: P20
ic: RR
serial_number: 015576
project_start_date: 2006-06-01
project_end_date: 2007-05-31
study_section: ZRR1-RI-8(02)
subproject_number: 6529
contact_pi_person_id: 8141627
contact_pi: CAO, QILIN
other_pis: Not Applicable
congressional_district: 03
department: NEUROSURGERY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. Demyelination contributes to the dysfunction after the traumatical spinal cord injury (SCI) in both humans and experimental animals. We hypothesize that remyelination of demyelinated but otherwise intact axons will facilitate the functional recovery. Our preliminary data showed that the combination of oligodendrocyte precursor cells (OPCs) transplantation and administration of D15A a novel neurotrophin with both NT3 and BDNF activities77 partially restored electrophysiological and behavioral function after contusive SCI. However many transplanted OPCs remained undifferentiated. Preliminary data also showed up-regulation of Notch signaling after SCI and activation of Notch signaling inhibited oligodendrocyte differentiation of OPCs in vitro. We propose that combination of blocking inhibitory Notch signaling increasing the expression of oligodendrocyte differentiation growth factor D15A and delivery of growth factor(s) known to potentiate myelination will further promote remyelination from engrafted OPCs and leads to greater functional recovery. We will test these strategies in a novel clinically relevant model of rat contusive SCI whose injury severity can be adjusted to cause enough loss of myelin and/or axons to result in specific behavioral and electrophysiological deficits but also sufficient sparing of demyelinated axons to enable remyelination. Objective and sensitive electrophysiological and behavioral tests will be used to examine if the increased remyelination will enhance functional recovery in this contusive SCI model. Collectively these experiments will provide a foundation to identify myelin-based therapies for SCI. There are three specific aims. Aim 1: To test if the combination of blocking inhibitory Notch signaling and increasing the expression of D15A in transplanted OPCs will lead to enhanced remyelination and functional recovery after acute SCI. This will identify the mechanism through which engrafted OPCs differentiate into oligodendrocytes in the adult injured spinal cord. Aim 2: To test if increasing the expression of growth factors that potentiate oligodendrocyte maturation and myelination will further promote remyelination from the grafted D15A+Notch- OPCs and facilitate functional recovery after acute SCI. This will provide important insight into mechanisms controlling the maturation and remyelination by oligodendrocytes in the injured spinal cord. Aim 3: To test if the optimal combinatory strategies established in acute SCI promote remyelination and functional recovery in the chronically injured spinal cord. This will identify the strategy to promote functional remyelination in the chronically injured spinal cord.


application_id: 7381133
project_number: 5P20RR015576-07
project_title: GSK3B AS A TARGET FOR PRO-NEURONAL SURVIVAL IN CNS NEURONS
administering_ic: NCRR
award_notice_date: 2006-07-21
opportunity_number: RFA-RR-04-008
application_type: 5
activity_code: P20
ic: RR
serial_number: 015576
project_start_date: 2006-06-01
project_end_date: 2007-05-31
study_section: ZRR1-RI-8(02)
subproject_number: 6528
contact_pi_person_id: 7612305
contact_pi: HETMAN, MICHAL
other_pis: Not Applicable
congressional_district: 03
department: NEUROSURGERY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. Cell death that follows traumatic CNS injuries contributes to permanent neurological deficits in trauma survivors. In spinal cord injury (SCI) axonal damage may result in denervation-induced neuronal apoptosis in cerebrocortical neurons. Therefore prevention of SCI-induced neuronal death in the cortex may be required for the successful repair of the spinal cord damage. Glycogen Synthase Kinase 3b (GSK3b) is a protein kinase that is involved in neuronal apoptosis induced by trophic support withdrawal. This implicates GSK3b as a potential target for the neuroprotective interventions. In healthy neurons the high basal activity of GSK3b is limited by inhibition through Akt-mediated phosphorylation at the serine 9 residue (pSer9). In addition recently published studies with PI's contribution revealed that basal or BDNF-stimulated ERK1/2 signaling activity inhibited the pro-apoptotic action of GSK3b in the absence of serine 9 phosphorylation. This suggests a novel pro-survival mechanism that controls neuronal GSK3b. This is further supported by our preliminary data indicating that moderate stimulation of glutamate NMDA receptors inhibited GSK3b-mediated apoptosis in pSer9-independent and ERK1/2-dependent manner. Furthermore we found that GSK3b is directly phosphorylated by ERK1/2 in vitro at a site that is distinct from Ser9. Therefore in addition to Ser9 phosphorylation GSK3b may be regulated by other mechanisms. In addition the full control over GSK-mediated cell death may require both pSer9-dependent and independent pathways. Consequently we hypothesize that the anti-apoptotic mechanisms activated by neurotrophins or glutamate include ERK1/2-mediated inhibition of GSK3b. Furthermore we propose that this inhibition is by the direct phosphorylation at a residue different than Ser9. We plan to further address this possibility through the studies organized into following specific aims: (i) dissection of the molecular mechanism employed by ERK1/2 to inhibit GSK3b (ii) identification of functional consequences of pSer9-independent regulation of GSK3b by ERK1/2 and (iii) testing the generality of ERK1/2-mediated regulation of GSK3b activity. We propose to use primary cultures of rat cortical neurons as a main system to address these issues. We would also like to validate the key observation done in cultures by in vivo experimentation using rat pups. This research is aimed on identification of novel signaling mechanisms that support neuronal survival in the cerebral cortex. Therefore it may provide potential targets for neuroprotective therapies in SCI and neurodegenerative disorders.


application_id: 7381132
project_number: 5P20RR015576-07
project_title: COBRE: UL: PKC REGULATION OF REGENERATION ACROSS CSPG AFTER SCI
administering_ic: NCRR
award_notice_date: 2006-07-21
opportunity_number: RFA-RR-04-008
application_type: 5
activity_code: P20
ic: RR
serial_number: 015576
project_start_date: 2006-06-01
project_end_date: 2007-05-31
study_section: ZRR1-RI-8(02)
subproject_number: 6527
contact_pi_person_id: 7936903
contact_pi: SHIELDS, CHRISTOPHER B
other_pis: Not Applicable
congressional_district: 03
department: NEUROSURGERY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. Glial scar formation after spinal cord injury (SCI) is central in the failure of axonal regeneration. Chondroitin sulfate proteoglycan (CSPG) is a class of major inhibitory molecules that is upregulated after SCI. We hypothesize that CSPG triggers PKC activation which induces a downstream activation of a small GTPase Rho and Rho-associated kinase (ROK) in sensory axons following SCI. We found that: 1) chondroitinase ABC an enzyme that removes CSPG's glycosaminoglycan (GAG) side chains had limited beneficial effect on DRG axon regeneration 2) the Rho inhibitor bacterial exotoxin C3 transferase applied to the spinal cord was neurotoxic at high doses 3) PKC phosphorylation is required for RhoA activation and 4) inhibitation of conventional PKC isoforms resulted in neurite outgrowth in vitro and regeneration of DRG axons in vivo. Understanding interactions between PKC and Rho/ROK activation and how they affect neurite outgrowth in vitro and axonal regeneration in vivo are mechanistic issues related to CNS injury and regeneration. We will use contusion and laceration SCI models as well as KO transgenic mice to investigate effects of PKC and its downstream Rho/ROK inhibition on DRG axon regeneration. Aim 1 will characterize the effect of conventional PKC and Rho/ROK inhibition on DRG neurite outgrowth on a CSPG substrate using an in vitro cell culture system. Aim 2 will investigate neurite outgrowth of engrafted DRG neurons within a CSPG-enriched glial scar environment developed after a contusive SCI in mice. Aim 3 will explore axonal regeneration of engrafted DRGs towards a CSPG-enriched gradient developed after a dorsal spinal cord laceration injury in adult mice in vivo. Aim 4 will study sensory axon regeneration of host DRGs through and beyond a spinal cord dorsal laceration injury under various pharmacological treatments including the PKC and RhoA/ROK inhibitors. We hope that understanding regulation of PKC-Rho-ROK signaling pathway may provide new insights into axon regeneraton through a glial scar and provide new directions for SCI repair.


application_id: 7381131
project_number: 5P20RR015576-07
project_title: COBRE: UL: MICROSCOPY CORE: CORE E
administering_ic: NCRR
award_notice_date: 2006-07-21
opportunity_number: RFA-RR-04-008
application_type: 5
activity_code: P20
ic: RR
serial_number: 015576
project_start_date: 2006-06-01
project_end_date: 2007-05-31
study_section: ZRR1-RI-8(02)
subproject_number: 6526
contact_pi_person_id: 6492007
contact_pi: ROISEN, FRED JERROLD
other_pis: Not Applicable
congressional_district: 03
department: NEUROSURGERY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The purpose of CORE E: Microscopy is to provide all projects with the personnel facilities resources and supplies to perform confocal TEM and SEM microscopy The procedures that will be available include tissue processing for plastic sectioning plastic sectioning and staining and immunofluorescence staining. Assistance and the expertise will be available for developing specialized microscopy procedures.


application_id: 7381130
project_number: 5P20RR015576-07
project_title: COBRE: MECHANISMS OF PLASTICITY & REPAIR AFTER SCI D: BEHAV & ELECTROPHYS CORE
administering_ic: NCRR
award_notice_date: 2006-07-21
opportunity_number: RFA-RR-04-008
application_type: 5
activity_code: P20
ic: RR
serial_number: 015576
project_start_date: 2006-06-01
project_end_date: 2007-05-31
study_section: ZRR1-RI-8(02)
subproject_number: 6525
contact_pi_person_id: 1932676
contact_pi: MAGNUSON, DAVID SK
other_pis: Not Applicable
congressional_district: 03
department: NEUROSURGERY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The purpose of the Electrophysiology and Behavior CORE (CORE D) is to provide a battery of standard tests to assess the function of animals and their spinal cords after injury and treatment and to facilitate the development of more specialized tests that may be needed for the COBRE projects. The CORE will provide the following tests: 1. Transcranial magnetic motor evoked potentials (tcMMEPs) to assess action potential conduction in descending axons located in the ventrolateral funiculus in rats and mice. 2. Somatosensory evoked potentials (SSEPs) to assess ascending primary sensory pathways (rats only). 3. Magnetic interenlargement reflexes (MIERs) to assess conduction in ascending propriospinal axons located in the lateral white matter (rats only). 4. Open Field Locomotor Scale (BBB) to assess hindlimb function during overground locomotioin in rats and the Basso Mouse Scale (BMS) for mice. 5. A grid-walking test to assess sensorimotor function. 6. The Louisville Swimming Scale (LSS; rats only) to assess hindlimb function during swimming. 7. Hindlimb kinematics during overground locomotion and swimming for rats and mice using joint angle limb excursion and step cycle duration as primary measures. 8. The Hargreave's test to assess cutaneous hyperalgesia. 9. Electro von Frey hairs to assess mechano-hypersensitivity after injury. In addition the CORE will pursue the development of novel electrophysiological and behavioral assessment tools as needed by specific projects within the COBRE laboratires.


application_id: 7381129
project_number: 5P20RR015576-07
project_title: COBRE: UL: MECHANISMS OF PLASTICITY AND REPAIR AFTER SCI/ C: SURGICAL CORE
administering_ic: NCRR
award_notice_date: 2006-07-21
opportunity_number: RFA-RR-04-008
application_type: 5
activity_code: P20
ic: RR
serial_number: 015576
project_start_date: 2006-06-01
project_end_date: 2007-05-31
study_section: ZRR1-RI-8(02)
subproject_number: 6524
contact_pi_person_id: 1932676
contact_pi: MAGNUSON, DAVID SK
other_pis: Not Applicable
congressional_district: 03
department: NEUROSURGERY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The purpose of Core C will be to significantly reduce variability in all Projects of the proposal by providing the expertise personnel facilities equipment and supplies required to reproducibly perform their surgery and veterinary care procedures. The standardized surgery procedures will include producing contusion and laceration types of spinal cord cord injuries in adult rats and mice plus cell transplantation injection neuroanatomical tracing cranial electrode implantation euthanasia perfusion fixation and tissue dissection. The standardized daily veterinary care procedures are designed to significantly reduce morbidity and mortality. They will include treating wounds expressing bladders preventing urinary tract and other infections plus providing supplemental fluids and nutrition.


