William H. Fleming M.D., Ph.D.

Associate Professor of Medicine

Biography

1981- 87 M.D., Ph.D., University of Manitoba, Canada
1987- 89 Medical Intern/Resident, Stanford University
1989- 93 Oncology Fellow, Stanford University
1990- 93 Postdoctoral Fellow, Stanford University, (Dr. Irv Weissman)
1993- 97 Assistant Professor of Medicine, Emory University
1997- 01 Assistant Professor of Medicine, Oregon Health & Sciences University
2001- Associate Professor of Medicine, Oregon Health & Sciences University

Research Interests

Over the past few years, my laboratory has been interested in determining if the close functional relationship between hematopoiesis and blood vessel formation characteristic of embryonic development persists into adult life. Recently, we have found that adult vascular endothelial cells produce factors or signals that protect hematopoietic stem cells (HSC) from radiation induced cell death. Classic studies in embryology demonstrated the existence of the hemangioblast, a stem cell that can give rise to both hematopoiesis and blood vessels. To address the question of whether bone marrow derived cells with hemangioblast activity exist in the adult, the vascular compartment of bone marrow transplanted mice and humans was carefully evaluated for the presence of donor derived cells. A similar frequency of bone marrow derived endothelial cells was detected in both mouse and human transplant recipients. In the mouse model, transplantation of a single HSC gave rise to both hematopoietic and endothelial cell outcomes providing evidence for the existence of an adult hemangioblast. The functional interactions between HSC and blood vessels represent a new area of investigation that may have important implications for our understanding of hematopoietic and vascular disease. Ongoing studies are focused on determining the mechanisms responsible for both steady state homeostasis and injury induced, tissue regeneration.

Selected references

Anderson DA, Wu Y, Shuguang J, Zhang X, Streeter PR, Spangrude GD, Archer DR, Fleming,WH: Donor marker infidelity in transgenic hematopoietic stem cells. Stem Cells (2005, In Press)

Jiang S, Walker L, Afentoulis M, Anderson DA, Jauron-Mills, L, Corless CL, Fleming, WH: Transplanted human bone marrow contributes to vascular endothelium. Proc Natl Acad Sci U S A. 101:16891-16896, 2004.

Baumann CI, Bailey AS, Li W, Ferkowicz MJ, Yoder MC, Fleming WH: PECAM-1 is expressed on hematopoietic stem cells throughout ontogeny and identifies a population of erythroid progenitors. Blood. 104:1010-1016, 2004.

Willenbring H, Bailey AS, Foster M, Akkari Y, Dorrell C, Olson S, Finegold M, Fleming WH, Grompe M: Myelomoncytic cells are sufficient for therapeutic cell fusion in liver. Nature Med. 10:744-748, 2004.

Bailey AS, Jiang S, Afentoulis M, Baumann CI, Schroeder DA, Olson SB, Wong, MH, Fleming WH: Transplanted adult hematopoietic stems cells differentiate into functional endothelial cells. Blood. 103:13-19, 2004.

Bailey AS, Fleming WH: Converging Roads: Evidence for an adult hemangioblast. Exp Hematol. 31:987-993, 2003.

Montfort MJ, Olivares CR, Mulcahy JM, Fleming WH: Adult blood vessels restore host hematopoiesis following lethal irradiation. Exp. Hematol. 30:950-956, 2002