Jeffrey Alexis, M.D.
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Jeffrey Alexis, M.D.
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Research
- The Role of Bcr kinase in PDGF-mediated effects in vascular smooth muscle.
Background
Dr. Alexis earned his M.D. from Harvard University in 1992. He was an intern and resident from 1992- 1995 at the Massachusetts General Hospital and completed his cardiology fellowship in 1998 at the Mount Sinai School of Medicine. He is Board Certified in Internal Medicine and Cardiovascular Disease. He served on the faculty of the Mount Sinai School of Medicine (1998-2003) and joined the faculty of the University of Rochester in 2003 as an Assistant Professor of Medicine. Dr. Alexis is a member of the heart failure/transplant section and his research focuses on signaling pathways that regulate transplant arteriopathy.
Research Overview
The research in my lab focuses on key signaling pathways involved in the development of transplant arteriopathy. Transplant arteriopathy is the leading cause of long term morbidity and mortality following heart transplantation. Histopathology reveals intimal proliferation. Animal models have shown that there is an early inflammatory response to transplant characterized predominantly by macrophage and lymphocyte accumulation within the graft. Subsequently intimal proliferation develops- an accumulation of smooth muscle cells and inflammatory cells. Recent studies have suggested that some of these intimal cells may be bone marrow precursor cells. The focus of our current research proposal is the role of peroxisome proliferator-activated receptors (PPARs) on the development of transplant arteriopathy. Peroxisome proliferator-activated receptors have been shown to exert anti-inflammatory activities in vascular and immunological cells including endothelial cells, vascular smooth muscle cells and monocytes. There are several different PPAR isoforms including PPAR-a, PPAR-g, and PPAR-b/d. We are utilizing cell culture data and animal models to assess the effect of peroxisome proliferator-activated receptors on the development of transplant arteriopathy. We hypothesize that absence of these receptors will worsen arteriopathy a disease initiated by inflammation, and treatment with PPAR agonists will attenuate arteriopathy. Our initial work will focus on PPAR g and the gene Bcr. Recent data from our laboratory suggest that Bcr acts as a modulator of vascular smooth muscle cell activation by decreasing PPARg transcriptional activity and enhancing NF-kB transcriptional activity. We are investigating the hypothesis that activation of PPARg and inhibition of Bcr will attenuate transplant arteriopathy. Positive results are likely to have important implications in the treatment of patients undergoing transplantation.
Recent Publications
- Alexis JD, Lao CD, Selter JG, Courtney MC, Correa DK, Lansman SL, Kushwaha SS, Gass AL. Cardiac troponin T: A non-invasive marker for cardiac transplant rejection? J Heart Lung Transplant 1998;17:395-8.
- †Freudenberger R, †Alexis JD, Gass AL, Fuster V, Badimon J. Antithrombotic effect of FK 506 versus cyclosporine in cardiac transplant recipients: potential implications in transplant arteriopathy. J Heart Lung Transplant 1999 Dec;18(12):1228-31.
†contributed equally to this work - Alexis JD, Pyo RT, Chereshnev I. Immunologic factors in transplant arteriopathy: Insight from animal models. Mount Sinai Journal of Medicine. 2003;70:191-196.