application_id: 7381128
project_number: 5P20RR015576-07
project_title: COBRE: CELL CULTURE AND MOLECULAR BIOLOGY: CORE B
administering_ic: NCRR
award_notice_date: 2006-07-21
opportunity_number: RFA-RR-04-008
application_type: 5
activity_code: P20
ic: RR
serial_number: 015576
project_start_date: 2006-06-01
project_end_date: 2007-05-31
study_section: ZRR1-RI-8(02)
subproject_number: 6523
contact_pi_person_id: 1895692
contact_pi: WHITTEMORE, SCOTT R
other_pis: Not Applicable
congressional_district: 03
department: NEUROSURGERY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. CORE B: Cell and Molecular Biology CORE    CORE B shall meet all of the cell culture molecular biology and fluorescence-activated cell sorting (FACS) needs of the COBRE PIs who are not routinely using these methods in their own laboratories.   CORE B can provide stem and/or lineage restricted precursor cells derived from embryonic cortex or spinal cord. These can be from fetuses that constitutively express endogenous labels such as green fluorescent protein (GFP) or human placental alkaline phosphatase (hPLP) or they can be exogenous labeled or induced to express transgenes as described below.   CORE B can provide retroviral adenoviral and lentiviral vectors that express whatever cDNA the Investigators' need. In addition we have regulatable retroviruses (TetON and TetOFF) that are responsive to doxycyline both in vitro and in vivo.   CORE B has developed lentiviruses that express siRNA cassettes that we can target any mRNA that the COBRE Investigators' want silenced.   CORE B has also developed RNAse protection assays that can be modified to all Investigators' needs.   CORE B can provide expertise in quantiative real time PCR to assess mRNA levels for any gene of interest.  All of these reagents have been characterized by the CORE prior to their dispersal to the COBRE PIs to ensure quality control.


application_id: 7381127
project_number: 5P20RR015576-07
project_title: COBRE: UL: MECHANISMS OF PLASTICITY AND REPAIR AFTER SCI: A ADMIN CORE
administering_ic: NCRR
award_notice_date: 2006-07-21
opportunity_number: RFA-RR-04-008
application_type: 5
activity_code: P20
ic: RR
serial_number: 015576
project_start_date: 2006-06-01
project_end_date: 2007-05-31
study_section: ZRR1-RI-8(02)
subproject_number: 6522
contact_pi_person_id: 1895692
contact_pi: WHITTEMORE, SCOTT R
other_pis: Not Applicable
congressional_district: 03
department: NEUROSURGERY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. Core A will be responsible for the overall administration of this COBRE. Core A will coordinate all meetings between Principal Investigators and the Internal (IAC) and External (EAC) Advisory Committees as well as weekly seminar series and Visiting Lecturer Series. Drs. Whittemore Hagg and Xu will serve as mentors for each of the Projects and each individual having primary or secondary oversight for 2-4 Projects. CORE A will provide fiscal oversight of all Projects and CORES and also provide expertise in statistical analysis and experimental design for all Projects.


application_id: 7379988
project_number: 5R36AG029669-02
project_title: Genetic Regulation of Hematopoietic Stem Cell Number
administering_ic: NIA
award_notice_date: 2008-03-21
opportunity_number: PAR-06-117
application_type: 5
activity_code: R36
ic: AG
serial_number: 029669
program_official: WILLIAMS, JOHN
project_start_date: 2007-04-01
project_end_date: 2009-03-31
study_section: Biological Aging Study Section[NIA-B]
contact_pi_person_id: 8567496
contact_pi: WATERSTRAT, AMANDA JO
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
DESCRIPTION (provided by applicant):  The blood forming hematopoietic system like many other tissues and body systems relies on a long-lived and relatively small population of adult stem cells to replace cells that are lost or damaged during the process of aging. Given the host of age-related changes that occur in the hematopoietic system (Chen Astle et al. 1999; Geiger True et al. 2001; Edwards Howe et al. 2002; Campisi 2003; Penninx Guralnik et al. 2003; Pinto Filippi et al. 2003; Linton and Dorshkind 2004; Balducci and Ershler 2005; Chen 2005; Kamminga Os et al. 2005; Yuan Astle et al. 2005) and the quantitative and qualitative changes now known to occur in mouse Hematopoietic Stem Cells (HSCs) with age (Geiger True et al. 2001; Pinto Filippi et al. 2003; Chen 2005; Kamminga Os et al. 2005) we hypothesize that the regulatory mechanisms controlling HSCs are altered during the aging process in a way that contributes to or even produces aging phenotypes. In order to elucidate the mechanisms of HSC regulation a forward genetic investigation was initiated using two genetically distinct inbred mouse strains C57BL/6 (B6) and DBA/2 (D2). These strains were selected on the basis of striking inter-strain differences in both organismal longevity and HSC properties. Measuring HSC number in a panel of Recombinant Inbred strains generated by crossing the B6 and D2 parental strains allowed us to perform linkage analysis for this complex quantitative trait of HSC number. The results of the linkage analysis pointed to several genomic regions termed Quantitative Trait Loci (QTL) on chromosomes 123518 and X linked to HSC number in either young or old animals (Geiger True et al. 2001). These QTL represent a genetic network regulating HSC number between B6 and D2 mice. The identification of the specific genes and regulatory mechanisms corresponding to each QTL is underway. The experiments described in this proposal are designed to reveal the identity of the underlying gene within the QTL that was identified on Chromosome 5 (Chr5) and uncover the mechanism through which this gene effects HSC number. Two congenic mouse strains in which genes from the Chr5 QTL region were exchanged from B6 onto a D2 genetic background and D2 onto B6 serve as the models for isolating and functionally defining the QTG. First the identity of the gene will be revealed by microarray-based gene expression studies in HSCs from congenic and parental strains. Second the mechanism of action for this gene will be revealed by quantitatively comparing 4 major aspects of HSC regulation: cell cycle status cell cycling rate self-renewal capacity and degree of cell death in HSCs from both B6 D2 and congenic strains as well as HSCs induced to overexpress the QTG. While Americans are enjoying a substantial increase in life expectancy none who live into old age escape the seemingly inevitable physical impairments that accompany aging.   
  
In order to meet the medical financial and social needs of the ever-growing population of older Americans we must understand the mechanisms that control the natural aging process. Identification of the genetic regulatory mechanisms that dictate hematopoietic stem cell properties will provide invaluable insight into the mechanisms responsible for age- associated changes in stem cells that we believe lead to the functional declines of aging.

project_terms:
Affect;Age;Aging;Aging-Related Process;American;Anemia;Animals;Apoptosis;Blood;Bone Marrow;Bromodeoxyuridine;Cell Count;Cell Cycle;Cell Cycle Regulation;Cell Cycle Stage;Cell Death;Cell Lineage;Cells;Chromosomes Human Pair 1;Chromosomes Human Pair 5;Complex;Congenic Strain;DNA;DNA Binding;Dyes;Exhibits;Gene Expression;Genes;Genes Regulator;Genetic;Genomics;Hematopoietic;Hematopoietic System;Hematopoietic stem cells;Immunologic Deficiency Syndromes;Impairment;Incidence;Investigation;Lead;Life;Life Expectancy;Link;Longevity;Malignant Neoplasms;Measures;Medical;Mice Congenic;Mice Inbred Strains;Microarray Analysis;Modeling;Mouse Strains;Mus;Necrosis;Numbers;Older Population;Pattern;Phenotype;Ploidies;Population;Process;Property;Protein Overexpression;Quantitative Trait Loci;Rate;Recombinant Inbred Strain;Regulation;Series;Staining method;Stains;Stem cells;Strikes Employee;System;T-Lymphocyte;Testing;Thymidine;Time;Transplantation;adult stem cell;age related;analog;base;body system;congenic;design;functional decline;genetic linkage analysis;immune function;insight;peripheral blood;research study;self-renewal;social;trait


application_id: 7379039
project_number: 5M01RR002602-22
project_title: BEHAVIORAL EFFECTS OF DRUGS 08
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5142
contact_pi_person_id: 1888410
contact_pi: RUSH, CRAIG R
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The primary hypothesis is that the aripiprazole-cocaine combinations will be well tolerated and no adverse effects will occur. Secondary hypotheses include: 1) intranasal cocaine will produce prototypical stimulant-like subjective effects (e.g. increased ratings Drug Liking); 2) aripiprazole will produce mild transient side effects observed with antipsychotics (e.g. sedation performance impairment); and 3) aripiprazole maintenance will attenuate the subjective effects of intranasal cocaine (i.e. shift the cocaine dose-response curve rightward).  Cocaine abuse and dependence continue to be significant public health concerns. Despite intensive efforts by numerous research teams an effective pharmacotherapy for cocaine dependence has yet to be identified. The purpose of the present line of research is to examine the efficacy of aripiprazole as a putative agonist pharmacotherapy for cocaine dependence. The present study will examine the safety and tolerability of cocaine-aripiprazole combinations in 12 volunteers with history of cocaine abuse or dependence. We predict that the cocaine-aripiprazole combinations will be safe and tolerable.


application_id: 7379038
project_number: 5M01RR002602-22
project_title: REDOX MODULATION OF MUSCLE FUNCTION IN MICROGRAVITY
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5141
contact_pi_person_id: 1869134
contact_pi: REID, MICHAEL B
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. NASA's Critical Path Roadmap identifies loss of skeletal muscle function as a key concern for long-term missions to the International Space Station the Moon and Mars. Gravitational unloading causes weakness of antigravity muscles due to loss of muscle mass (atrophy) and contractile dysfunction. In selected conditions especially extravehicular activity (EVA) crewmember performance can also be limited by muscle fatigue. Ground-based studies suggest that oxidative stress contributes to loss of muscle function in both conditions unloading and strenuous exercise and that antioxidant pretreatment can protect muscle function. This experimental model is the basis for our current project. Experiments will evaluate a pharmacologic agent that has the potential to oppose oxidative stress in skeletal muscle and protect against muscle fatigue in flight crews. The experimental approach is explicitly pragmatic designed to identify and develop countermeasures for human testing in the near-to-mid term. The efficacy of the compound tested in this project is supported by preliminary data from animal studies and human trials and is currently approved for systemic administration to humans.


application_id: 7379037
project_number: 5M01RR002602-22
project_title: LINKING DEPRESSION WITH INCREASED MORBIDITY AND MORTALITY IN PATIENTS W HF
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5140
contact_pi_person_id: 1906318
contact_pi: MOSER, DEBRA KAY
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The purpose of this study is to explore these two potential mechanisms for the known association between depression and increased morbidity and mortality in Heart Failure (HF). The specfic aim for this study is to determine whether both Sympathetic nervous system (SNS) arousal and nonadherence contribute to the association between depression and poorer HF outcomes. This aim will be tested in a prospective correlational study in which the mediating effects of both DND arousal and nonadherence on the association between depression and the HF patient outcomes will be tested. A total of 300 patients with a confirmed diagnosis of chronic HF from an ischemic etiology with impaired left ventricular systolic function will be followed. Results of this study will provided vital information about the mechanisms linking depression and poor outcomes that clinicians and researchers can use in the design of effective intervention


application_id: 7379036
project_number: 5M01RR002602-22
project_title: GESTATIONAL DIABETES MELLITUS: IMPACT ON ORAL HEALTH
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5139
contact_pi_person_id: 1880406
contact_pi: NOVAK, KAREN F.
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. General hypothesis is that women with GDM are at higher risk for developing more severe periodontal disease than women without GDM and that the combination of GDM and periodontal disease will be associated with an increased negative impact on maternal and fetal health. The following Specific Aims are designed to address this question. To Characterize the prevalence extent and severity of of periodonitis and associations between periodontits and adverse maternal and fetal outcomes in women who develop GDM compared to women who don't develop GDM. Aim 2 will characterize the subgingival microbial ecology in women with GDM and periodontal disease and determine if specific microbial characteristics are associated with adverse pregnancy and fetal outcomes. Aim 3 will determine if patients with GDM and periodontitis have elevated levels of circulating inflammatory mediators comaper to women with GDM and no periodonititis and the non-GDM controls.


application_id: 7379035
project_number: 5M01RR002602-22
project_title: JC VIRUS EXPRESSION IN THE OROPHARYNX AND HIV
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5138
contact_pi_person_id: 8534501
contact_pi: BERGER, JOSEPH R
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. This study is an exploratory analysis of the difference in the prevalence of the JC Virus in oropharyngeal secretions and blood of healthy individuals persons with Acquired Immune Deficiency Syndroms (AIDS) and pes with progressive multifocal leukoencephalopathy (PML). Saliva and throat washings as well as whole blood samples will be taken from each group. Saliva samples and throat washings will be analyzed for JCV using polymerase chain reaction (PCR). Whole blood samples will be collected and analyzed for JCV using PCR and for the presence of JCV in peripheral blood leukocytes (PBLs) using CD4 lymphocyte counts. These measures will be used to determine whether JCV is harbored in the oropharynx whether a correlation exists between JCV levels in the oropharynx and those in PBLs and to determine whether the level and strain of JCV shed from the oropharynx correlates with the degree of immunosuppression. It is predicted that JCV will be present in oropharyngeal fluids the frequency of detection of JCV will be increased in patients with AIDS-associated PML compared with healthy controls and HIV-seropositive patients without PML and that higher levels of the JC Virus will correlate with increased immunosuppression.


application_id: 7379034
project_number: 5M01RR002602-22
project_title: BIOBEHAVIORAL INTERVENTION IN HEART FAILURE
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5137
contact_pi_person_id: 1906318
contact_pi: MOSER, DEBRA KAY
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The purpose of this study is to find out if relaxation training can produce beneficial changes in the psychological and physical health status of patients with heart failure.


