Training
• B.Sc., 1966: Brooklyn College, City University of New York
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M.Sc., 1969: Long Island University, Brooklyn Campus
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Ph.D., 1973: New York University
• Post Doctoral: 1973-1975: Queens University, Kingston, Ontario Positions
Distinguished Professor, 2004 - present: Indiana University School of Medicine, Indianapolis, IN Chairman, 1997-present: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN Scientific Director, 1988-present: Walther Oncology Center, Indiana University School of Medicine, Indianapolis, IN Mary Margaret Walther Professor of Medicine, 1989-1997: Indiana University School of Medicine, Indianapolis, IN Mary Margaret Walther Professor of Microbiology/Immunology, 1997-present: Indiana University School of Medicine, Indianapolis, IN Professor of Medicine and Microbiology/Immunology, 1986-1997: Indiana University School of Medicine Director of Cancer Research of the Regenstrief Foundation, 1983-1987: Indiana University School of Medicine, Indianapolis, IN Associate Professor of Medicine and Microbiology / Immunology, 1983-1986: Indiana University School of Medicine, Indianapolis, IN Assistant Professor of Biology, 1980- 1983: Sloan Kettering Division, Cornell University Graduate School of Medical Sciences. Associate Member, 1983: Sloan Kettering Institute for Cancer Research, New York Associate, 1978-1983: Sloan Kettering Institute for Cancer Research, New York Research Associate/Associate Researcher, 1975-1978: Sloan Kettering Institute for Cancer Research, New York Summary of the focus of the research of Dr. Broxmeyer
The laboratory focuses on mechanisms regulating the growth, survival and homing/mobilization of hematopoietic stem and progenitor cells at cellular, intracellular, and animal levels, as well as gene transfer, gene therapy to influence these functions. It also focuses on immune activity and differentiation of T-lymphocytes, monocytes, and dendritic cells.
Description and summary of research focus of the laboratory:
Dr. Broxmeyer's laboratory is interested in the study of blood cell production (hematopoiesis) in the context of normal and abnormal cell regulation as assessed in vitro and in vivo at the level of proliferation/self-renewal/differentiation/apoptosis and homing/migration of hematopoietic stem and progenitor cells and also of the immunology of cord blood and adult immune cells. This latter interest in cord blood immune cells dates back to his pioneering work in helping to establish the field of cord blood transplantation, and the clinical finding that cord blood transplantation elicits a lowered level of graft vs host disease, but normal level of graft vs leukemia effect compared to bone marrow transplantation. As a clinical correlate, his laboratory is interested in the use of hematopoietic stem and progenitor cells, especially those from umbilical cord blood, for transplantation purposes, and the use of cytokines for treatment of hematological disorders. Over the years the laboratory has been involved in many studies assessing the in vivo effects of cytokines, especially in patients on clinical trial. His group has focused recently on the family of molecules called chemokines for enhancement of proliferation, survival, or movement (homing and mobilization) of early subsets of blood cells, alone and in the presence of colony stimulating factors and the potent co-stimulating ligands, stem cell factor and Flt3-ligand for tyrosine kinase receptors. His laboratory recently demonstrated that inactivation/deletion of the peptidase activity of CD26 on murine stem cells greatly enhances their homing and engraftment capability, and studies on human cells are ongoing as a prelude to clinical translation efforts. They have also done studies with the SDF-1/CXCL12-CXCR4 antagonist AMD3100, that helped demonstrate the potent stem and progenitor cell mobilizing capacity of AMD3100 that led the clinical trials with AMD3100 in this context. The laboratory also studies the growth and hematopoietic differentiation of murine embryonic stem cells. Intracellular signal transduction studies are utilized to evaluate the mechanisms of cell proliferation and survival, mobilization of cells from the marrow to the blood and chemotaxis. This includes gene transfer, gene therapy approaches. Mice in which specific genes are either deleted or inserted are utilized to determine dominant regulatory effector proteins. Recent studies have focused on mice in which the following genes involved in intracellular signaling have been "knocked-out": p21cip1, p18INK4C, p27kip1, p18/p27, p18/p21, SHIP, SHP-1, Stat4, Stat6, Stat 5a, Stat 5b, CIITA, BCL-6 and BAZF. Studies with CD1d deleted mice are also ongoing as are those with Stat-3 deletions and IL-31 receptor deletions. His group has also focused on transgenic mice expressing the chemokine SDF-1/CXCL12. Studies are ongoing in the area of the immune reactivity of cord blood vs. adult T lymphocytes, monocytes and dendritic cells, and the differentiation of these cells.
Publications
Christopherson, K.W. II, Hangoc, G., Mantel, C., and Broxmeyer, H.E. 2004. Modulation of hematopoietic stem cell homing and engraftment by CD26. Science. 305:1000-1003.
Kim, Y-J., Stringfield, T.M., Chen, Y., and Broxmeyer, H.E. 2005. Modulation of cord blood CD8 + T cell effector differentiation by TGF- β 1 and 4-1BB costimulation. Blood. 105:274-281.
Li, G., Kim, Y.J., and Broxmeyer, H.E. 2005. Macrophage colony-stimulating factor drives cord blood monocyte differentiation into IL-10 highIL-12 absent dendritic cells with tolerogenic potential. J. Immunol. 174:4706-4717.
Broxmeyer, H.E. , Orschell, C.M., Clapp, D.W., Hangoc, G., Cooper, S., Plett, A., Liles, W.C., Li, X., Graham-Evans, B., Campbell , T.B., Calandra, G., Bridger, G., Dale , D.C. , and Srour, E.F. 2005. Rapid mobilization of murine and human hematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist. J. Exp. Med. 201:1307-1318.
Basu, S., and Broxmeyer, H.E. 2005. Transforming growth factor- β 1 modulates responses of CD34+ cord blood cells to stromal cell derived factor-1/CXCL12. Blood. 106:485-493.
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