Michael F. Clarke
Professor
Medicine - Oncology
Stanford University
United States of America
Biography
Dr. Michael F. Clarke is the Associate Director of the Stanford Institute for Stem Cell and Regenerative Medicine. In addition to his clinical duties in the division of Oncology, Dr. Clarke maintains a laboratory focused on two areas of research: i) the control of self-renewal of normal stem cells and their malignant counterparts; and ii) the identification and characterization of cancer stem cells. A central issue in stem cell biology is to understand the mechanisms that regulate self-renewal of hematopoietic stem cells, which are required for hematopoiesis to persist for the lifetime of the animal. Until recently, the molecular mechanisms that regulate adult stem cell self-renewal were not known. His laboratory recently found that the proto-oncogene Bmi-1 regulates stem cell self-renewal via an epigenetic mechanism. By investigating the pathways upstream and downstream of Bmi1, the laboratory is actively investigating the molecular pathways that regulate self-renewal. Recently his laboratory has found that USP16, a protein that dampens Bmi1 signals, causes a stem cell defect in various stem cells in Down’s syndrome, including neural stem cells.
Research Interest
Dr. ClarkeÂ’s laboratory will provide other members of the program with the expertise to identify and isolate cancer stem cells from solid tumors of epithelial origin. Finally, the laboratory is actively pursuing how cancer stem cells self-renew to maintain themselves and escape the genetic constraints on unlimited self-renewal that regulate normal stem cell numbers. Differences in self-renewal pathways between normal and malignant stem cells could be targeted by new therapeutic agents to eliminate cancer stem cells.
Publications
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Akala OO, Park I, Qian D, Pihalja M, Becker MW, et al. (2008) Long-term haematopoietic reconstitution by Trp53(-/-)p16(Ink4a-/-)p19(Arf-/-) multipotent progenitors. Nature 453: 228-U12
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Shimono Y, Zabala M, Cho RW, Lobo N, Dalerba P, et al. (2009) Downregulation of miRNA-200c Links Breast Cancer Stem Cells with Normal Stem Cells. Cell 138: 592-603.
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Adorno M, Sikandar S, Mitra SS, Kuo A, Nicolis Di Robilant B, et al. (2013) Usp16 contributes to somatic stem-cell defects in Down's syndrome. Nature 501: 380-384.