application_id: 7379033
project_number: 5M01RR002602-22
project_title: SELECT
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5136
contact_pi_person_id: 8168805
contact_pi: ROWLAND, RANDALL
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The primary objective is to assess the effect of selenium and vitamin E alone and in combination on the clinical incidence of prostate cancer. A secondary objective is to assess the effect of selenium and vitamin E alone and in combination on the incidence of other cancers including lung cancer colorectal cancer and all cancers combined. Another secondary objective is to assess the effect of selenium and vitamin E alone and in combination on the following measures: prostate cancer free survival lung cancer free survival colorectal cancer free survival cancer free survival overall survival and serious cardiovascular events.


application_id: 7379032
project_number: 5M01RR002602-22
project_title: WARCEF
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5135
contact_pi_person_id: 1859648
contact_pi: PETTIGREW, L. CREED
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The primary specfic aim of this randomized double-blind multi-center clinical trial is to determine whether warfarin (International Normalized Ratio [INR] 2.5-3.0 target INR 2.75) or aspirin (325 mg per day) is superior for preventing all-cause mortality and stroke combined in patients with ejection fraction (EF) great than or equal to 30% when balanced against any risk of intracerebral hemorrhage. The secondary aim is to answer the following questions: (1) Is warfarin or aspirin superior for reducing stroke alone? (2) Among women is warfarin or aspirin therapy superior for reducing all-cause mortality stroke and MI combined when balanced against any increased risk of intracerebral hemorrhage? (3) Among African-Americans is warfarin or aspirin therapy superior for reducing all-cause mortality stroke and MI combined when balanced against any increased risk of intracerebral hemorrhage? (4) Does any relative risk of benefit of warfarin or aspirin for stroke TIA or periheral embolism depend on ejection fraction? (5) Does any relative risk or benefit of warfarin or aspirin depend on the heart failure class (NYHA class)? (6) Does any relative risk or benefit of warfarin or aspirin depend on etiology of cardiac failure? (7) Do warfarin and aspirin differ in their effect on cognitive function? (8) Does warfarin have a larger risk reduction relative to aspirin in cardioembolic than other stroke subtyped? (9) Are cardioembolic infarcts more frequent in patients with non-ischemic than ischemic caridiac diseases? (10) Are cardioembolic infarcts more frequent in women than in men? (11) Is mean cerebral infarct volume greater in patients with EF less than or equal to 20% than in patients with EF greater than 20%? A tertiary aim is to combine our data with that of the Warfarin Antiplatelet Trial in Chronic Heart Failure (WATCH) to provide more statistical power to address the secondary aims 1 through 6.


application_id: 7379031
project_number: 5M01RR002602-22
project_title: ALCOHOL-INDUCED HEPATIC P450S IN HCV/HIV OXIDATIVE INJURY
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5134
contact_pi_person_id: 2096899
contact_pi: SHEDLOFSKY, STEVEN I
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The objective of this proposal is to investigate the hypothesis that increased activities of specific P450 isoforms induced by ethanol contribute to hepatic injury via an oxidative mechanism in HCV infected and HCV/HIV co-infected patients.


application_id: 7379030
project_number: 5M01RR002602-22
project_title: PREDICTORS OF HAART RESPONSIVENESS IN HIV DEMENTIA
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5133
contact_pi_person_id: 8534501
contact_pi: BERGER, JOSEPH R
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The specific aims of this proposal are 1) to determine the relationship of metabolic and microvascular indices measured by MR to neuropsychologic status and to biological markers of the different proposed mechanisms of CNS toxicity and 2) to correlate the clinical/neurologic response to HAART (therapy composed of multiple anti-HIV drugs) with the metabolic and microvascular responses in the CNS.


application_id: 7379029
project_number: 5M01RR002602-22
project_title: TRANSPORT GENE EXPRESSION AND DRUG ACCUMULATION IN MILK
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5132
contact_pi_person_id: 3149046
contact_pi: MCNAMARA, PATRICK J
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The goal of the protocol is to systematically evaluate the role of genes in the accumulation of drugs into human milk. By identifying which transporters are present in mammary epithelial cells we hope to establish not only the identity of transporters for nitrofurantoin and cimetidine but to focus future studies on those classes of drugs likely to accumulate into milk. Functional studies will substantiate the role of these expressed transporters in the specific accumulation of nitrofurantoin and cimetidine. The further development of a model cell system that mimics the human mammary epithelial cell barrier will significantly enhance our understanding of the mechanisms of drug transport into milk.


application_id: 7379028
project_number: 5M01RR002602-22
project_title: BIOCHEMICAL MORPHOLOGICAL AND TRACE ELEMENT STUDIES IN ALZHEIMER'S DISESAE
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5131
contact_pi_person_id: 1894359
contact_pi: MARKESBERY, WILLIAM R
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The objective of the Alzheimer's Disease Research Center Clinical Core is to provide clinical data study participants and the means of obtaining autopsy materials for research. It is designed to aid research on current central scientific questions in AD and related diseases. The clinical core does not address these questions directly but makes available a group of well-characterized subjects to enable substantive research on these important current questions. To do this the clinical core 1) follows a group of community-dwelling normal elderly individuals to autopsy 2) follows an existing group of individuals with dementia to autopsy 3) evaluates and diagnoses individuals with memory disorders and 4) adds to the registry of individuals who are potential participants in research studies.


application_id: 7379027
project_number: 5M01RR002602-22
project_title: MODAFINIL AND NICOTINE IN ADOLESCENTS: PHASE I TRIAL
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5130
contact_pi_person_id: 8535709
contact_pi: MARTIN, CATHERINE ANNE
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The primary goal of this Phase I study is to demonstrate the safety of the combination of modafinil and nicotine replacement in nicotine dependent adolescent smokers. It is hypothesized that combined modafinil and nicotine replacement will assist in management of symtoms of inattention and depressed mood along with other nicotine withdrawal symptoms in tobacco-deprived nicotine dependent adolescent smokers. The safety of modafinil and nicotine alone and in combination will be assessed using physiological subjective and behavioral outcome measures in nicotine-dependent adolescent smokers. In addition behavioral and subjective measures of inattention and depressed mood along with other measures of nicotine withdrawal will also be measured to conduct an initial test of the potential efficacy of these drugs alone and in combination on these symptoms which are associated with relapse during smoking cessation. Information from this study will inform future clinical studies by examining safety and behavioral effects of these drugs alone and in combination.


application_id: 7379026
project_number: 5M01RR002602-22
project_title: MEMANTINE
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5129
contact_pi_person_id: 1926903
contact_pi: SANDERS, SHEILA K
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The aims of this study are to evaluate the effectiveness and safety of oral memantine in two daily dosing groups: 20 mg daily and 10 mg daily compared with placebo in patients with chronic open-angle glaucoma who are at risk for progression of the disease.


application_id: 7379025
project_number: 5M01RR002602-22
project_title: RENAL BONE DISEASE
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5128
contact_pi_person_id: 7875292
contact_pi: MALLUCHE, HARTMUT H
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The objectives of the proposed research are 1) to investigate in dialysis patients the relationship between activities of bone cells bone turnover and mRNA expression of parathyroid hormone receptor vitamin D receptor interleukin 1 tumor necrosis factor alpha; 2) to prospectively evaluate the effect of dialysis treatment on these mRNA species and bone turnover; and 3) to assess the relationship between C-terminal PTH/serum intact PTH ratio 1-84PTH 7-84PTH 1-84PTH:7-84PTH ratio and C-PTH-related protein levels and bone turnover. The effects of lowering or increasing serum calcium on the 1-84:7-84 PTH ratio.


application_id: 7379024
project_number: 5M01RR002602-22
project_title: LEPTIN ANOREXIA AND WEIGHT LOSS IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5127
contact_pi_person_id: 8535399
contact_pi: GAETKE, LISA M
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The purpose of this study is to determine possible etiologies for decreased food intake and weight loss in inflammatory bowel disease patients.


application_id: 7379023
project_number: 5M01RR002602-22
project_title: INFLAMMATORY MEDIATOR LEVELS IN PATIENTS WITH ADVANCED PERIODONTAL DISEASE
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5126
contact_pi_person_id: 2045756
contact_pi: CUNNINGHAM, LARRY L
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. Periodontal disease and dental caries are ubiquitous in the population. Recent literature has linked oral inflammatory conditions to elevations in circulating inflammatory mediators. In addition inflammatory mediators such as C-reactive protein have been linked to cardiovascular disease and a reduction of CRP has been shown to decrease the risk of MI and Stroke. The investigators propose to evaluate the levels of three inflammatory mediators CRP IL-6 and fibrinogen in patients with periodontal disease and dental caries who are having all their teeth removed prior to denture construction. They plan to follow these patients for one year with periodic re-evaluations with venipuncture to establish whether or not there is a decrease in these inflammatory mediators after elimination of oral disease.


application_id: 7379022
project_number: 5M01RR002602-22
project_title: LICIT AND ILLICIT OPIOIDS: COMPARATIVE STUDIES IN HUMANS: STUDY 1
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5125
contact_pi_person_id: 1877426
contact_pi: WALSH, SHARON L.
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. Epidemiological studies report increasing non-medical use and diversion of prescription opioid analgesics. Oxycodone is marketed in an array of formulations and used for the treatment of acute and chronic pain. Oxycontin is a sustained-release formulation which is marketed in higher dosage formulations compared to immediate release products; both formulations have received substantial negative publicity due to reports of increased frequency of unintentional addiction fatal overdose and criminal diversion. Hydrocodone a related semi-synthetic opioid is the most widely prescribed opioid analgesic in the United States and the most frequently mentioned prescription opioid in emergency room admissions. Despite their widespread clinical use few studies have evaluated the abuse liability and clinical pharmacology of these commonly used opioids. This project will employ controlled laboratory procedures to evaluate and characterize the effects of oxycodone and hydrocodone in volunteers with histories of opioid abuse under an array of conditions. This study will use a randomized placebo-controlled double-blind within-subject design. Dose rising pilot evaluations will precede randomized testing for safety purposes. Experiment 1 will compare the effects of oral oxycodone and hydrocodone to those of hydromorphone a mu opioid agonist with known high abuse potential and placebo over a broad range of doses. Physiological subjective and behavioral measures will be collected to assess safety and abuse liability respectively and a battery of psychomotor and cognitive tasks will assess the impairing effects of these agents. This study will contribute substantial new knowledge about the relative abuse potential and safety of these widely available agents at therapeutic and supratherapeutic doses in a population of subjects who are likely to abuse them. Information relevant to the public health will include the relative potency and tolerability of these compounds and empirical information relevant to safety scheduling and marketing of these agent


application_id: 7379021
project_number: 5M01RR002602-22
project_title: ECTOPIC LIPIDS IN CHROHN'S DISEASE
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5124
contact_pi_person_id: 3087686
contact_pi: LUU, LAN C
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The auto-immune and immune medicated pathologies of Crohn's Disease (CD) highlight the similarities it shares with Acquired Immunodeficiency Syndrome (AIDS) from the human immunodeficiency virus (HIV) specifically in the areas of pathophysiologies anthropometric alterations and metabolic abnormalities. Aims: Utilize proton magnetic resonance spectroscopy imaging to measure and to compare the levels of IMCL and IHL in active CD states to iactive CD states and both to health controls. Link the levels of IMCL and IHL to levels of inflammatory factors adipokines and ROS in active and inactive CD states compared to healthy controls. Determine the relationship between the levels of IMCL and IHL to resting quotient and energt expenditure using indirect calorimetry (IC) and doubly labeled water; to body composition using dual energy x-ray absorptiometry (DXA); and fasting plasma glucose levels as determined by an oral glucose tolerance test (OGTT). Model a metabolic profile of IMCL IHL and energy metabolism in Crohn's subjects to estimate appropriate sample size requirements for larger scale studies.


application_id: 7379020
project_number: 5M01RR002602-22
project_title: BEHAVORIAL EFFECTS OF DRUGS 06 B
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5123
contact_pi_person_id: 1888410
contact_pi: RUSH, CRAIG R
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The primary hypothesis is that the atomoxetine-cocaine combinations will be well tolerated and no adverse effects will occur. Secondary hypotheses include: 1) intranasal cocaine will produce prototypical stimulant-like subjective effects (e.g. increased ratings Drug Liking); 2) the two cocaine dose-response curves determined under placebo-maintenance conditions will not differ; 3) atomoxetine will produce mild transient side effects observed with stimulants (e.g. increased heart rate and blood pressure decreased appetite); and 4) atomoxetine maintenance will dose dependently attenuate the subjective effects of intranasal cocaine (i.e. shift the cocaine dose-response curve rightward).  Cocaine abuse and dependence continue to be significant public health concerns. Despite intensive efforts by numerous research teams an effective pharmacotherapy for cocaine dependence has yet to be identified. The purpose of the present line of research is to examine the efficacy of atomoxetine as a putative agonist pharmacotherapy for cocaine dependence. The present study will examine the safety and tolerability of cocaine-atomoxetine combinations in 12 volunteers with history of cocaine abuse or dependence. We predict that the cocaine-atomoxetine combinations will be safe and tolerable.


