Michael F. Clarke, M.D.

Clinical Focus

• Cancer
• Colorectal Cancer
• Oncology
• Oncology (Cancer)

Honors and Awards

• Rackham Award, University of Michigan (-)
• American Society of Clinical Investigation, - (-)
• American Association of Physicians, - (-)

Professional Education

• Residency: Indiana University School of Medicine, IN (1980)
• Internship: University Of Missouri, MO (1978)
• Medical Education: Indiana University School of Medicine, IN (1977)
• M.D., Indiana University, (1977)
• B.A., Indiana University, (1973)

Postdoctoral Advisees

Maddalena Adorno, Piero Dalerba, Huiping Liu, Ferenc Scheeren, Maider Zabala Ugalde

Research Interests

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.

Cancers arise as a result of a series of genetic mutations. A better understanding of the consequences of these mutations on the underlying biology of the neoplastic cells will help to focus the development of more effective therapies. Solid tumors such as breast cancers contain heterogeneous populations of neoplastic cells. Dr. Clarke’s group has developed a technique that allows the isolation and characterization of tumorigenic and non-tumorigenic populations of cancer cells present in human breast, colon and head and neck cancer tumors. Only a small minority of cancer cells had the capacity to form new tumors in a xenograft model. This tumorigenic cell population could be identified prospectively and consistently had definable and identical phenotype. The tumorigenic cells displayed stem cell-like properties in that they were capable of generating new tumors containing additional stem cells as well as regenerating the phenotypically mixed populations of non-tumorigenic cells present in the...

Publications

• The prognostic role of a gene signature from tumorigenic breast-cancer cells. Liu R, Wang X, Chen GY, Dalerba P, Gurney A, Hoey T, Sherlock G, Lewicki J, Shedden K, Clarke MF "N Engl J Med" 2007 ; 3 (356) : 217-26
• Stem cells and cancer: two faces of eve. Clarke MF, Fuller M "Cell" 2006 ; 6 (124) : 1111-5
• Prospective identification of tumorigenic breast cancer cells. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF "Proc Natl Acad Sci U S A" 2003 ; 7 (100) : 3983-8
• Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Park IK, Qian D, Kiel M, Becker MW, Pihalja M, Weissman IL, Morrison SJ, Clarke MF "Nature" 2003 ; 6937 (423) : 302-5
• Stem cells, cancer, and cancer stem cells. Reya T, Morrison SJ, Clarke MF, Weissman IL "Nature" 2001 ; 6859 (414) : 105-11