WASHINGTON UNIVERSITY SCHOOL OF MEDICINE DEPARTMENT OF MEDICINE

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Hematopoiesis, the process by which all blood cells are formed, is a tightly regulated process that is disrupted in a number of blood diseases, including leukemias. The main interest of our laboratory is to define the mechanisms that regulate normal and leukemic hematopoiesis. Current projects include the following:

Identification of mutations contributing to therapy-related acute myeloid leukemia (t-AML).
We are applying next generation sequencing technologies to sequence the leukemic genomes of patients with t-AML. We intend to identify and biologically validate recurring mutations in t-AML.

Characterization of the role of microRNAs and other non-coding RNAs in leukemia.
There is emerging data suggesting that non-coding RNAs, in particular microRNAs (miRNAs), play an important role in the pathogenesis of human cancer. In our laboratory, we are using next generation sequencing technologies to identify and validate dysregulated and mutated miRNAs and other non-coding RNAs that contribute to transformation in leukemia.

Characterization of the pathogenesis of congenital neutropenia syndromes.
These syndromes are characterized by neutropenia at birth and are associated with a marked propensity to develop leukemia. Studies to define the molecular mechanisms of disease pathogenesis and leukemogenesis are underway.

Regulation of normal and malignant hematopoietic stem cells by the bone marrow microenvironment (stem cell niche).
Studies are underway to characterize how normal (and leukemic) stem cells interact with stromal cells in the bone marrow to regulate their function. In particular, we are studying how G-CSF alters the bone marrow microenvironment and leads to the mobilization of stem cells from the bone marrow to blood (see figure).

Mobilization of hematopoietic stem cells (HSCs) by G-CSF. At baseline, osteoblast lineage cells express key molecules that regulate HSC function and retention in the bone marrow, including CXCL12, VCAM-1, and kit ligand. Signaling in bone marrow monocytes initiates the mobilization cascade by suppressing osteoblasts. The loss of osteoblast lineage cells disrupts key interactions regulating HSPC function, including CXCR4, VLA-4, and c-kit signaling.

Education

1981	B.S., University of Wisconsin-Milwaukee, Milwaukee, WI
1985	M.D., University of Wisconsin-Madison, Madison, WI

Post-graduate Training

1984	Medical Research, NCI summer training award, NIH, Baltimore, MD
1985-1986	Intern in Medicine, Barnes Hospital, St. Louis, MO
1986-1988	Assistant Resident in Medicine, Barnes Hospital, St. Louis, MO
1988-1992	Hematology-Oncology Fellow, Washington University Medical Center, St. Louis, MO

Academic Positions

1993-1996	Instructor, Department of Medicine, Washington University Medical School, St. Louis, MO
1996-2003	Assistant Professor, Departments of Medicine and Pathology & Immunology, Washington University Medical School, St. Louis, MO
2003-2008	Associate Professor, Department of Medicine, Washington University Medical School, St. Louis, MO
2008-present	Professor, Departments of Medicine and Pathology & Immunology, Washington University Medical School, St. Louis, MO

Current Appointments & Committees

	Co-program leader, Hematopoietic Development and Malignancy Program, Siteman Cancer Center
	Co-leader, Translational Oncology Program at Washington University
	Member, Basic Science Leadership Committee, Siteman Cancer Center
	Markey Pathway Admissions and Steering Committee, Washington University
	MA/MD Program Admissions and Steering Committee, Washington University
	Summer Scholars Program in Biology and Biomedical Research Admissions Committee, Washington University

Board Certification

1989	Internal Medicines
1990	Hematology

Honors & Awards

1981	Kurt H. Vanselow Undergraduate Research Scholarship; University of Wisconsin-Milwaukee, Milwaukee, WI
1981	The American Institute of Chemists' Student Award; University of Wisconsin-Milwaukee, Milwaukee, WI
1981	Phi Beta Kappa; University of Wisconsin-Milwauikee, Milwuakee, WI
1981-1984	Outstanding Achievement Award by Promotion's Committee; University of Wisconsin-Madison Medical School, Madison, WI
1982	Academic Excellence Award (top 2% of class); University of Wisconsin-Madison Medical School, Madison, WI
1984	Alpha Omega Alpha; University of Wisconsin-Madison Medical School, Madison, WI
1984	NCI Summer Training Award; National Institutes of Health, Bethesda, MD
1993	McDonnell Scholar in Molecular Oncology; Washington University Medical Center, St. Louis, MO
1998	28th Mallinckrodt Scholar, Edward Mallinckrodt, Jr. Foundation
2000	Election to American Society of Clinical Investigation
2005	Medical Advisory Board of the Severe Congenital Neutropenia International Registry
2009	Election to the Association of American Physicians
2009	Alan and Edith Wolff Endowed Professor
2009	Executive committee of the Severe Congenital Neutropenia International Registry
2010	Outstanding Faculty Mentor Award, Washington University
2010	Member, American Society of Hematology Scientific Subcommittee on Myeloid Biology
2011	Distinguished Faculty Award for Graduate Student Teaching, Washington University

Editorial Responsibilities

2002	Editorial Board, Experimental Hematology
2002	Editorial Board, Blood

Professional Societies

	Alpha Omega Alpha
	American Society of Hematology
	American Society of Clinical Investigation
	Association of American Physicians
	International Society for Experimental Hematology

Board Memberships

	Medical Advisory Board of the Severe Congenital Neutropenia International Registry
	Executive Committee of the Severe Congenital Neutropenia International Registry
	External advisory committee NASA Specialized Center on Research in Radiation Carcinogenesis
	External Advisory board, Albert Einstein Cancer Center

• Updated: February 9, 2012
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