application_id: 7379019
project_number: 5M01RR002602-22
project_title: A PHARMACOLOGICAL ANALYSIS OF THC IN HUMANS (01)
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5122
contact_pi_person_id: 8046705
contact_pi: LILE, JOSHUA ANTHONY
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. To establish oral THC as a discriminative stimulus and characterize its effects on behavior and cognition. It is hypothesized that THC will function as a discriminative stimulus and produce other effects typically seen following cannabis administration. To determine if the effects of oral THC in humans can also be attributed to indirect involvement of the opioid GABA and DA systems. It is hypothesized that the opioid agonist hydromorphone and GABA modulator triazolam will partially substitue for THC and will have similar effects to THC on most expermental measures. In contrast it is hypothesized that the indirect DA agonist methylphenidate will not share discriminative-stimulus effects with THC and will have opposite effects on most experimental measures.


application_id: 7379018
project_number: 5M01RR002602-22
project_title: DIFFERENCES IN OPIOID-INDUCED HYPERALGESIA AND ANALGESIA
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5121
contact_pi_person_id: 6878921
contact_pi: HOLTMAN, JOSEPH R
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. Determine if low dose (subanalgesic) morphine produces an enhancement of pain sensitivity (hyeralgesia) in male and female subjects. Determine if the magnitude of the hyperalgesia is related to gender.


application_id: 7379017
project_number: 5M01RR002602-22
project_title: ALZHEIMER'S DISEASE NEUROIMAGING INITIATIVE (ADNI)
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5120
contact_pi_person_id: 1958116
contact_pi: SMITH, CHARLES K
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The overall goals of the Alzheimer's Disease Neuroimaging Initative Clinical Protocol will be to recruit 800 subjects and carry out all clinical evaluations including: neuropsychological and clinical assessments imaging studies and collection of biomarker.


application_id: 7379016
project_number: 5M01RR002602-22
project_title: COMPARISON BETWEEN TWO DIFFERENT CLOPIDOGREL MAINTENANCE DOSES
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5119
contact_pi_person_id: 1878190
contact_pi: HOLT, JOHN A
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. Increasing the maintenance dose of clopidogrel following a percutaneous intervention will result in increased suppression of platelet aggregation. The main goal of this study is to test whether an increase of the maintenance dose of clopidogrel from 75 to 150 mg per day results in an additional suppresion of ADP-induced platelet aggregation.


application_id: 7379015
project_number: 5M01RR002602-22
project_title: MINERALOCORTICOID RECEPTOR ANTAGONISM IN PATIENTS WITH ACS
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5118
contact_pi_person_id: 8854692
contact_pi: BROWN, BRANDON S
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. We hypothesis that eplerenone improves endothelial function reduces inflammation and the prothrombotic milieu in patients with acute coronary syndromes (ACS). Aim 1: To determine the effects of mineralocorticoid receptor (MR) antagonism on various indices of oxidative stress in patients with ACS. Obtain levels of G6PD in red blood cells and monocytes; NADPH and glutathione. Aim 2: To assess the effects of MR blockade on platelet activation in ACS. Evaluate the effect on the following activeation-dependent platelet antigen P-selection (CD62) expression platelet monocyte aggregates and plasma soluble CD40 ligand levels. Aim 3: To evaluate the effects of MR antagonism on inflammation in ACS by measuring the following markers of vascular inflammation high sensitivity CRP (hs-CRP) pregnancy-associated plasma protein A (PAPP-A) monocyte-chemoattractant protein (MCP-1) interleukin (IL)-6 serum amyloid A (SAA) and myeloperoxidase (MPO).


application_id: 7379014
project_number: 5M01RR002602-22
project_title: NUTRITIONAL INTAKE AND PROINFLAMMATORY CYTOKINE ACTIVITY IN COMMUNITY DWELLING S
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5117
contact_pi_person_id: 1906096
contact_pi: LENNIE, TERRY A
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. Proinflammatory cytokines are elevated in people with chronic illness and in healthy older adults. Whether these cytokines have the same negative effect on nutrient intake in healthy adults as in chronic illness is unknown. The purpose of the proposed research is to examine the relationships between nutritional intake and proinflammatory cytokine activity in a group of healthy older adults. Forty community-dwelling adults aged 65 years or older and free of chronic illness will be recruited for the study. Nutritional intake will be assessed using four-day food diaries. Blood will be drawn and serum analyzed for TNF? soluble TNF receptors sTNFR1 and sTNFR2 IL-1ra IL-2 IL-4 IL-6 IL-8 IL-10 endotoxin albumin CRP uric acid and lipid panel. A 24-hour urine will be collected and analyzed for sodium and nitrogen. A descriptive examination of total number of nutrient deficiencies per person will be used to describe the nutritional intake of the group. The interaction among inflammatory markers and nutrtional intake will be determined by comparing calorie intake protein intake and number of nutritional deficiencies between two groups divided by a median split of serum cytokine levels. The effect of dietary fatty acid intake on proinflammatory cytokine activity will be determine by comparing proinflammatory cytokine levels between two groups divided by median intake of three fatty acids. This study will provide data for comparison with our heart failure patients with respect to the effects of fatty acids on cytokine activity and whether cytokines are invovled in both the decrease in food intake associated with normal aging and heart failure. This information will assist in developing appropriate interventions to improve and maintain nutritional intake of older adults according to their health status.


application_id: 7379013
project_number: 5M01RR002602-22
project_title: OVERWEIGHT CHILDREN WITH THE METABOLIC SYNDROME
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5116
contact_pi_person_id: 1874385
contact_pi: ANDERSON, JAMES MORLEY
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The primary objective is to compare changes in weight and metabolic-syndrome parameters in overweight or obese preadolescents or adolescents in response to a lifestyle intervention including two servings of ready-to-eat cereal compared to the lifestyle intervention without cereal consumption. Primary endpoint is mean changes from baseline in body weight (absolute and percentage) at 6 and 12 weeks in BMI Z-score from baseline to 12 weeks for RTE cereal and control groups. Secondary end points are: mean changes from baseline in body weight at each clinic visit; mean change from baseline in waist circumference at 6 and 12 weeks; mean change from baseline in body compesition (DEXA); mean changes from baseline in serum lipid levels at 6 and 12 weeks; Incidence of side-effects in both treatment groups.


application_id: 7379012
project_number: 5M01RR002602-22
project_title: CIRCADIAN RHYTHM OF THE BONE REGULATING FACTORSHEMODIALYSIS
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5115
contact_pi_person_id: 8543097
contact_pi: MAWAD, HANNA
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The main hypothesis is that the circadian rhythms of 'intact' PTH PTH-(1-84) PTH-(7-84) PTH(1-84)/PTH(7-84) ratio and markers of bone formation and resorption are blunted in patients with CKD-5. This blunting is more pronounced in African American than in Caucasian patients and in diabetic than in non diabetic patients. Vitamin D treatment affects the circadian rhythms of PTH and bone markers. Specfic aims are to optain data on the above mentioned ratio. Compare these circadian rhythms of African American vs. Caucasian with CKD-5. To compare these circadian rhythms of diabetic vs. non diabetic patients with CKD-5. To compare these circadian rhythms in patients with CKD-5 on and off vitamin D treatment.


application_id: 7379011
project_number: 5M01RR002602-22
project_title: PHASE III TRIAL OF MINOCYCLINE IN AMYOTROPHIC LATERAL SCLEROSIS
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5114
contact_pi_person_id: 1975664
contact_pi: KASARSKIS, EDWARD JOSEPH
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. A multicenter RCT of mincocycline vs placebo. This study is an effort of the North East ALS Consortium.


application_id: 7379010
project_number: 5M01RR002602-22
project_title: PROJECT 5: ORAL INFECTIONS: DIETARY REGULATION OF LOCAL AND SYSTEMIC
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5113
contact_pi_person_id: 8263389
contact_pi: DAWSON, DOLPH R.
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. Periodontal disease is a chronic inflammatory condition that may have a significant negative impact on systemic conditions such as diabetes and cardiovascular disease and may increase the incidence of preterm birth in pregnant women. Preliminary studies have suggested that controlling oral infection and inflammation may have beneficial systemic effects. Our previous studies have demonstrated that combining traditional non-surgical periodontal therapy with supplemental anti-inflammatory agents provides improved clinical treatment outcomes and at the same time demonstrates a significant impact on systemic markers of inflammation. Many well-recognized disorders are associated with excessive intake of dietary fat including obesity insulin resistance coronary heart disease and some forms of cancer. While intake of saturated trans and arachidonic fatty acids (M) has been linked to the development of chronic disease research shows n-3 [polyunsaturated fatty acids (PUFA)] fatty acids specifically fish oils (eg. cold-water fish such as salmon cod tuna or mackerel) or plant oils (eg. flax linseed) can contribute to the prevention and treatment of disease. N-3 fatty acids together with the n-6 fatty acids are important components of a healthful diet. Fish oils are comprised of the essential fatty acids eicosapentaenoic acid (EPA C20:5 n-3) and docosahexaenoic acid (DHA C22:6 n-3). Both EPA and DHA fall into the category of PUPAs. Dietary n-3 PUPA have been shown to modulate inflammatory responses via regulating lymphocyte proliferation cytokine production signal transduction and gene expression in humans and rodents. Dietary n-3 PUPA provides a benefit by reducing inflammation and improving antibacterial and autoimmune responses. The effect of dietary lipid intake on resistance to infection suggests that n-3 PUPA are both anti-inflammatory and immunomodulatory.  The capacity for human diets enriched in n-3 PUPA to alter systemic responses to chronic inflammation has previously been demonstrated. It is speculated that the use of n-3 PUPA as a readily available dietary supplement with anti-inflammatory properties could have an important impact on resolving oral infection and inflammation when combined with traditional non-surgical periodontal therapies. In addition it is hypothesized that a combination of periodontal therapy and n-3 PUPA administration will provide a synergistically beneficial effect on the local and systemic markers of infection and inflammation that have previously been associated with periodontal disease. This proposal explores the potential for the use of dietary n-3 PUPA in the management of oral and systemic inflammation and evaluates its clinical inflammatory and antibacterial impact.


application_id: 7379009
project_number: 5M01RR002602-22
project_title: MEAL-RELATED CHANGES IN GUT HORMONES IN LEAN AND OBESE CHILDREN
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5112
contact_pi_person_id: 8650215
contact_pi: LOMENICK, JEFFERSON P
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. Obesity has become a pandemic with more than 1 billion people affected worldwide. More than 30% of children in the United States are now overweight or obese which has led to an increase in the incidence of hypertension hyperlipidemia and type 2 diabetes in the pediatric population. In the last decade much has been learned about the neuroendocrine control of appetite and weight especially the signaling pathways between adipose tissue and the brain. More recently studies have shown that hormones secreted by the intestine such as ghrelin and peptide YY (PYY) have important roles in energy balance by providing signals to the hypothalamus about hunger and satiety. Most of these studies have been done in adults with only limited information available in children. Even less is known about the roles of other intestinal hormones in appetite regulation in children such as pancreatic polypeptide (PP) cholecytokinin (CCK) and glucagon-like peptide 1 (GLP-1). We therefore propose to evaluate these hormone levels in a group of lean and obese children in order to improve our understanding of how appetite and energy balance are regulated.


application_id: 7379008
project_number: 5M01RR002602-22
project_title: RECONCILING BIOPHSYICAL AND PSYCHOLOGICAL MODELS IN OLDER WOMEN
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5111
contact_pi_person_id: 9224624
contact_pi: EWEN, HEIDI HARRIMAN
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. This study aims to combine biological and psychosocial research perspectives in the longitudinal reseach design to : 1) investigate the anticipated experienced and interpreted stresses associated with residential relocation for older women; 2)determine the relationships between psychosocial and physiological manifestations of stress adaptation; and 3) develpment of a model combining biological and psychosocial research perspectives and methods in the investigation of residential relocation stress.


application_id: 7379007
project_number: 5M01RR002602-22
project_title: PREVALENCE OF PATENT FORAMEN OVAL IN PATIENTS WITH MIGRAINES
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5110
contact_pi_person_id: 8543096
contact_pi: GURLEY, JOHN
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The primary objective of this study is to determine the prevalence of patent foramen ovale (PFO) in patients with history of migraine headaches accompanied with neurological aura. Potential subjects will be recruited from headache clinics in the departments of Medicine and Neurology. Screening for migraine headache and neurological aura will be performed by a questionnaire. Those subjects with recurrent migraine headache syndrome and auras will be screened for PFO with transthoracic echocardiography and intravenous contrast.  This is a prospective screening study to determine the prevalence of PFO as determined by the transthoracic echocardiography in a population of patients with migraine headache and aura.


application_id: 7379006
project_number: 5M01RR002602-22
project_title: TRIALNET NATURAL HISTORY STUDY OF TYPE I DIABETES
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5109
contact_pi_person_id: 1945934
contact_pi: KAROUNOS, DENNIS G
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The overall objective of this study is to perform baseline and repeat assessments over time of the metabolic and immunologic status of individuals at risk for T1D in order to: Characterize their risk for developing T1D; Describe the pathogenetic evolution of T1D; and Increase the understanding of the pathogenetic factors involved in the development of T1D.


