Grants and Contracts Details
Description
The applicant for this NIH Diversity K01 (RFA-HL-19-026) application is Dr. Mary Sheppard, an Assistant
Professor at the University of Kentucky, College of Medicine. Dr. Sheppard’s area of research interest is
Marfan syndrome, and she has established an Aortic Clinic in the Department of Surgery. Her long term career
goal is to develop new therapeutics for thoracic aortic aneurysm. This decision was influenced by her personal
challenges with this diagnosis. Desiring more treatment options, Dr. Sheppard has decided to embark on
additional training in basic science research. Her short term goals, which form the basis for the research plan,
are: (1) to develop preclinical research skills that will enable her to identify new therapeutic targets to treat
vascular diseases; (2) to establish herself as an expert in aneurysm research; and (3) to submit an R01
funding application upon this project’s completion. Dr. Sheppard has assembled an impressive mentoring team
composed of Drs. Daugherty, Cassis, Graf, and Milewicz. Her primary mentor, Dr. Daugherty, has extensive
expertise in animal models of aneurysm formation, and he has been a successfully funded NIH investigator for
several decades. Co-mentor Dr. Lisa Cassis is an expert in the renin-angiotensin system and sexual
dimorphism of aortic aneurysms. Co-mentor Dr. Greg Graf is an expert in cholesterol metabolism and statin
pharmacology. Dr. Dianna Milewicz, an expert in medical genetics, has a career in translational studies
focused on genetic predisposition to vascular diseases. All mentors are senior scientists with a track record of
successfully mentoring new faculty to independent NIH funding. This mentor team will assist Dr. Sheppard in
learning laboratory techniques which include ultra-high resolution microscopy, FACS, and biochemical
fractionation of farnesylated proteins. The proposed research will examine the mechanisms by which statins
attenuate thoracic aortic aneurysm growth in a mouse model of Marfan syndrome. The impact of Ras
farnesylation on aneurysm growth, matrix metalloproteinase activity, elastin fragmentation, and leukocyte
accumulation will be evaluated in Aim 1. The impact of statin combined with beta-blocker or angiotensin
receptor blocker in thoracic aortic aneurysm will be investigated in Aim 2. The findings of these studies will
form the preliminary data for an R01 research application which will transition Dr. Sheppard from trainee status
to independent physician-scientist.
Status | Active |
---|---|
Effective start/end date | 12/18/20 → 11/30/25 |
Funding
- National Heart Lung and Blood Institute: $486,000.00
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