WASHINGTON UNIVERSITY SCHOOL OF MEDICINE DEPARTMENT OF MEDICINE

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Our laboratory is interested in defining the mechanisms by which cells respond to extracellular signals both to evoke intracellular responses and to modify the extracellular environment with specific reference to cells of blood and blood vessel walls. The laboratory utilizes techniques of biochemistry and molecular biology to study intracellular signaling reactions based on the inositol phosphate signaling pathway.

We have defined the pathways and functions involved in the phosphatidylinositol messenger-generating system. The phosphoinositides are minor phospholipids that undergo accelerated breakdown in response to extracellular agonists, such as small molecule effectors, peptide hormones and growth factors. A host of second-messenger molecules are produced, including derivatives of arachidonic acid, diacylglycerol and many inositol phosphates and phospholipids. We have recently discovered several new enzymes and metabolites involved in this pathway and are further exploring these and other new reactions. Enzymes are being isolated and characterized, and their role in the regulation of this complex pathway is under investigation. We have cloned and expressed several of these enzymes. Stable transfectants are being used to define messenger functions. We are exploring how these reactions link to better signaling systems or control cell growth and gene expression. Several of the enzymes of this pathway have recently been shown to be mutated as the cause of human diseases. Mutations in an isozyme of inositol polyphosphate 5-phosphatase cause Lowe syndrome that results in mental retardation, renal tubular acidosis and eye abnormalities. Inositol polyphosphate 4-phosphatase is required for megakaryocyte differentiation and platelet production.

Phosphatidylinositol signaling reactions From: Zhang X, Majerus PW Phosphatidylinositol signalling reactions. Semin Cell Dev Biol. 1998 Apr;9(2):153-60

Education

1958	BS, Notre Dame University, South Bend, IN
1961	MD (Magna Cum Laude), Washington University School of Medicine, St. Louis, MO

Post-graduate Training

1961-1963	Intern in Medicine and Assistant Resident in Medicine, Massachusetts General Hospital, Boston, MA
1963-1966	Research Associate, National Heart Institute, Laboratory of Biochemistry, Bethesda, MD

Academic Positions & Employment

1966-1975	Assistant Professor of Biochemistry, Washington University School of Medicine, St. Louis, MO
1966-1969	Assistant Professor of Medicine, Washington University School of Medicine, St. Louis, MO
1969-1971	Associate Professor of Medicine, Washington University School of Medicine, St. Louis, MO
1969-1970	NIH Biochemistry Fellowship Review Committee
1971-present	Professor of Medicine, Washington University School of Medicine, St. Louis, MO
1972-1977	Board of Directors, American Cancer Society, St. Louis City and County Unit
1973-1994	Co-director, Division of Hematology-Oncology, Washington University School of Medicine, St. Louis, MO
1974-1978	NIH Hematology Study Section
1976-present	Professor of Biochemistry, Washington University School of Medicine, St. Louis, MO
1981-1982	President, American Society for Clinical Investigation
1988-1993	Member, American Heart Association Research Committee
1988-present	Chairman, James S. McDonnell Foundation, Program for Molecular Medicine in Cancer Research
1989-1992	Chairman, National Academy of Sciences, Section 41, Medical Genetics, Hematology and Oncology
1989-1993	Chairman, Searle Scholars Program
1989-1994	Chairman, Board of Scientific Counselors NHLBI
1991	President, American Society of Hematology
1994-present	Co-Director, Division of Hematology, Washington University School of Medicine, St. Louis, MO
1994-1998	Counselor, Institute of Medicine
1994-1996	Vice-Chairman of Finance, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO
1996-2000	Member, Committee on Science, Engineering and Public Policy, National Academy of Science

Editorial Responsibilities

1970-1976	Member, Editorial Board, Journal of Clinical Investigation
1973-1977	Member, Editorial Board, Journal of Lipid Research
1976-1978	Member, Editorial Board, BLOOD, Journal of American Society of Hematology
1977-1982	Editor, Journal of Clinical Investigation
1981-1984	Member, Editorial Board, Archives of Biochemistry and Biophysics
1982-1987	Member, Editorial Board, The Journal of Biological Chemistry
1989-present	Member, Editorial Board, Proceedings of the National Academy of Sciences USA
1989-1994	Member, Editorial Board, The Journal of Biological Chemistry
1991-2001	Editorial Advisory Board, Biochemistr
1997-2002	Member, Editorial Board, The Journal of Biological Chemistry
2003-2008	Member, Editorial Board, The Journal of Biological Chemistry

Professional Societies

	Alpha Omega Alpha
	Sigma Xi
	American Society for Clinical Investigation
	American Society of Biological Chemists
	American Federation for Clinical Research
	American Society of Hematology
	Association of American Physicians
	Fellow, American College of Physicians
	Member, National Academy of Sciences
	Member, Institute of Medicine, National Academy of Sciences
	Fellow, American Academy of Arts and Sciences
	Fellow, Royal College of Physicians of Ireland

Honors & Awards

1959	Roche Award in Medicine, Washington University School of Medicine
1961	Smith, Kline and French Thesis Award
1961	Alpha Omega Alpha Prize, Washington University School of Medicine
1966-1971	American College of Physicians Teaching and Research Scholar
1966-1975	American Cancer Society Faculty Research Associate Award
1981	Dameshek Prize for Research, American Society of Hematology
1985	Distinguished Career Award for Contributions to Hemostasis, International Society for Thrombosis and Hemostasis
1986	Alumni/Faculty Award, Washington University School of Medicine
1987	Fellow, American Association for the Advancement of Science
1988	The Harvey Lectures Series
1988	Distinguished Lecturer Award of the Thrombosis Council, American Heart Association
1990	Lewis A. Connor Lecturer, American Heart Association
1991	Kober Lecture Award, Association of American Physicians
1994	The Robert J. and Claire Pasarow Foundation Award, Cardiovascular Research
1998	Bristol-Myers Squibb Award for Distinguished Achievement in Cardiovascular/Metabolic Research
1998	Distinguished Alumni Scholarship, Washington University School of Medicine
1999	Sol Sherry Distinguished Lecture in Thrombosis
2002	Nature Medicine/UCSD Award for Mentoring (with Stuart Kornfeld)
2003	Second Century Award, Washington University

Updated: March 20, 2008