application_id: 7379005
project_number: 5M01RR002602-22
project_title: GENETIC LINKAGE STUDY IN PARKINSON'S DISEASE (GENEPD)
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5108
contact_pi_person_id: 9405862
contact_pi: SLEVIN, JOHN T.
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The goal of this study is to identify genes involved in the susceptibility to Parkinson's disease and to identify risk factors that may interact with these genes in the disease expression. To meet this goal we need to recruit at least two living siblings meeting diagnostic criteria for PD who are willing to participate in this study.


application_id: 7379004
project_number: 5M01RR002602-22
project_title: LEVOFLOXACIN PHARMACOKINETICS IN THE OBESE
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5107
contact_pi_person_id: 8855520
contact_pi: MOREHEAD, RICHARD
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The objectives of this study is to describe the pharmacokinetics of levofloxacin 750mg in ambulatory obese volunteers and in hospitalized obese patients. The pharmacokinetics of a 750mg intravenous does of levofloxacin administered to severly obese volunteers will not differ significantly from that of obese hospitalized medical patients. Determine the following pharmacokinetic parameters of levofloxacin in ovese individuals: Cmax Tmax area under the concentration-time curve (AUC) volume of distribution elimination rate serum half-life and urine clearance. Investigate the correlation between levofloxacin volume of distribution and actual adipose mass as determined by the whole body potassium counter in ambulatory volunteers.


application_id: 7379003
project_number: 5M01RR002602-22
project_title: BMI NUTRITION INFLAMMATION AND HEART FAILURE OUTCOMES "AGAF"
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5106
contact_pi_person_id: 1906096
contact_pi: LENNIE, TERRY A
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. Our research interests include determining the effects of sodium intake on heart failure (HF) outcomes and demonstrating the effectiveness of interventions to improve dietary adherence. We are using three and four-day food diaries to measure intake of sodium and other nutrients in our studies. Given the potential for intentional or unintentional underreporting of food intake a means of validating accuracy of food diaries is required to increase the validity of these studies. The ratio between 24-hour urinary excretion and dietary intake of sodium or nitrogen is commonly used to verify accuracy of food diet records. Urinary recovery of para-amino benzoic acid (PABA) administered during urine collection period is used verify completeness of 24-hour urine collection. Values for these parameters have been established in healthy adults but not in patients with heart failure who have altered sodium regulation and frequently suffer from renal insufficiency. Therefore the primary aim of this study is to determine the ratio of urine excretion to dietary intake of sodium and nitrogen and the percent urinary excretion of PABA that can be used to verify the accuracy of food diaries in patients with HF. The study will be conducted in General Clinical Research Center (GCRC). The available resources and controlled environment of the GCRC also provide an ideal opportunity for us to compare different methods of measuring body composition in this population and to determine whether short-term recordings of heart rate variability can be used to measure autonomic nervous system activity. The secondary aims of this study are (1) to compare one hour and five minute readings of heart rate variability to 24 hour measurements (2) to compare three methods of measuring body composition and (3) to increase our understanding of patient perceptions of living with HF and barriers to self-management. Twenty patients with HF of ischemic origin matched for gender and level of renal function will be admitted to the GCRC for one visit of approximately 56 hours arriving the night before the first study day. Patients will be provided a 2 gm sodium diet prepared by the dietician on the first day and will eat a diet of their choosing on the second day. They will take 80 mg of PABA with each meal on Day One. Separate 24-hour urines will be collected for each of the two study days. Food intake and urine collection will be closely monitored by trained research nurses. Additionally on Day One patients will wear a Holter monitor have an indwelling intravenous catheter inserted for drawing norepinephrine B-type natriuretic peptide and creatinine will perform a five minute structured breathing exercise and fill out a series of questionnaires. On Day Two they will have body composition measured by dual x-ray absorptiometry multi-frequency bioelectrical impedance spectroscopy and athropometrics. The data collected in this study will provide essential information to refine current and future research studies.


application_id: 7379002
project_number: 5M01RR002602-22
project_title: METABOLIC BONE DISEASES REGISTRY
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5105
contact_pi_person_id: 8543097
contact_pi: MAWAD, HANNA
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The main hypothesis is that by increasing the number of patients studied including every possible scenario i.e. underlying diseases therapeutic modalities race geography etc certain guidelines could be drafted for the management of these patients tailored to their specific conditions based on non-invasive parameters and thus minimizing the need for more invasive intervention i.e. bone biopsy.


application_id: 7379001
project_number: 5M01RR002602-22
project_title: ALZHEIMER'S DISEASE RESEARCH CENTER AD PATIENTS
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5104
contact_pi_person_id: 1958116
contact_pi: SMITH, CHARLES K
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The overall goal of the Clinical Core of The University of Kentucky Alzheimer's Disease Research Center (UK ADRC) is to support the research mission of the ADRC and provide excellent clinical diagnoses and care for patients with Alzheimer's disease (AD) and non-AD dementing disorders. It will: (1) maintain a normal control (BRAiNS clinic) of 500 initially normal aged subjects who will be followed longitudinally to autopsy. Emphasis will be on normal aging and transition to Mild Cognitive Impairment (MCI) and early AD; (2) maintain a Research Clinic of 200 subjects with probable AD and other non-AD dementias who will be followed longitudinally to autopsy; and (3) establish a group of 100 initially normal rural Appalachian aged subjects followed longitudinally to autopsy in the Berea Rural Appalachian Satellite Clinic for comparison to the urban based BRAiNS Clinic. The control participants are evaluated annually using neuropsychological tests to detect subtle changes in memory and other cognitive function designed to detect transition to MCI and dementia. Many existing and planned research projects at UK are dependent on autopsy specimens from normal subjects and those with MCI or early AD. The core holds important consensus diagnostic conferences and relates closely to the Neuropathology and Biostatistics and Data Management Cores. The Clinical Core will provide expert dementia diagnostic services in a referral Memory Disorders Evaluation Clinic for approximately 300 patients per year a group which serves as a recruiting pool for the Research Clinic and for clinical trials and other research studies. The core will expand and maintain a clinic for African Americans in Lexington the Kentucky Clinic North Minority Emphasis Clinic providing longitudinal care and broadening research opportunities to an understudied population. This core participates in the NIA LOAD genetic initiative NACC funded studies and ADCS trials. All appropriate data are collected and submitted to NACC in a timely manner.


application_id: 7379000
project_number: 5M01RR002602-22
project_title: TOBACCO AND ATTENTION: PHARMACOLOGICAL STUDY (TAPS)
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5103
contact_pi_person_id: 8535709
contact_pi: MARTIN, CATHERINE ANNE
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. This study compares the behavioral effects of methylphenidate amphetamine bupropion modafinil and guanficine on both nicotine withdrawal and nicotine effects in late adolescent and young adult smokers. The subject will receive only one medication per study. Comparison of methylphenidate amphetamine bupropion modafinil and guanficine effects on behavioral indices of abuse liability and therapeutic effects as well as on smoking topography and nicotine effects and nicotine withdrawal while smoking research tobacco cigarettes with and without nicotine will be completed in 12 (6 males and 6 females) nicotine dependent smokers per drug condition (methylphenidate amphetamine bupropion modafinil and guanficine) for a total of 60 subjects completing 7 sessions each. Placebo capsule and a denicotinized cigarette will be tested on the first session (data will not be analyzed) and one additional time which will be randomly assigned throughout the study so that neither participants nor study staff will be aware of the test condition on any given session. Twelve subjects will receive (1) two low doses of methylphenidate (or amphetamine; bupropion modafinil and guanficine) with one dose being administered with a nicotinized cigarette and the other with a denicotinized cigarette and (2) two high therapeutic doses of methylphenidate (or amphetamine; bupropion modafinil and guanficine) with one dose being administered with a nicotinized cigarette and the other with a denicotinzed cigarette. Low and high dose medication with nicotinized and denicotinized cigarettes will be administered for all 5 drug conditions: methylphenidate amphetamine bupropion modafinil and guanficine. Placebo and active doses will be administered in random order allowing for the measurement of changes in performance across the study. In each drug condition subjects are given the cigarette with and without nicotine after 24-hour forced abstinence. Drug effects will be assessed using a double-blind placebo-controlled crossover study using repeated measures over 4 hours. These studies will allow within and across subject comparisons.


application_id: 7378999
project_number: 5M01RR002602-22
project_title: EARLY TREATMENT OF ALS WITH NUTRITION AND NIPPV
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5102
contact_pi_person_id: 1975664
contact_pi: KASARSKIS, EDWARD JOSEPH
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. This is a multicenter Pilot Study to develop methods for a definitive Phase III trial. The specific aims of this Pilot Study are 1) To develop and validate strategies to improve tolerability of NIPPV to identify factors that influence acceptance of this treatment modality and to evaluate measures of early respiratory dysfunction; and 2) To develop and validate methods to determine energy balance in ALS.


application_id: 7378998
project_number: 5M01RR002602-22
project_title: SECONDARY PREVENTION OF SMALL SUBCORTICAL STROKES (SPS3)
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5101
contact_pi_person_id: 8543099
contact_pi: VAISHNAV, ANAND
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The overall aim of the Secondary Prevention of Small Subcortical Strokes (SPS3) project is to define efficacious therapies for cerebral small artery disease and its two most common clinical manifestations: small subcortical strokes (S3 also called lacunar strokes) and cognitive decline (vascular dementia). Optimal antiplatelet therapy and antihypertensive management of S3 patients to reduce stroke recurrence and cognitive decline has not been defined and is likely to yield important health benefits. Primary aims are to determine whether combination antiplatelet therapy consisting of aspirin plus clopidogrel is superior to aspirin for reducing recurrent stroke cognitive decline and major vascular events. Also to determine whether "intensive" blood pressure lowering to a specific target range is superior to "usual" hypertension management for reducing recurrent stroke cognitive decline and major vascular events.


application_id: 7378997
project_number: 5M01RR002602-22
project_title: AMIFOSTINE
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5100
contact_pi_person_id: 8543098
contact_pi: KUDRIMOTI, MAHESH
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The primary objective of this trial is to compare the incidence of grade 3/4 mucositis in patients receiving amifostine (Ethyol) while undergoing HYPERRADPLAT to that of the incidence of grade 3/4 mucositis previously reported in patients who received a single injection of IA cisplatin in UK studies.


application_id: 7378996
project_number: 5M01RR002602-22
project_title: BORTEZOMIB WITH WEEKLY IDARUBICIN FOR THE TREATMENT OF AML
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5099
contact_pi_person_id: 8535501
contact_pi: HOWARD, DIANNA S
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. To determine safety and efficacy of bortezomib (PS-341) in combination with idarubicin in a phase I and II clinical trial for patients with AML. The rationale for this novel clinical trial is based on our preclinical studies demonstrating a strong tumor-specific induction of apoptosis for primary human AML cells using the combination of bortezomib and idarubicin. Elderly and relapsed AML patients have been targeted for this study due to the lack of a "standard of care" and poor outcomes for these patients owing to a preponderance of poor-risk cytogenetics multi-drug resistance and antecedent co-morbidities. We expect to define dose-limiting toxicities and a maximal tolerated dose of bortezimib when combined with idarubicin in a phase I study; subsequently safety and efficacy of the combination at the designated dose will be explored in a phase II study with expanded enrollment. We anticipate that with this regimen we will observe potent anti-leukemia activity complete clinical remissions and less overall toxicity.


application_id: 7378995
project_number: 5M01RR002602-22
project_title: NUTRITIONAL ROLE IN PATIENTS RECOVERING FROM SEVERE ODONTOGENIC INFECTION
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5098
contact_pi_person_id: 2045756
contact_pi: CUNNINGHAM, LARRY L
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. Low levels of plasma protein such as albumin transferrin and retinal-binding proteins act as nutritional indicators during and following recovery of infection. Recent studies indicate that prealbumin can be used to measure hepatic function in correlation with recovery. Prealbumin also know as transthyretin is a 54 000 D protein synthesized primarily by the liver. Its main function is to transport thyroxine and indirectly viamin A. Because pre-albumin has a relatively short half-life of 1. 8 days compared to albumin (20 days) and transferrin (8 days) it may be used as a more timely reflection of protein levels. Protein malnutrion is linked to imparied host defense mechanisms most notable cell-mediated immunity. Early recognition of protein-energy malnutrition (PEM) is useful in preventing sepsis morbidity and morality. Prealbumin has been used as one of these indicators. There is also evidence that patients have a relative risk (RR) of deah between two-and tenfold or more depending on the severity of PEM and the interaction of PEM with other factors. These factors can include: age anemia socioeconomic factors or behavorial factors. Severity of PEM has been shown to lengthen healing time following infection decrease immunocompetence and increase post-operative complications.


