Lawrence Brass, M.D. Ph.D. Medline search
Professor of Medicine, Pathology and Pharmacology
Associate Director, Center for Experimental Therapeutics
Associate Dean and Director, Combined Degree and Physician Scholars Programs, University of Pennsylvania, School of Medicine
Member, Graduate Group in Pharmacological Sciences
Member, Cell and Molecular Biology Graduate Group
Member, Biochemistry and Molecular Biophysics Graduate Group
Ph.D. (Biochemistry), 1975, Case Western Reserve University
M.D., 1977, Case Western Reserve University

Biomedical Research 2 (BRB II/III), Rm. 913
421 Curie Blvd.
Philadelphia, PA 19104-6160

215-573-3540 phone
215-573-2189 fax

Research:
The studies in my laboratory focus on the molecular mechanisms underlying vascular biology and pathology. Despite major medical advances over the past 20 years, atherosclerotic cardiovascular disease and vascular thrombosis remain among the major causes of death and chronic illness in the United States. Our studies are directed toward understanding the intracellular events that underlie these disorders in vascular cells. To do this, we study the molecular mechanisms of signal transduction that allow platelets to respond to extracellular events. A variety of approaches are being used included transgenic and knockout mouse models.

Topics that we currently have under investigation include: 1) Protease-activated G protein coupled receptors, including the thrombin receptor. These are a widely-expressed family of receptors that are activated by proteases. Three family members have been described to date. Our work focuses on the identification of additional family members, the signalling pathways that are initiated when these receptors are activated, the trafficking of the receptors within the cell as used receptors are replaced, and the development of receptor antagonists and clinically-useful assays for detecting receptor activation in vivo. 2) The role of the G protein, Gz. G proteins are molecular switches that activate or retard the intracellular events that regulate cell function. Although most G proteins are expressed in most tissues, a few are expressed only in a limited number of tissues. Gz is one of the G proteins that are not universally expressed, its presence being limited mainly to some neural cells and to some hematopoietic cells, particularly megakaryocytes and platelets. We have recently completed the development of mice that lack the a subunit of Gz. These mice have a disorder of platelet function that is able to protect them from the mortality and morbidity in acute thrombosis models. 3) The role in platelet activation and endothelial cell biology of Eph tyrosine kinase receptors and their ligands, which are known as ephrins. Eph receptors are a large family of membrane-bound tyrosine kinases whose function is largely unknown. Recent studies have shown that interactions between Eph receptors and their ligands play an important role in the developing central nervous system. Our interest lies in their potential role in the vascular wall, participating in interactions that occur when platelets, endothelial cells and leukocytes encounter each other.

Keywords: vascular biology, thrombosis, atherosclerosis, signal transduction, platelets, endothelial cells, G protein coupled receptors, integrins.

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