Edward F. Srour, Ph.D.
Robert J. and Annie S. Rohn Professor of Leukemia Research
Professor of Medicine
Professor of Pediatrics
Professor of Microbiology & Immunology
Director of Flow Cytometry Resource Facility
Summary of the focus of research
Stem cell biology including cells of hematopoietic origin and candidate adult pluripotent stem cells from other tissues as well as cancer stem cells with special focus on stem cells in multiple myeloma.
Description and summary of research focus of the laboratory
Research in Dr. Srour’s laboratory has focused on the characterization and biology of human and murine hematopoietic stem cells (HSC), their use in bone marrow transplantation, and how stem cell fate determination is impacted by exogenous factors. Successful transplantation and engraftment of HSC are dependent on the cell cycle status of transplanted stem cells and their ability to home to the bone marrow of mice receiving these cells, and on the competence of the hematopoietic niche in supporting the survival and proliferation of HSC. Therefore, studies in the Srour laboratory are aimed at understanding how these parameters, individually, and collectively, impact selfrenewal, proliferation, differentiation, and fate of HSC.
1) Examination of the relationship between cell cycle status of primitive hematopoietic progenitor cells and its effect on engraftment and maintenance of bone marrow repopulating potential. Our laboratory documented that following transplantation, HSC remain quiescent in the bone marrow for a long period of time. The reasons behind this delayed cell cycle activation is not known but is believed to be a protective measure HSC undertake in a hostile microenvironment. Using a murine model of transplantation, the laboratory is examining cell cycle regulation in marrow homed cells after they anchor to either the endothelial or the endosteal regions of the marrow microenvironment.
2) In a collaborative effort, the Srour laboratory is trying to define how different cellular and matrix elements of the hematopoietic microenvironment control stem cell maintenance through self-renewal divisions and differentiation and ultimately the size of the stem cell pool. Because of their importance in the architecture of the hematopoietic niche, these studies examine in detail the nature of osteoblasts with which HSC interact in the niche and try to identify the hierarchical arrangement of osteoblastic progenitors in this lineage. The laboratory described recently a unique interaction between osteoblasts and adipocytes whereby the latter suppresses the hematopoiesis enhancing activity promoted by the former. Therefore efforts are now underway to characterize the molecular pathways involved in these antagonizing effects of osteoblasts and adipocytes in the hematopoietic niche.
3) Multiple myeloma (MM) represents a unique cancer in which cancer stem cells reside in the bone marrow, and most likely interact intimately with osteoblasts present in the hematopoietic microenvironment. In a collaborative effort, the laboratory is examining the role of a new marker in the pathobiology of MM and the bone loss associated with this disease, and in investigating whether targeting this molecule will inhibit MM cells both in vitro and in vivo using a murine model of the disease.
- Broxmeyer HE, Orschell CM, Clapp DW, Hangoc G, Cooper S, Plett PA, Liles WC, Li X, Graham-Evans B, Calandra G, Bridger G, Dale DC, Srour EF. Rapid mobilization of murine and human hematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist.J. Experimental Medicine 201(8):1307-1318, 2005. (PMCID: PMC2213145)
- Srour, EF, Tong X, Sung KW, Plett AP, Rice S, Daggy J, Yiannoutsos CT, Abonour R, Orschell CM. Modulation of in vitro proliferation kinetics and primitive hematopoietic potential of individual CD34+CD38-/lo cells in G0. Blood 105(8):3109-3116, 2005. (PMID: 15613542)
- Hall K, Horvath TL, Abonour R, Cornetta K, Srour EF. Decreased homing of retrovirally transduced human bone marrow CD34+ cells in the NOD/SCID mouse model. Experimental Hematology 34(4):433-442, 2006. (PMID: 16569590)
- Chitteti BR, Cheng Y-H, Poteat B, Rodriguez-Rodriguez S, Goebel WS, Carlesso N, Kacena MA, Srour EF. Impact of interactions of cellular components of the bone marrow microenvironment on hematopoietic stem and progenitor cell function. Blood 115(16):3239-3248, 2010. (PMCID: PMC2858485)
- Chitteti BR, Cheng Y-H, Streicher DA, Rodriguez-Rodriguez S, Carlesso N, Srour EF, Kacena MA. Osteoblast lineage cells expressing high levels of Runx2 enhance hematopoietic progenitor cell proliferation and function. Journal of Cellular Biochemistry. 111(2):284-294, 2010. (PMID: 20506198)
- Cheng Y-H, Chitteti BR, Streicher DA, Morgan JA, Rodriguez-Rodriguez S, Carlesso N, Srour EF, Kacena MA. Impact of osteoblast maturational status on their ability to enhance the hematopoietic function of stem and progenitor cells.. Journal of Bone Mineral Research. 2011, 26(5):1111-1121 (PMID: 21542011)
- Rodriguez S, Wang L, Mumaw C, Srour EF, Celso CL, Nakayama K, Carlesso, N. The SKP2 E3 Ligase regulates basal homeostasis and stress-induced regeneration of hematopoietic stem cells. Blood 117(24):6509-6519, 2011. (PMCID: PMC3123021)
- Chitteti, BR, Liu Y, Srour EF. Genomic and proteomic analysis of the impact of mitotic quiescence on the engraftment of human CD34+ cells. PLoS One. Mar 7:6(3):e17498, 2011. (PMID:21408179).
- B.Sc., 1979: American University of Beirut, Beirut, Lebanon
- Ingenieur Agricole., 1979: American University of Beirut, Beirut, Lebanon
- M.Sc., 1981: American University of Beirut, Beirut, Lebanon
- Ph.D., 1986: University of Illinois, Urbana-Champaign, IL
- Post Doctoral, 1986-1989: Indiana University