application_id: 7378994
project_number: 5M01RR002602-22
project_title: CLOPIDOGREL WITH ASPIRIN AFTER OFF-PUMP CORONARY ARTERY BYPASS SURGERY
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5097
contact_pi_person_id: 6795654
contact_pi: AKERS, W S
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The purpose of this study is to determine the safety of clopidogrel in combination with aspirin during the immediate postoperative period following OPCAB surgery. We hypothesize that there will be no difference in chest tube drainage in patients who have undergone OPCAB surgery and randomized to aspirin or aspirin plus clopidogrel during the immediate postoperative period.


application_id: 7378993
project_number: 5M01RR002602-22
project_title: EXERCISE BELIEFS AND BEHAVIORS OF EARLY ADOLESCENTS
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5096
contact_pi_person_id: 7877347
contact_pi: GRIFFITH, JOAN R
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The aim of this study is to examine some of the psychosocial factors that are associated with the establishment and maintenance of physical activity throughout early adolescence.


application_id: 7378992
project_number: 5M01RR002602-22
project_title: ALZHEIMER'S DISEASE GENETICS INITIATIVE: THE MULTIPLEX FAMILY STUDY
administering_ic: NCRR
award_notice_date: 2006-04-17
application_type: 5
activity_code: M01
ic: RR
serial_number: 002602
project_start_date: 2006-04-01
project_end_date: 2007-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5095
contact_pi_person_id: 1958116
contact_pi: SMITH, CHARLES K
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2006-04-01
project_abstract:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source and thus could be represented in other CRISP entries. The institution listed is for the Center which is not necessarily the institution for the investigator. The purpose of the NIA Genetics Initiative: Multiplex Family Study is to identify families with multiple members diagnosed with late-onset Alzheimer's Disease. Families will be characterized clinically and blood samples will be collected to establish cell lines. If a blood sample is not available autopsy samples will be collected for DNA extraction and storage. Our goal is to recruit 1000 families in three years. Clinical and demographic data from these families will be collected at the local site and coded data without identifiers will be sent and included in a national database of families with Alzheimer's Disease. This database along with biological samples will be housed at the National Cell Repository for Alzheimer's Disease (NCRAD) at Indiana University. The biological samples and data from these families will be available to qualified researchers who must sign a Material Transfer Agreement before receiving DNA and data. An oversight committee knows as the Cell Bank Advisory Committee (CBAC) will review and monitor the process of family identification and enrollment data collection the establishment of cell lines and access to samples.


application_id: 7373835
project_number: 1R01DE018215-01A1
project_title: NUTRITIONAL EPIGENETICS AND OROFACIAL DEVELOPMENT
administering_ic: NIDCR
award_notice_date: 2008-08-01
opportunity_number: PA-07-070
application_type: 1
activity_code: R01
ic: DE
serial_number: 018215
suffix: A1
program_official: SCHOLNICK, STEVEN
project_start_date: 2008-08-01
project_end_date: 2012-07-31
study_section: Skeletal Biology Development and Disease Study Section[SBDD]
contact_pi_person_id: 1861667
contact_pi: GREENE, ROBERT M
other_pis: Not Applicable
congressional_district: 03
department: DENTISTRY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF DENTISTRY/ORAL HYGN
organization_zip: 402920001
organization_country: UNITED STATES
project_terms:
Address;Apoptosis;Branchial arch structure;Candidate Disease Gene;Cells;Child;Cleaved cell;Complex;Condition;CpG Islands;DNA Methylation;Defect;Development;Diet;Embryo;Epigenetic Process;Exhibits;Face;Family;Folate;Folic Acid Deficiency;Frequencies (time pattern);Gene Expression;Growth;Growth Fetal;Healthcare;Island;Live Birth;Mammalian Cell;Methylation;Modification;Molecular Target;Morphogenesis;Mus;Normal tissue morphology;Nutritional;Pattern;Phenotype;Promotor (Genetics);Protocols Treatment;Signal Transduction;Supplementation;Tissues;Vitamin B Complex;Water;Woman;Women's Health;craniofacial;malformation;novel;orofacial;prenatal


application_id: 7373784
project_number: 1R01EY017131-01A2
project_title: Proteomic Analysis of Retinal Ganglion Cell Death in Glaucoma
administering_ic: NEI
award_notice_date: 2007-11-19
opportunity_number: PA-07-070
application_type: 1
activity_code: R01
ic: EY
serial_number: 017131
suffix: A2
program_official: AGARWAL, NEERAJ
project_start_date: 2007-12-01
project_end_date: 2010-11-30
study_section: Anterior Eye Disease Study Section[AED]
contact_pi_person_id: 6803489
contact_pi: TEZEL, GULGUN
other_pis: Not Applicable
congressional_district: 03
department: OPHTHALMOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
project_abstract:
DESCRIPTION (provided by applicant): Only through a better understanding of the pathogenic mechanisms of glaucoma will improved and innovative treatments evolve. Preliminary studies using different series of in vitro and in vivo experiments as well as histopathological studies using human donor eyes have provided evidence that alterations in protein expression protein protein interactions post translational protein modifications and proteolytic cleavage change the protein complement of retinal ganglion cells (RGCs) during glaucomatous neurodegeneration with important implications in pathogenic mechanisms. The proposed experiments in this application are based on the hypothesis that an innovative analytical approach using the proteomics technology can identify time dependent alterations in the RGC protein complement on a large scale which characterize precise mechanisms of the RGC response to injury from initial insult to execution of cell death in glaucoma. The specific aims that will address this hypothesis include the identification of alterations in the RGC protein expression and post translational protein modifications during the course of glaucomatous neurodegeneration in an experimental rat model of chronic pressure induced glaucoma. Time dependent alterations of the RGC proteome such as up regulation or down regulation of protein expression will be quantitatively evaluated by comparing the proteomic datasets between ocular hypertensive and control eyes using RGC protein samples obtained at different time points by pooling from rat eyes matched for intraocular pressure (IOP) exposure and axon loss. Relationship between the differential protein expression and the level of IOP exposure and axon loss will be statistically determined. To improve the sensitivity of the detection identification and relative quantification of protein expression complementary proteomic approaches will be utilized which will include 2D PAGE based and gel free techniques using mass spectrometry. Oxidatively modified RGC proteins will be identified through 2D oxylot analysis and phosphorylated RGC proteins and their interacting proteins in enriched phosphoprotein complexes will be identified through complementary approaches of the targeted proteomics. Parallel experiments will also determine cellular localization of the identified proteins using immunohistochemistry. In addition to histological sections obtained from ocular hypertensive and control rat eyes glaucomatous and normal retinas obtained from human donor eyes will also be utilized to better validate the relevance of new findings to human disease. These studies should provide comprehensive information about the cellular mechanisms associated with RGC death at the protein level thereby offering biomarkers and novel treatment targets for neuroprotective interventions in glaucoma a leading cause of blindness. The information obtained from these studies is also expected to be useful in multiple disciplines to characterize pathogenic processes of various other neurodegenerative diseases leading to RGC death.   
In glaucoma a specific type of nerve cells the retinal ganglion cells progressively die leading to gradual loss of visual function. Since the current treatment of this blinding disease is not sufficient to prevent disease progression additional treatment strategies need to be developed to protect these cells in glaucomatous eyes. As a requirement to accomplish this goal this project aims to identify the precise mechanisms associated with the nerve cell death in glaucoma using a powerful technology in animal experiments as well as performing experiments utilizing human donor eyes. These studies are expected to provide comprehensive information about the nerve cell death process thereby allowing new treatment possibilities for 3 million Americans suffering from glaucoma.

project_terms:
Address;American;Axon;Biological Markers;Blindness;Cell Death;Cell Death Process;Cells;Chronic;Complement;Complex;Data Set;Detection;Discipline;Disease;Disease Progression;Down-Regulation;Experiments Animal;Eye;Gel;Glaucoma;Goals;Human;Immunohistochemistry;In Vitro;Intervention;Modeling;Nerve Degeneration;Neurodegenerative Disorders;Neurons;Ocular Hypertension;Phosphoproteins;Physiologic Intraocular Pressure;Polyacrylamide Gel Electrophoresis Two-Dimensional;Pressure- physical agent;Process;Protein Processing Post-Translational;Proteins;Proteome;Proteomics;Rattus;Relative (related person);Retina;Retinal Ganglion Cells;Sampling;Series;Spectrum Analysis Mass;Techniques;Technology;Time;Transcriptional Activation;Up-Regulation (Physiology);Vision;base;human disease;improved;in vivo;innovation;novel;prevent;protein expression;protein protein interaction;research study;response to injury


application_id: 7373749
project_number: 2R01DK055664-06A2
project_title: Hepatocyte Nitric Oxide Synthase Regulation by Glucagon and Insulin
administering_ic: NIDDK
award_notice_date: 2007-09-28
opportunity_number: PA-07-070
application_type: 2
activity_code: R01
ic: DK
serial_number: 055664
suffix: A2
program_official: SERRANO, JOSE
project_start_date: 2001-02-15
project_end_date: 2012-11-30
study_section: Surgery, Anesthesiology and Trauma Study Section[SAT]
contact_pi_person_id: 2093531
contact_pi: HARBRECHT, BRIAN G.
other_pis: Not Applicable
congressional_district: 03
department: SURGERY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
project_terms:
Adult;Area;Biology;Blood Glucose;Calcium;Caring;Cell physiology;Cessation of life;Complex;Critical Care;Critical Illness;Cyclic AMP;Cyclic AMP-Dependent Protein Kinases;Data;Development;Endocrinology;Event;Functional disorder;Glucagon;Guanine Nucleotide Exchange Factors;Hepatic;Hepatocyte;Hormones;Immune;Immune response;In Vitro;Infection;Inflammation;Injury;Insulin;Intracellular Second Messenger;Lead;Mediating;Mediator of activation protein;Metabolism;Molecular;Mortality Vital Statistics;Multiple Organ Failure;NOS2A protein human;Nitric Oxide;Nuclear;Operative Surgical Procedures;Organ;Pathway interactions;Patients;Physiological;Production;Regulation;Research;Role;Science of nutrition;Second Messenger Systems;Sepsis;Septic Shock;Series;Shock;Signal Pathway;Signal Transduction;Stimulus;Study Section;Tissues;Transplantation;Work;base;cytokine;improved;in vivo;novel;prevent;programs;response;septic


application_id: 7373470
project_number: 1R01HL088389-01A1
project_title: A Novel Mechanism by which iPLA2 Links Diabetes to Cardiovascular Diseases
administering_ic: NHLBI
award_notice_date: 2008-03-05
opportunity_number: PA-07-070
application_type: 1
activity_code: R01
ic: HL
serial_number: 088389
suffix: A1
program_official: SRINIVAS, POTHUR R
project_start_date: 2008-03-06
project_end_date: 2013-02-28
study_section: Vascular Cell and Molecular Biology Study Section[VCMB]
contact_pi_person_id: 8664760
contact_pi: GUO, ZHENHENG
other_pis: Not Applicable
congressional_district: 06
department: PHYSIOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
project_terms:
Affect;Agonist;Animal Model;Animals;Aorta;Biological Assay;Blood Pressure;Blood Vessels;Cardiovascular Diseases;Cardiovascular system;Cell physiology;Data;Development;Diabetes Mellitus;Diabetes Mellitus Non-Insulin-Dependent;Diabetic Angiopathies;Diet;Exhibits;Fatty acid glycerol esters;GTP-Binding Proteins;Genetic;Glucose;Goals;Hypertension;Knock-out;Lead;Link;Measurement;Mediating;Mesenteric Arteries;Mice Knockout;Mice Transgenic;Molecular;Molecular Weight;Morbidity - disease rate;Mortality Vital Statistics;Mus;Muscle Contraction;Muscle Smooth Vascular;Myocytes Smooth Muscle;NAD(P)H oxidase;Oligonucleotides Antisense;PLA2G6 protein human;Pathway interactions;Patients;Personal Satisfaction;Phospholipase A2;Phosphoric Monoester Hydrolases;Play;Prevention;Production;Protein Kinase C;Protein Overexpression;Proteins;Rate;Reactive Oxygen Species;Rho-associated kinase;Role;Scheme;Superoxides;Telemetry;Testing;Tissues;Transgenic Organisms;Vascular Smooth Muscle Tissue;db/db mouse;diabetic;feeding;in vivo;inhibitor/antagonist;leptin receptor;member;novel;novel therapeutics;response;therapeutic target


