Mark B. Taubman, M.D.
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Mark Taubman M.D.- Charles A. Dewey Professor and Chairman of Medicine Mark_Taubman@urmc.rochester.edu Primary Appointment: |
Research
- Vascular Smooth Muscle Cell Biology
- Tissue Factor Biology and the Regulation of Arterial Thrombosis
- Chemokine Biology
- Inflammatory Mechanisms in Atherosclerosis and Arterial Injury
- The Role of Prolyl Hydroxylases in Muscle Differentiation and Hypoxia
Research Overview
Dr. Taubman’s laboratory is focused on the role of vascular smooth muscle cells (SMC) in regulating inflammation and thrombosis in the arterial wall. There are three major areas of investigation: 1) Tissue factor, the initiator of coagulation, is highly regulated by growth factors in SMC and is induced in the arterial wall after balloon injury. Ongoing studies involve the regulation of tissue factor expression in SMC culture and the regulation of tissue factor expression and activity in the injured vessel wall and in animal models of atherosclerosis. Recent data has shown that tissue factor can be released from the cell wall in microparticles and that these particles retain the ability to activate coagulation. In addition, there is an alternatively spliced form of tissue factor that is soluble and circulates in the blood. We are trying to understand the role of these forms of circulating tissue factor in mediating arterial thrombosis using mice with tissue-specific tissue factor deletions and mice expressing only full-length or alternative-spliced forms of tissue factor. 2) MCP-1 encodes a monocyte chemoattractant that, like tissue factor, is regulated by growth factors in SMC culture and in the vessel wall after balloon injury. Ongoing studies involve examination of MCP-1 regulation in cell culture and in animal models of arterial disease. A particular focus has been the regulation of MCP-1 mRNA stability by PDGF and glucocorticoids. Studies are focused on identifying the proteins and signaling pathways that regulate MCP-1 mRNA stability. Such studies may provide novel approaches to attenuate the inflammatory process. 3) EGLN3/SM-20 encodes an intracellular prolyl hydroxylase that regulates the response of cells to hypoxia. We have recently determined that EGLN3 also plays a key role in muscle cell differentiation and are currently exploring the mechanism underlying this finding. Studies are ongoing to elucidate the function of this gene using muscle cell cultures and by generating an EGLN3 knockout mouse. EGLN3 is also being analyzed using in vitro and in vivo models to examine its regulation in response to ischemia.
Recent Publications
- Schecter, A.D., Berman, A.B., Yi, L., Mosoian, A., McManus, C.M., Klotman, M.E., and Taubman, M.B. HIV envelope gp120 activates human arterial smooth muscle cells. Proc Natl Acad Sci, USA. 2001; 98:10142-10147.
- Roque, M., Kim, W.J.J., Gazdiou, M., Malik, A., Reis, E.D., Fallon, J.T., Badimon, J.J., Charo, I.F., and Taubman, M.B. CCR2 deficiency decreases intimal hyperplasia after arterial injury. Arterioscler, Thromb, Vasc Biol. 2002; 22:554-559.
- Schecter, A.D., Berman, A.B., Yi, L, Ma, H., Charo, I.F., and Taubman, M.B. MCP-1-Dependent Signaling in CCR2-/- Smooth Muscle Cells: Evidence for an Alternative MCP-1 Receptor. J. Leukoc. Biol. 2004, 75:1079-1085.
- Pyo, R., Jensen, K.K., Wiekowski. M.T., Manfra, D., Alcami, A., Taubman, M.B., and Lira, S.A. Inhibition of Intimal Hyperplasia in Transgenic Mice Conditionally Expressing the Chemokine Binding Protein M3. Am J Pathol. 2004, 164:2289-2297.
- Kodali, R.B., Kim, W.J.H., Galaria, I.I., Miller, C., Schecter, A.D.,Lira, S.A., Taubman, M.B. CCL11 (Eotaxin) Induces CCR3-Dependent Smooth Muscle Cell Migration. Arterioscler Thromb Vasc Biol. 2004, 24:1211-1216.
- Pyo, R.T., Mackman, N., and Taubman, M.B. Mice Deficient in Tissue Factor Demonstrate Attenuated Intimal Hyperplasia in Response to Vascular Injury and Decreased Smooth Muscle Cell Migration. Thrombosis Haemostasis. 2004, 92:451-8.
- Charo, I.F., and Taubman, M.B., Chemokines in the Pathogenesis of Vascular Disease. Circ Res 2004, 95:858-66.