WASHINGTON UNIVERSITY SCHOOL OF MEDICINE DEPARTMENT OF MEDICINE

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The goal of our research is an understanding of the initiation and control of hemostasis and the interrelationship between coagulation and inflammation. Rather than hemorrhagic phenomena, the investigative thrust concerns pathologic thrombosis and atherosclerosis.

Our investigations recently have centered on a novel endogenous coagulation inhibitor that circulates bound to plasma lipoproteins that we have isolated, cloned, expressed and characterized called Tissue Factor Pathway Inhibitor (TFPI). TFPI is a multivalent Kunitz-type proteinase inhibitor that directly inactivates coagulation factor Xa and produces feedback inhibition of the factor Vlla/tissue factor catalytic complex that is responsible for the initiation of coagulation. Additional work involves studies of a previously unrecognized pathway for coagulation factor XI activation and the characterization of a previously undetected regulator of coagulation we have termed the protein Z-dependent protein inhibitor. The aim of current studies is to define through both in vitro and in vivo experiments the role of coagulation in the inflammatory response and vascular diseases.

Work in the laboratory involves protein purification and characterization kinetics of proteinase/inhibitor interactions, production of monoclonal and polyclonal antibodies for the development of in vitro immunoassays and histochemical studies, expression and characterization of native and mutant recombinant proteins for structure/function studies, and the assessment of particular interventions in animal models using transgenic and gene deletion techniques.

Tissue factor pathway inhibitor (TFPI) inhibition of FVIIa/TF Two pathways for the factor (F)FXa-dependent inhibition of FVIIa/TF by TFPI are shown. On the right, soluble FXa generated by the FVIIa/TF catalytic complex is bound and inhibited by TFPI and then the FXa/TFPI complex binds FVIIa-TF forming a final quaternary FVIIa/TF-TFPI-FXa inhibitory complex. On the left, TFPI binds to a tertiary complex containing FVIIa/TF and FXa that has not yet dissociated from FVIIa/TF following its activation. Kinetic studies strongly suggest that the physiological effect of TFPI is predominantly mediated through this latter pathway. From: Broze GJ Jr The rediscovery and isolation of TFPI. J Thromb Haemost 2003 Aug;1(8):1671-5

Education

1968	BS Physics (Magna Cum Laude), University of Washington, Seattle, WA
1972	MD, University of Washington School of Medicine, Seattle, WA

Post-graduate Training

1972-1973	Intern in Medicine-Pediatrics, North Carolina Memorial Hospital, Chapel Hill, NC
1973-1974	Junior Assistant Resident in Pediatrics, North Carolina Memorial Hospital, Chapel Hill, NC
1974-1975	Junior Assistant Resident in Medicine, North Carolina Memorial Hospital, Chapel Hill, NC
1975-1976	Senior Assistant Resident in Medicine, North Carolina Memorial Hospital, Chapel Hill, NC
1976-1977	Clinical Fellow, Division of Hematology/Oncology, Washington University School of Medicine, St. Louis, MO
1977-1979	Research Fellow, Division of Hematology/Oncology, Washington University School of Medicine, St. Louis, MO

Academic Positions

1979-1980	Instructor of Medicine, Washington University School of Medicine, St. Louis, MO
1980-1987	Assistant Professor of Medicine, Washington University School of Medicine, St. Louis, MO
1987-1991	Associate Professor of Medicine, Washington University School of Medicine, St. Louis, MO
1991-present	Professor of Medicine, Washington University School of Medicine, St. Louis, MO
1992-present	Professor of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO
2005-present	Professor of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO

Appointments

1980-1990	Director, Transfusion Unit/Medicine Clinical Practice, Jewish Hospital, St. Louis, MO
1980-1988	Transfusion Review Committee, Jewish Hospital, St. Louis, MO
1986-1987	Transfusion Review Committee, Chairman Pro Tem, Jewish Hospital, St. Louis, MO
1988-1993	Human Studies Committee, Jewish Hospital, St. Louis, MO
1992-1999	Co-Coursemaster, Markey Special Emphasis Pathway in Human Pathobiology

Board Certification

Internal Medicine

Professional Societies

	Association of American Physicians
	American Society for Clinical Investigation
	American Society of Biological Chemists
	American Society of Hematology    Subcommittee on Thrombosis, 1991-1997       Chairman, 1992-1993, 1996-1997    Nominating Committee, 1999-2002       Chairman, 2000    Scientific Program Committee, 2000-2002       Co-Chairman, 2001
	American Heart Association: Thrombosis Council    Program Committee, 1988-1991    Executive Council, 1991-1994    Established Investigator Grant Review Committee, 1995-1998
	International Society on Thrombosis and Haemostasis    TFPI Subcommittee, Chairman, 1991-1993    Lectures/Awards Subcommittee, 2002-2005    Executive Council, 2002-2008    Publications Subcommittee, Chairman, 2003-present    Editor-in-Chief Search Committee, Chairman, 2005-2006
	National Heart, Lung and Blood Institute    Hematology Study Section-1, 2001-2003

Editorial Boards

1989-2008	Blood    Editorial Board, 1989-1994    Associate editor, 2003-2008
1990-1995	Arteriosclerosis and Thrombosis
1991-present	Current Opinion in Hematology, Hemostasis-Thrombosis Section Co-editor
1992-1996	Journal of Biological Chemistry

Honors & Awards

	Phi Beta Kappa
1979-1984	Clinical Scientist Award, American Heart Association
1991	Distinguished Investigator, International Society on Thrombosis and Haemostasis
1994	William Dameshek Prize, American Society of Hematology
1996	Sol Sherry Lecturer, American Heart Association
1995-present	Best Doctors/Top Docs in America
1996-present	Best Doctors/Top Docs in the Midwest
1999	Distinguished Career Award, International Society on Thrombosis and Haemostasis
2001	Pia Glas-Greenwalt Lecture, International Society on Thrombosis and Haemostasis

Updated: April 23, 2008