application_id: 7373335
project_number: 3M01RR002602-22S1
project_title: General Clinical Research Center
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
program_official: WILDE, DAVID B
project_start_date: 1985-09-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
contact_pi_person_id: 8535924
contact_pi: PERMAN, JAY A
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
DESCRIPTION: State the application's broad'long-term objectives and specific aims making reference to the health relatedness of the project. Describeconcisely the research design and methods for achieving these goals. Avoid summaries of past accomplishments and the use of the first person. This description is meant to serve as a succinct and accurate description of the proposed)work when separated from theapplication. If the application is funded this Fhe GCRC at the University of Kentucky is located on the 5th floor of the AB ChandlerMedicalCenter. This is the only clinicalresearch center in the state of Kentucky. It supportsethical multidisciplinary clinical research by a large number of investigators across the UK campus. Its mission includes search for knowledge of prevention andtreatment of disease teaching and training of clinical investigators. It supportsa broad spectrum of projects in Aging Alzheimer's disease BehavioralScience Metabolic Bone diseases HTV/AIDs neurological disordersdigestive disorders substanceabuse andwomen's health. Through its existence infrastructure is provided for $48million in research grants of the theUniversity of KentuckyMedical Center. This proposal requests continuing 5 years ofsupport for the continued growthand expansionof GCRC activities at the University of Kentucky.' We submit a substantial record of progress associatedwith recruitment of a new leadership team. There is a 35%increase in active proposals since the recruitment of thenewProgram Director. This has been accomplished by; 1)providingresource and proactivelyencouraging new clinicalinvestigators; 2) widelypublicizing the GCRC its outstandingpatient care staff; 3) initiatingthe expanded CoreLaboratories that consists of the data safety and analysis laboratory biochemical assaylaboratoryunit new exercisephysiology laboratoryunit and a bone histomorphometry laboratory unit to serve many activeprotocols within the UKGCRC as well as outside GCRCs; 4) integration of advance education with the K-30ClinicalResearch TrainingProgram; 5)continuation of excellent mentoring program to clinical investigators; 6) initiating the liaison betweenclinical andbasic science research at UK; and 7) focus on clinical 'and translational research. The continued supportalong theselines will enable the GCRC to remain an important focal center of clinical investigation at the UniversityofKentucky andthe GommmonwealthState of Kentucky. Moreover' the initiatives proposedin the proposal willpositionthe UK GCRC as a resource for other GCRCs around the country j description asis will become public information. Therefore do not include proprietary/confidential information. 00 NOT


application_id: 7373045
project_number: 1R01NS058382-01A1
project_title: Cellular Nucleic Acid Binding Protein (CNBP) in Aging and Disease
administering_ic: NINDS
award_notice_date: 2007-09-28
opportunity_number: PA-07-070
application_type: 1
activity_code: R01
ic: NS
serial_number: 058382
suffix: A1
program_official: REFOLO, LORENZO
project_start_date: 2007-09-30
project_end_date: 2012-03-31
study_section: Chronic Dysfunction and Integrative Neurodegeneration Study Section[CDIN]
contact_pi_person_id: 8535896
contact_pi: MURPHY, MICHAEL PAUL
other_pis: Not Applicable
congressional_district: 06
department: BIOCHEMISTRY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
project_terms:
Aging;Alzheimer's Disease;Amyloid;Amyloid beta-Protein Precursor;Amyloid deposition;Animal Model;Automobile Driving;Binding Proteins;Binding Sites;Biochemical;Biological;Biological Models;Brain;Cell Culture System;Cell physiology;Cells;Cultured Cells;Data;Degenerative Disorder;Deposition;Development;Disease;Drug Industry;Enzymes;Event;Foundations;Future;Generations;Genes;Genetic;Health;Human;In Vitro;Introns;Investigation;Knowledge;Lead;Link;Mediator of activation protein;Muscular Dystrophies;Myopathy;Myositis Inclusion Body;Myotonic Dystrophy;Nucleotides;Pathogenesis;Pathology;Peptides;Peripheral;Process;Protein Binding;Protein Overexpression;Proteins;RNA;RNA Messenger;RNA-Binding Proteins;Rate;Regulation;Role;Site;Skeletal system;Staging;Testing;Therapeutic;Title;ZNF9 protein human;age related;amyloid peptide;base;beta-site APP cleaving enzyme 1;beta-site APP cleaving enzyme 2;design;improved;in vivo;inhibitor/antagonist;insight;knock-down;mouse model;normal aging;novel;peptide A;secretase


application_id: 7373024
project_number: 1R21DA024401-01
project_title: Exploring the neurobiological response to anti-drug media messages with fMRI
administering_ic: NIDA
award_notice_date: 2009-06-19
opportunity_number: RFA-DA-07-007
application_type: 1
activity_code: R21
ic: DA
serial_number: 024401
program_official: SIROCCO, KAREN
project_start_date: 2009-06-20
project_end_date: 2011-05-31
study_section: Special Emphasis Panel[ZDA1 MXG-S (18)]
contact_pi_person_id: 1911365
contact_pi: JOSEPH, JANE E
other_pis: Not Applicable
congressional_district: 06
department: ANATOMY/CELL BIOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: Y
project_abstract:
DESCRIPTION (provided by applicant): Drug abuse is a major public health concern and preventing the onset of problematic drug use has become a public health priority. Individuals classified as high sensation seekers are vulnerable to drug abuse and other risky behaviors that may result in poor health outcomes. Sensation seeking is a biologically based personality trait marked by a tendency to seek out and engage in novel and varied experiences to maintain an optimal level of arousal -- even if those experiences involve significant risk. Prevention programs that use televised public service announcements (PSAs) tailored for high sensation seekers have been effective at motivating behavior and attitude change by incorporating elements of novelty and high sensation value that attract and hold the attention of the viewer. Although progress has been made with targeted prevention campaigns the cognitive and neurobiological mechanisms involved in effecting attitude change have not been addressed in depth. The present application uses state-of-the-art functional magnetic resonance imaging (fMRI) to explore the neurobiological systems involved in processing high sensation value PSAs by high and low sensation seeking individuals. This study will determine whether the neural substrates of processing PSAs overlap with the novelty detection / seeking dopamine reward system or whether the neural substrates overlap with brain systems involved in autonomic arousal and emotional regulation. Given that adolescence is a fairly vulnerable period for initial drug use frequency of use and development of abuse the present study includes two age groups -- adolescents and young adults. fMRI is an ideal technique for exploring the neural systems involved in processing complex media messages like PSAs due to its non-invasive nature and capacity to reveal large scale activation patterns that reflect the participation of numerous brain systems which are likely engaged with complex message processing. The characterization of different brain systems is accomplished with two commonly used tasks - novelty detection and emotional induction - in conjunction with the processing of PSAs that vary in sensation value (high and low) and thematic content (substance abuse versus safe sex). The PSAs used in this study were designed to reach high sensation seekers and have been shown previously to effect attitude change in adolescents. The PSAs are well characterized in terms of sensation value. The research proposed in this application will provide a foundation for generating hypotheses about potential neurobiological and cognitive mechanisms involved in effecting attitude or behavior change through anti-drug PSAs. Uniting community behavioral and neurobiological programs of research will provide a means of further identifying and increasing the effectiveness of prevention messages. Characterizing the brain systems involved in processing anti-drug media messages in individuals who are likely to try drugs can lead to a better understanding of how to design prevention messages in the future. A better understanding of the neural systems involved can lead to creative ways to invoke attitude and behavior change in these individuals.

project_terms:
Address;Adolescence;Adolescent;Affective;Arousal;Arts;Attention;Attitude;Behavior;Behavioral;Brain;Brain region;Cognitive;Communities;Complex;Detection;Development;Dopamine;Drug abuse;Drug usage;Effectiveness;Elements;Emotional;Esthesia;Eye;Foundations;Frequencies (time pattern);Functional Magnetic Resonance Imaging;Future;Health;Individual;Intervention Studies;Lead;Maps;Media Campaign;Nature;Neurobiology;Outcome;Pattern;Personality Traits;Pharmaceutical Preparations;Prevention;Prevention approach;Prevention program;Process;Regulation;Research;Rewards;Risk;Risk Behaviors;Role;Safe Sex;Services;Stimulus;Substance abuse problem;System;Techniques;Vulnerable Populations;age group;base;behavior change;design;experience;field study;indexing;information processing;motivated behavior;neurobiological mechanism;novel;novelty processing;prevent;programs;public health medicine (field);public health priorities;relating to nervous system;response;sample fixation;sex;young adult


application_id: 7372429
project_number: 1R01HL082835-01A2
project_title: The role of Prostaglandin E2 in Angiotensin II-induced vascular disease
administering_ic: NHLBI
award_notice_date: 2008-01-23
opportunity_number: PA-07-070
application_type: 1
activity_code: R01
ic: HL
serial_number: 082835
suffix: A2
program_official: TOLUNAY, ESER
project_start_date: 2008-02-01
project_end_date: 2013-01-31
study_section: Atherosclerosis and Inflammation of the Cardiovascular System Study Section[AICS]
contact_pi_person_id: 8341067
contact_pi: KING, VICTORIA L
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
project_terms:
Abdomen;Abdominal aorta structure;Agreement;Aneurysm;Angiotensin II;Aortic Aneurysm Abdominal;Apolipoprotein E;Atherosclerosis;Attenuated;Binding (Molecular Function);Biological;Blood Vessels;Cardiovascular Diseases;Cells;Chronic;Class;Coxibs;Data;Development;Development Other;Dinoprostone;Disease;Disruption;EP4 receptor;Endothelial Cells;Epoprostenol;Event;Functional disorder;Grants Applications;Hematopoietic;Human;In Vitro;Incidence;Inflammation;Inflammation Mediators;Inflammatory;Infusion procedures;Macrophages Peritoneal;Matrix Metalloproteinases;Mediating;Mus;Myocytes Smooth Muscle;Normal tissue morphology;Numbers;Pathway interactions;Play;Production;Promotor (Genetics);Prostaglandin H2;Prostaglandin-Endoperoxide Synthase;Prostaglandins;Prostaglandins I;Protein Isoforms;Publishing;Receptors Epoprostenol;Role;Staging;Suggestion;Tamoxifen;Testing;Therapeutic;Thinking function;Tissues;Vascular Diseases;attenuation;autocrine;cardiovascular risk factor;cyclooxygenase 1;cyclooxygenase 2;cytokine;in vivo;low density lipoprotein inhibitor;macrophage;paracrine;prostaglandin E synthase;prostaglandin E synthase-1;protective effect;receptor;response


application_id: 7372361
project_number: 1R01DK078175-01A1
project_title: A prevascularized islet immunoisolation device
administering_ic: NIDDK
award_notice_date: 2008-03-27
opportunity_number: PA-07-070
application_type: 1
activity_code: R01
ic: DK
serial_number: 078175
suffix: A1
program_official: APPEL, MICHAEL C
project_start_date: 2008-04-01
project_end_date: 2012-03-31
study_section: Hypertension and Microcirculation Study Section[HM]
contact_pi_person_id: 7715841
contact_pi: WILLIAMS, STUART K
other_pis: Not Applicable
congressional_district: 03
department: NONE
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: ORGANIZED RESEARCH UNITS
organization_zip: 402920001
organization_country: UNITED STATES
project_terms:
Address;Animal Model;Autologous;Beta Cell;Biocompatible Materials;Blood Circulation;Cell Survival;Cell Transplantation;Cell physiology;Cells;Chronic;Clinical;Clinical Trials;Collagen;Development;Devices;Diabetes Mellitus;Diabetes Mellitus Insulin-Dependent;Encapsulated;Endothelial Cells;Environment;Evaluation;Failure (biologic function);Fatty acid glycerol esters;Gel;Generations;Goals;Graft Survival;Healed;Hybrids;Hyperglycemia;Insulin;Islet Cell;Islets of Langerhans;Islets of Langerhans Transplantation;Knowledge;Laboratories;Lead;Measurement;Metabolic;Methods;Microcirculation;Modification;Molecular;Morbidity - disease rate;Mortality Vital Statistics;Natural immunosuppression;Nutrient;Organ;Organ Transplantation;Patients;Perfusion;Perfusion Regional;Pharmaceutical Preparations;Physiological;Postoperative Period;Recruitment Activity;Replacement Therapy;Research;Research Personnel;Risk;Staging;Structure;Supporting Cell;Surface;System;Technology;Testing;Therapeutic immunosuppression;Therapy Cell;Time;Tissue Engineering;Tissues;Transplantation;Transplants Cell;Vascular blood supply;Work;angiogenesis;base;beta cell replacement;design;diabetic;healing;implantation;improved;islet;mouse model;neovascularization;new technology;novel;pancreas allograft;response;yeast two hybrid system


application_id: 7372208
project_number: 1R21CA120693-01A2
project_title: Cryopreparation of PBMC for Immunotherapy and Immune Assessment Studies.
administering_ic: NCI
award_notice_date: 2008-04-28
opportunity_number: RFA-CA-07-037
application_type: 1
activity_code: R21
ic: CA
serial_number: 120693
suffix: A2
program_official: RUBINSTEIN, YAFFA
project_start_date: 2008-05-01
project_end_date: 2010-04-30
study_section: Special Emphasis Panel[ZCA1 SRRB-3 (O1)]
contact_pi_person_id: 1870178
contact_pi: YANNELLI, JOHN R.
other_pis: Not Applicable
congressional_district: 06
department: MICROBIOLOGY/IMMUN/VIROLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
project_abstract:
DESCRIPTION (provided by applicant):  There are many immunotherapy trials being conducted throughout the world ranging from vaccines to T cell transfer and antibody studies. In these trials aside from the obvious need to assess clinical responses Investigators must analyze changes in immune responsiveness which results from the immune intervention. Thus there is a need to collect PBMC from patients at regular intervals both before and following the therapy. These PBMC are cryopreserved to save the PBMC phenotype and function until a later time point when the PBMC can be thawed and assessed to determine if the immunotherapy was effective. In addition preparation of subsequent doses benefits from a source of readily obtainable PBMC which will respond to in vitro manipulation similar to the day the product was received by the lab. There are few standardized techniques available for cell cryopreservation as it relates to immunotherapy. Most labs have their own protocols which themselves often provide inconsistencies in cell viability and function upon thawing. It is also difficult to evaluate results of immunotherapy trials and make comparisons from lab to lab. The current proposal will focus on cryopreservation medium and compare static vs. controlled rate freezing techniques. In 4 Specific aims we will examine: 1) optimum medium for cryopreservation. Human serum + DMSO will be compared to Plasmalyte-A an FDA approved commercial serum free electroyte or rehydration fluid. The comparison of Plasmalyte A to serum is important because if it works significant cost reduction will occur since the cost per liter is less than 1% of the cost of serum. In addition this is an FDA approved product which is consistent from batch to batch. The second specific aim will evaluate different methods of thaw. Specific Aim 3 will compare static freeze techniques to controlled rate freezing. The fourth specific aim will monitor Specific aims 1 and 3 by comparing PBMC subset function at various time intervals using assays of cellular immunity. The goal of the proposal will be to develop a strategy for peripheral blood mononuclear cell (PBMC) cryopreservation which can be more universally applied. A more standardized approach will allow a more accurate assessment of immne responsivenss which can be compared between studies in different centers. In addition other clinical studies utilizing PBMC can also benefit from such a study (studies of HIV and transplantation for instance). The 4 specific aims will be done over a two year period of time.

