Hal E. Broxmeyer, Ph.D.
Professor of Microbiology/Immunology
Co-Leader, Program on Hematopoiesis, Malignant Hematology, and Immunology, Indiana University Simon Cancer Center
Summary of the focus of the research of Dr. Broxmeyer
The laboratory focuses on mechanisms regulating proliferation, survival, self-renewal, metabolism, differentiation and homing/mobilization of hematopoietic, embryonic, and induced pluripotent stem cells at cellular, intracellular, and animal levels, as well as gene transfer, to influence these functions.
Description and summary of research focus of the laboratory
Dr. Broxmeyer's laboratory is interested in blood cell production (hematopoiesis) in the context of normal and abnormal cell regulation as assessed in vitro and in vivo. 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/chemokines for treatment of hematological disorders. His laboratory has been involved in studies assessing and establishing the use of cord blood for transplantation, and in vivo effects of cytokines, especially in patients on clinical trial. His laboratory demonstrated that inactivation/deletion of the peptidase activity of CD26/Dipeptidylpeptidase (DPP) IV on murine and human stem cells greatly enhances their homing and engraftment capability and clinical trials are ongoing to use this to enhance engraftment of cord blood cells, and that DPPIV can truncate and change the activity of a number of growth regulating factors. They have demonstrated the potent stem and progenitor cell mobilizing capacity of AMD3100, an antagonist of SDF-1/CXCL12 binding to its receptor CXCR4, that led the clinical trials with AMD3100 in this context. Most recently they demonstrated that removal of hematopoietic stem cells under ambient air as everyone does acts as a strong stress that immediately differentiates them and this greatly reduces their numbers, and that reduction of this stress results in greatly enhanced recovery of numbers of transplantable stem cells. They have also found new means to ex-vivo expand hematopoietic stem cells, and to enhance their homing and engrafting capabilities. The laboratory also studies maintenance and hematopoietic differentiation of embryonic and induced pluripotent stem cells. Intracellular signal transduction studies are utilized to evaluate mechanisms of cell proliferation and survival, mobilization of cells from the marrow to the blood, and homing from blood to marrow. This includes viral-gene transfer approaches. Mice in which specific genes are either deleted or inserted are utilized to determine dominant regulatory effector proteins. Recent studies have focused on: metabolism and mitochondria.
- Broxmeyer, H.E., Hoggatt, J., O’Leary, H.A., Mantel, C., Chitteti, B.R., Cooper, S., Messina-Graham, S., Hangoc, G., Farag, S., Rohrabaugh, S.L., Ou, X., Speth, J., Pelus, L.M., Srour, E.F., Campbell, T.B. 2012. Dipeptidylpeptidase 4 Negatively Regulates Colony Stimulating Factor Activity and Stress Hematopoiesis. Nature Medicine. 18:1786-1796. PMCID:PMC3742313
- Lee, M.R., Prasain, N., Chae, H-D., Kim, Y.J., Mantel, C., Yoder, M.C., and Broxmeyer, H.E. 2013. Epigenetic regulation of Nanog by miR-302 cluster-MBD2 completes induced pluripotent stem cell reprogramming. Stem Cells. 31:666-681. PMCID: PMC3904370
- Ou, X., Lee, M-R., Huang, X.X., Messina-Graham, S., and Broxmeyer, H.E. 2014. Sirt1 positively regulates autophagy and mitochondria function in embryonic stem cells under oxidative stress. Stem Cells. 32(5):1183-1194. PMCID: PMC3991763
- Mantel, C.R., O’Leary, H.A. Chitteti, B.R., Huang, X., Cooper, S., Hangoc, G., Brustovetsky, N., Srour, E.F., Lee, M.R., Messina-Graham, S., Haas, D.M., Falah, N., Kapur, R., Pelus, L.M., Bardeesy, N., Fitament, J., Ivan, M., Kim, K-S., and Broxmeyer, H.E. 2015. Enhancing hematopoietic stem cell transplantation efficacy by mitigating oxygen shock. Cell. 161:1553-1565. PMC4480616 [Available on 2016-06-18]
- Capitano, M.L., Hangoc, G., Cooper, S., and Broxmeyer, H.E. 2015. Mild heat treatment primes human CD34+ cord blood cells for migration towards SDF-1a and enhances engraftment in an NSG mouse model. Stem Cells. 33(6):1975-1984. PMC4441568 [Available on 2016-06-01]
- Huang, X., Lee, M.R., Cooper, S., Hangoc, G., Hong, K-S., Chung, H-M., and Broxmeyer, H.E. 2015. Activation of OCT4 enhances ex vivo expansion of human cord blood hematopoietic stem and progenitor cells by regulating HOXB4 expression. Leukemia. 2015 Jul 23. doi: 10.1038/leu.2015.189. [Epub ahead of print]
- B.Sc., 1966: Brooklyn College, City University of New York
- M.Sc., 1969: Long Island University, Brooklyn Campus
- Ph.D., 1973: New York University
- Post Doctoral: 1973-1975: Queens University, Kingston, Ontario
- Distinguished Professor, 2004 - present: Indiana University School of Medicine, Indianapolis, IN
- Professor of Microbiology and Immunology, 1997-Present: Indiana University School of Medicine, Indianapolis, IN
- Mary Margaret Professor Emeritus, 2010-Present: Indiana University School of Medicine, Indianapolis, IN
- Chairman of Microbiology and Immunology, 1997-2010: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN
- Scientific Director, 1988-2009: 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, 1997-2009: 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