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

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

    • Professor of Pediatrics School of Medicine
    • Cancer Biology Graduate Program School of Medicine
    • Cell and Developmental Biology Graduate Program School of Medicine
    • Program in Molecular and Cellular Biosciences School of Medicine

Over the past several years, my laboratory has been interested in functional relationship between hematopoiesis and blood vessel formation. Recently, we have found that adult vascular endothelial cells are an important component of the hematopoietic microenvironment. Specifically, endothelial cells can produce signals that protect hematopoietic stem cells (HSCs) from radiation induced cell death. Classical  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. A single HSC can give rise to both hematopoietic and endothelial cells in vivo providing direct evidence for the existence of an adult hemangioblast. Additional studies demonstrate that endothelial cells can arise from hematopoietic progenitors cells committed to the myelomonocytic cell lineages. These functional interactions between HSCs and blood vessels represent a new area of investigation that has important implications for our understanding of both normal and malignant hematopoiesis.

  • Residency:

    • 1987- 89 Stanford University Hospital, Stanford
  • Fellowship:

    • 1989- 93 Stanford University Hospital, Stanford
  • Certifications:

    • Internal medicine, medical oncology

Memberships and associations

  • Internal medicine, 1995

Publications

  • "BMP4 regulates the hematopoietic stem cell niche" Blood November 12 2009
  • "Apoptosis-stimulating protein of p53 (ASPP2) heterozygous mice are tumor-prone and have attenuated cellular damage-response thresholds" Proceedings of the National Academy of Sciences of the United States of America March 17 2009
  • "Impact of donor lymphocyte infusion for hematological malignancy relapsed after allogeneic bone marrow transplantation" Cancer Research, Therapy and Control  1998
  • "Engraftment potential of different sources of human hematopoietic progenitor cells in BNX mice" Blood April 15 1996
  • "Adult blood vessels restore host hematopoiesis following lethal irradiation" Experimental Hematology  2002
  • "Hematopoietic stem cells contribute to lymphatic endothelium" PLoS One November 26 2008
  • "Steel factor influences the distribution and activity of murine hematopoietic stem cells in vivo" Proceedings of the National Academy of Sciences of the United States of America April 15 1993
  • "Corepressor Rcor1 is essential for murine erythropoiesis" Blood May 15 2014
  • "Activation of the G-CSF and Flt-3 receptors protects hematopoietic stem cells from lethal irradiation" Experimental Hematology November 2003
  • "Endothelial cells mitigate DNA damage and promote the regeneration of hematopoietic stem cells after radiation injury" Stem Cell Research  2013
  • "Heterogeneity of hematopoietic stem cells" Current Opinion in Immunology  1993
  • "MHC class II gene silencing in trophoblast cells is caused by inhibition of CIITA expression" American Journal of Reproductive Immunology and Microbiology December 1998
  • "Converging roads" Experimental Hematology November 2003
  • "Intestinal microbiota-derived metabolomic blood plasma markers for prior radiation injury" International Journal of Radiation Oncology Biology Physics  2015
  • "Fancd2-/- mice have hematopoietic defects that can be partially corrected by resveratrol" Blood December 9 2010
  • "HCMV Infection of Humanized Mice after Transplantation of G-CSF-Mobilized Peripheral Blood Stem Cells from HCMV-Seropositive Donors" Biology of Blood and Marrow Transplantation January 2014
  • "Progenipoietin-1A multifunctional agonist of the granulocyte colony-stimulating factor receptor and fetal liver tyrosine kinase-3 is a potent mobilizer of hematopoietic stem cells" Experimental Hematology  2001
  • "CD34+ progenitor cells from asymptomatic patients are not a major reservoir for human immunodeficiency virus-1" Blood  1995
  • "Toxic megacolon" Bone Marrow Transplantation September 2002
  • "Transplanted human bone marrow contributes to vascular endothelium" Proceedings of the National Academy of Sciences of the United States of America November 30 2004
  • "The hereditary hemochromatosis protein, HFE, lowers intracellular iron levels independently of transferrin receptor 1 in TRVb cells" Blood March 15 2005
  • "A novel human cytomegalovirus locus modulates cell type-specific outcomes of infection" PLoS Pathogens December 2011
  • "Functional integration of acute myeloid leukemia into the vascular niche" Leukemia October 1 2014
  • "Endothelial cell-specific markers" Blood August 1 2005
  • "Lymphoid reconstitution after autologous PBSC transplantation with FACS- sorted CD34+ hematopoietic progenitors" Blood April 1 1998
  • "Competitive engraftment of adult and fetal murine hematopoietic progenitor cells following in utero transplantation" Experimental Hematology  1997
  • "Phase I/Ii study of combination high-dose therapy with busulfan, thiotepa, and total body irradiation (TBI) for the treatment of aggressive multiple myeloma" Blood  2000
  • "Mouse models of hematopoietic engraftment" Stem Cells  2006
  • "Sequential versus concurrent administration of daniplestim and g-csf for the mobilization of hematopoietic progenitors in non-human primates" Experimental Hematology  1997
  • "The corepressor Rcor1 is essential for normal myeloerythroid lineage differentiation" Stem Cells November 1 2015

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