project_terms:
Acute;Address;Aftercare;Antibodies;Area;Biological Assay;Blood;Boxing;Cell Survival;Cell physiology;Cells;Cellular Assay;Clinical;Clinical Research;Clinical Trials;Condition;Cryopreservation;Culture Media Serum-Free;Dendritic Cells;Dimethyl Sulfoxide;Dose;Effector Cell;Electrolytes;Ensure;Freezing;Gases;Glucose;Goals;Guanosine Monophosphate;HIV;Histology;Human;Immune;Immune response;Immunity Cellular;Immunologics;Immunotherapy;In Vitro;Intervention;Investigation;Kentucky;Laboratories;Learning;Leukapheresis;Licensing;Liquid substance;Lymphokine-Activated Killer Cells;Malignant Neoplasms;Measures;Mechanics;Methodology;Methods;Monitor;Natural Killer Cells;Nitrogen;Patients;Peripheral;Peripheral Blood Mononuclear Cell;Phase;Phenotype;Plasmalyte A;Preparation;Procedures;Process;Property;Protocols documentation;Protocols Treatment;Purpose;Range;Rate;Reagent;Rehydrations;Reliability of Results;Research Personnel;Running;Sampling;Serum;Site;Solutions;Source;Standards of Weights and Measures;T-Lymphocyte;Techniques;Temperature;Testing;Therapeutic;Time;Transplantation;United States;United States Food and Drug Administration;Universities;Vaccines;Variant;Viral;Work;cell preparation;clinical research site;cost;crystalloid;day;human study;in vivo;innovation;insight;melanoma;precursor cell;research clinical testing;research study;response;time interval;tumor


application_id: 7371426
project_number: 2R01AG019241-06A2
project_title: Prevention of Alzheimer's Diseae by Vitamin E and Selenium
administering_ic: NIA
award_notice_date: 2008-03-31
opportunity_number: PA-07-070
application_type: 2
activity_code: R01
ic: AG
serial_number: 019241
suffix: A2
program_official: RYAN, LAURIE M
project_start_date: 2001-09-30
project_end_date: 2013-02-28
study_section: Neurological, Aging and Musculoskeletal Epidemiology Study Section[NAME]
contact_pi_person_id: 1894359
contact_pi: MARKESBERY, WILLIAM R
other_pis: Not Applicable
congressional_district: 06
department: OTHER HEALTH PROFESSIONS
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
project_terms:
Affect;African American;Age;Aging-Related Process;Alzheimer disease prevention;Alzheimer's Disease;Antioxidants;Authorization documentation;Clinical Trials;Cognitive;Country;Critiques;DNA;Data;Dementia;Dementia Vascular;Depth;Diagnostic Procedure;Disease;Double-Blind Method;Early treatment;Effectiveness;Elderly;Etiology;Evaluation;Event;Frontotemporal Dementia;Funding;Goals;Incidence;Individual;Lewy Body Disease;Lipid Peroxidation;Lipids;Malignant neoplasm of prostate;Measures;Methodology;Minority;Monitor;National Cancer Institute;Nerve Degeneration;Neurodegenerative Disorders;Numbers;Oxidative Stress;Participant;Pathogenesis;Phase;Play;Population;Prevalence;Prevention;Preventive;Prostate Cancer Prevention Trial;Proteins;RNA;Randomized Controlled Trials;Range;Recruitment Activity;Research Personnel;Research Project Grants;Role;Screening procedure;Selenium;Selenium and Vitamin E Efficacy Trial;Selenium/vitamin E;Solid;Staging;Supranuclear Palsy Progressive;United States;Vitamin E;age effect;base;cognitive function;corticobasal degeneration;cost;disorder prevention;ethnic minority population;experience;men;men's group;mild cognitive impairment;normal aging;oxidation;prevent;research clinical testing;treatment duration


application_id: 7371014
project_number: 5R01DE018292-02
project_title: Oral Pathogen Exploitation of Innate Recognition as a Function of Age
administering_ic: NIDCR
award_notice_date: 2008-02-27
opportunity_number: RFA-DE-07-004
application_type: 5
activity_code: R01
ic: DE
serial_number: 018292
program_official: LUNSFORD, DWAYNE
project_start_date: 2007-03-06
project_end_date: 2012-02-28
study_section: ZDE1-YL(20)
contact_pi_person_id: 6712964
contact_pi: HAJISHENGALLIS, GEORGIOS
other_pis: Not Applicable
congressional_district: 03
department: DENTISTRY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF DENTISTRY/ORAL HYGN
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_terms:
1-Phosphatidylinositol 3-Kinase;16p;Adhesives;Age;Aging;Bacteroides thetaiotaomicron;Binding (Molecular Function);Biochemical;Birth;Bone Resorption;CD18 Antigens;Category Rating Scale;Chronic;Clinical;Complex;Data;Development;Dominant-Negative Mutation;Down-Regulation;Elderly;Event;Fimbria of hippocampus;Genetic;Genitourinary system;Human;Immune;Immune response;Immune system;Immunity Natural;Infection;Inflammation;Inherited;Inhibition of Apoptosis;Integrins;Interleukin-12;Killings;Lead;Ligand Binding;Literature;Macrophage-1 Antigen;Mediating;Microbe;Modeling;Models Experimental;Molecular;Mus;Oral cavity;Oral mucous membrane structure;Organism;Outcome;Pathway interactions;Pattern;Pattern Recognition;Pattern recognition receptor;Periodontal Diseases;Periodontitis;Peritonitis;Pilum;Porphyromonas gingivalis;Predisposition;Process;Range;Receptor Signaling;Research Personnel;Resistance to infection;Role;Severities;Signal Pathway;Signal Transduction;Study models;Surface;Techniques;Testing;Toll-Like Receptor 2;Virulence;Virulence Factors;age related;aged;base;concept;design;gastrointestinal;in vivo;inhibitor/antagonist;macrophage;microbial;microorganism interaction;monocyte;mutant;novel;oral pathogen;pathogen;receptor;receptor function;respiratory;response


application_id: 7371011
project_number: 5P01AG013494-10
project_title: CORE--DATA ANALYSIS
administering_ic: NIA
application_type: 5
activity_code: P01
ic: AG
serial_number: 013494
project_start_date: 2007-03-15
project_end_date: 2008-01-31
study_section: ZAG1
subproject_number: 9003
contact_pi_person_id: 8534364
contact_pi: ANDERSEN, ANDERS H
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2007-03-15
budget_end_date: 2008-01-31
project_abstract:
Dr. Anders H. Andersen will direct the Data Analysis Core. Dr. Andersen has over 15 years experience in biomedical signal and image data analysis especially in the area of MRI and fMRI data. He is familiar with the analysis of behavioral neurochemical morphological and electrochemical endpoints taken on aging rhesus monkeys. Dr. Hardy will be in charge of developing new MRI sequences for MRI data acquisition and MRI measurements of iron content. He is an expert on medical physics especially MRI. Dr. Rayens will be in charge of the statistical analysis for all major endpoints of the project as well as help with the correlation of responses among the projects and among measurements. He is an expert on biostatistics and appliedmultivariate statistical methods.  The specific aims of the Data Analysis Core are to:1. advise all investigators in the Program Project on issues related to experimental design and data analysis  2. perform the statistical analysis of the main endpoints in each of the projects3. provide quantitative assessments of each fMRI and anatomical MRI session recorded in Project by Zhang and  4. correlate the findings among the projects.

project_terms:
Aging;Area;Behavioral;Biometry;Charge;Data;Data Analyses;End Point;Experimental Designs;Image;Iron;Macaca mulatta;Magnetic Resonance Imaging;Magnetic Resonance Imaging Functional;Measurement;Medical;Physics;Research Personnel;Science of neurochemistry;Signal Transduction;Statistical Methods;data acquisition;experience;programs;response


application_id: 7371010
project_number: 5P01AG013494-10
project_title: CORE--ADMINISTRATIVE AND DATA MANAGEMENT
administering_ic: NIA
application_type: 5
activity_code: P01
ic: AG
serial_number: 013494
project_start_date: 2007-03-15
project_end_date: 2008-01-31
study_section: ZAG1
subproject_number: 9002
contact_pi_person_id: 8535427
contact_pi: GASH, DON MARSHALL
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2007-03-15
budget_end_date: 2008-01-31
project_abstract:
Core A is the data management and administrative core unit for the Program Project. The purpose of this core is to provide integration and administrative support for the other two cores and the three research projects. In addition this core will maintain fiscal accountability for the program project and facilitate data entry into the central data base. Core A in collaboration with Core C (the Data Analysis Core) will manage the computer network linking all investigators for collecting pooling collating analyzing and sharing data between projects.

project_terms:
Accountability;Age;Alzheimer's Disease;Animal Testing;Animals;Area;Behavioral;Bone Morphogenetic Proteins;Brain;British Columbia;Budgets;California;Cell Count;Cholinergic Receptors;Cognition Disorders;Collaborations;Communication;Computer Systems;Computer Workstations;Computer information processing;Critiques;Cues;Daily;Data;Data Analyses;Data Collection;Databases;Doctor of Medicine;Doctor of Philosophy;Educational workshop;Environmental Health;Evaluation;Faculty;Funding;Georgia USA;Georgia Western Asia;Growth;Health;Health behavior;Human;Human Resources;Hygiene;Image Analysis;In Situ;Inflammation;Institutes;Kindling (Neurology);Laboratories;Language Development;Learning;Link;Macaca;Magnetic Resonance Imaging;Magnetic Resonance Imaging Functional;Measurement;Medical center;Meetings Group;Memory Short-Term;Molecular;Monitor;Monkeys;Motion;Movement;Neurobiology;Neurologic;Neurology;Neurons;Neurosciences;Operative Surgical Procedures;Pattern;Pediatric Radiology;Pharmacology;Pharmacology and Toxicology;Philosophy;Physics;Physiology;Policies;Postdoctoral Fellow;Program Research Project Grants;Psychiatry;Purpose;Rattus;Recommendation;Records;Regulation;Research;Research Personnel;Research Project Grants;Retrieval;Role;Schedule;Schools;Schools Medical;Science of Anatomy;Science of neurochemistry;Series;Spectrum Analysis;Students;Study Interdisciplinary;System;Technology;Travel;Universities;Veterans;Work;axon guidance;behavior test;case history;college;computer network;cost effective;data management;experience;ferrosoferric oxide magnetite;forest;journal article;member;nonhuman primate;professor;programs


application_id: 7371009
project_number: 5P01AG013494-10
project_title: CORE--PRIMATE FACILITY
administering_ic: NIA
application_type: 5
activity_code: P01
ic: AG
serial_number: 013494
project_start_date: 2007-03-15
project_end_date: 2008-01-31
study_section: ZAG1
subproject_number: 9001
contact_pi_person_id: 2154561
contact_pi: ZHANG, ZHIMING
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2007-03-15
budget_end_date: 2008-01-31
project_abstract:
Core B is the Primate Core Facility. It is responsible for the management of all nonhuman primates used in the program project. The services provided by Core B include supervision of all surgical procedures and MRI sessions. In addition Core B will maintain animal case histories schedule animal utilization between projects and collect brain tissue samples for analysis during autopsy.

project_terms:
Animals;Autopsy;Core Facility;Magnetic Resonance Imaging;Operative Surgical Procedures;Primates;Schedule;Services;Supervision;Tissue Sample;brain tissue;case history;nonhuman primate;programs


