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Kathleen A. Martin, Ph.D.

Contact Information:

Professional Interests:

The molecular mechanisms that regulate vascular smooth muscle cell (VSMC) phenotype.

Dr. Martin received her B.A. in Biology from Hiram College in 1990, and a Ph.D. in Physiology and Biophysics from Case Western Reserve University in 1996. She completed her postdoctoral training at Harvard Medical School in the Departments of Medicine and Cell Biology. Dr. Martin joined the Dartmouth faculty in the Department of Surgery (Vascular Section) in 2000, and the Department of Pharmacology and Toxicology in 2001.

Our studies are aimed at determining the molecular mechanisms that regulate vascular smooth muscle cell (SMC) phenotype. Mature SMC are unique among myocytes in their ability to de-differentiate and re-enter the cell cycle. This is essential for such processes as angiogenesis, but also contributes to the pathologies of atherosclerosis, intimal hyperplasia, and restenosis. Our close collaboration with Drs. Richard Powell and Eva Rzucidlo in Vascular Surgery at Dartmouth-Hitchcock Medical Center allows us to address important issues in translational cardiovascular research, using samples from affected patients.

Rapamycin/mTOR/Akt signaling: Recently, rapamycin eluting stents have revolutionized treatment of coronary artery disease, dramatically reducing restenosis in these vessels. However, the risk of late stent thrombosis has somewhat reduced enthusiasm for this treatment. We are investigating novel signaling pathways and transcriptional mechanisms by which rapamycin promotes vascular SMC differentiation, in hopes of identifying key molecular events that may serve as smooth muscle specific therapeutic targets for prevention of atherosclerosis and intimal hyperplasia, in order to minimize adverse effects. We are also investigating a potential link between adipocyte-derived hormones, obesity, mTOR, and vascular smooth muscle phenotype, and the mechanisms by which second hand smoke exposure may perturb this balance and promote cardiovascular disease.

Communication between vascular endothelial and smooth muscle cells: Endothelial cell (EC) dysfunction or injury is a major cause of atherosclerosis and intimal hyperplasia/restenosis. Our laboratory has shown that co-culturing vascular SMC opposite EC promotes SMC differentiation, and that this effect is mediated by an EC-derived soluble mediator. We are currently working to identify this mediator(s), and the signaling pathways and target transcription factors by which endothelial cells influence SMC phenotype.

Prostacyclin regulation of smooth muscle contractile proteins: Our laboratory is also studying how prostacyclin, an EC-derived prostaglandin product of COX-2, promotes vascular SMC differentiation through transcriptional mechanisms, in close collaboration with Dr. John Hwa (Pharm-Tox, Cardiology). These studies have identified a novel mechanism underlying prostacyclin’s cardioprotective effects, which may contribute to the adverse cardiovascular events attributed to COX-2 inhibitors such as rofecoxib (Vioxx). These observations have led us to another exciting project in collaboration with Dr. Roger Young (Ob/Gyn) studying the role of prostacyclin in regulating contraction and induction of labor in human uterine smooth muscle.

Courses Taught:

PEMM 101/102 Core Course in Experimental Molecular Medicine, Course Director
Pharm 215 Medical Pharmacology
Pharm 129 Molecular Pharmacology
Pharm 127 Pathophysiology
PEMM 275 Vascular Biology

Grant Information:

NCCC Prouty Pilot Project Grant 2007-2008
NIH NHLBI R01 1R01HL091013 2008-2013
FAMRI Clinical Innovator Award 2008-2011