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.
|1981||B.S., University of Wisconsin-Milwaukee, Milwaukee, WI|
|1985||M.D., University of Wisconsin-Madison, Madison, WI|
|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|
|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|
|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|
|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|
|2002||Editorial Board, Experimental Hematology|
|2002||Editorial Board, Blood|
|Alpha Omega Alpha|
|American Society of Hematology|
|American Society of Clinical Investigation|
|Association of American Physicians|
|International Society for Experimental Hematology|
|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|