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

  • "The corepressor Rcor1 is essential for normal myeloerythroid lineage differentiation." Stem Cells In: , Vol. 33, No. 11, 01.11.2015, p. 3304-3314.
  • "The triterpenoid RTA 408 is a robust mitigator of hematopoietic acute radiation syndrome in mice." Radiation Research In: , Vol. 183, No. 3, 01.03.2015, p. 338-344.
  • "Intestinal microbiota-derived metabolomic blood plasma markers for prior radiation injury." International Journal of Radiation Oncology Biology Physics  In: , Vol. 91, No. 2, 2015, p. 360-367.
  • "Functional integration of acute myeloid leukemia into the vascular niche." Leukemia In: , Vol. 28, No. 10, 01.10.2014, p. 1978-1987.
  • "Corepressor Rcor1 is essential for murine erythropoiesis." Blood  In: , Vol. 123, No. 20, 15.05.2014, p. 3175-3184.
  • "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 In: , Vol. 20, No. 1, 01.2014, p. 132-135.
  • "Kinase pathway dependence in primary human leukemias determined by rapid inhibitor screening." Cancer Research In: , Vol. 73, No. 1, 01.01.2013, p. 285-296.
  • "Endothelial cells mitigate DNA damage and promote the regeneration of hematopoietic stem cells after radiation injury." Stem Cell Research In: , Vol. 11, No. 3, 2013, p. 1013-1021.
  • "Multiplex high-throughput gene mutation analysis in acute myeloid leukemia." Human Pathology  In: , Vol. 43, No. 12, 12.2012, p. 2167-2176.
  • "A novel human cytomegalovirus locus modulates cell type-specific outcomes of infection." PLoS Pathogens  In: , Vol. 7, No. 12, e1002444, 12.2011.
  • "Fancd2-/- mice have hematopoietic defects that can be partially corrected by resveratrol." Blood  In: , Vol. 116, No. 24, 09.12.2010, p. 5140-5148.
  • "Granulocyte-colony stimulating factor reactivates human cytomegalovirus in a latently infected humanized mouse model." Cell Host and Microbe In: , Vol. 8, No. 3, 16.09.2010, p. 284-291.
  • "Endothelial cells mediate the regeneration of hematopoietic stem cells." Stem Cell Research In: , Vol. 4, No. 1, 01.2010, p. 17-24.
  • "BMP4 regulates the hematopoietic stem cell niche." Blood In: , Vol. 114, No. 20, 12.11.2009, p. 4393-4401.
  • "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 In: , Vol. 106, No. 11, 17.03.2009, p. 4390-4395.
  • "Hematopoietic stem cells contribute to lymphatic endothelium." PLoS One In: , Vol. 3, No. 11, e3812, 26.11.2008.
  • "Transvection mediated by the translocated cyclin D1 locus in mantle cell lymphoma." Journal of Experimental Medicine  In: , Vol. 205, No. 8, 04.08.2008, p. 1843-1858.
  • "Myeloid lineage progenitors give rise to vascular endothelium." Proceedings of the National Academy of Sciences of the United States of America In: , Vol. 103, No. 35, 29.08.2006, p. 13156-13161.
  • "Bone marrow-derived cells fuse with normal and transformed intestinal stem cells." Proceedings of the National Academy of Sciences of the United States of America In: , Vol. 103, No. 16, 18.04.2006, p. 6321-6325.
  • "In vivo genetic selection of renal proximal tubules." Molecular Therapy  In: , Vol. 13, No. 1, 01.2006, p. 49-58.
  • "Mouse models of hematopoietic engraftment : Limitations of transgenic green fluorescent protein strains and a high-performance liquid chromatography approach to analysis of erythroid chimerism." Stem Cells In: , Vol. 24, No. 9, 2006, p. 2045-2051.
  • "Endothelial cell-specific markers : Going . . . going . . . gone." Blood In: , Vol. 106, No. 3, 01.08.2005, p. 769.
  • "Donor marker infidelity in transgenic hematopoietic stem cells." Stem Cells In: , Vol. 23, No. 5, 05.2005, p. 638-643.
  • "The hereditary hemochromatosis protein, HFE, lowers intracellular iron levels independently of transferrin receptor 1 in TRVb cells." Blood In: , Vol. 105, No. 6, 15.03.2005, p. 2564-2570.
  • "Transplanted human bone marrow contributes to vascular endothelium." Proceedings of the National Academy of Sciences of the United States of America In: , Vol. 101, No. 48, 30.11.2004, p. 16891-16896.
  • "PECAM-1 is expressed on hematopoietic stem cells throughout ontogeny and identifies a population of erythroid progenitors." Blood In: , Vol. 104, No. 4, 15.08.2004, p. 1010-1016.
  • "Myelomonocytic cells are sufficient for therapeutic cell fusion in liver." Nature Medicine  In: , Vol. 10, No. 7, 07.2004, p. 744-748.
  • "Transplanted adult hematopoietic stems cells differentiate into functional endothelial cells." Blood In: , Vol. 103, No. 1, 01.01.2004, p. 13-19.
  • "Activation of the G-CSF and Flt-3 receptors protects hematopoietic stem cells from lethal irradiation." Experimental Hematology In: , Vol. 31, No. 11, 11.2003, p. 1119-1125.
  • "Converging roads : Evidence for an adult hemangioblast." Experimental Hematology In: , Vol. 31, No. 11, 11.2003, p. 987-993.

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