Michael F. Clarke, M.D.
Professor,
Department of Internal Medicine
& Cell & Developmental Biology
mclarke@umich.edu

This laboratory is interested in two areas: i) the genetic control of self-renewal of normal hematopoietic stem cells; and ii) the identification and characterization of cancer stem cells. 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.

Our lab has developed a technique that allows the isolation and characterization of tumorigenic and non-tumorigenic populations of cancer cells present in human breast 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 original tumor. The expression of potential therapeutic targets differed between the tumorigenic and non-tumorigenic populations.Effective treatment of breast cancer will require therapeutic strategies that are able to target and eliminate this tumorigenic subset of cells.

Representative publications:

Weber, B.L., Westin, E. and Clarke, M.F.: Differentiation of mouse erythroleukemia cells enhanced by alternatively spliced c-myb mRNA. Science, 249:1291-1293, 1990.

Park, I, Klug, C., Kaijun, L., Jerabek, L., Linheng, Li, Nanamori, M., Neubig, R.R., Hood, L., Weissman, I.L., Clarke, M.F.. Molecular Cloning and Characterization of a Novel Regulator of G-Protein Signaling from Mouse Hematopoietic stem Cells. J. Biol. Chem. 276:2(915-928) 2001.

Reya T., Morrison SJ., Clarke MF., Weissman IL. Stem Cells, Cancer and Cancer cells. Nature 414:105-111, 2001.

Al-Hajj, M., Wicha, M, Morrison, S.J., Clarke, M.F. Prospective identification and characterization of a tumorigenic breast cancer cell. PNAS100: 3983-3988, 2003.

Park, I, Kiel, M, Morrisson, S, Weissman, IL, and Clarke, M.F. Bmi1 is required for adult hematopoietic stem cell self renewal. Nature 423. 302-305, 2003