Michael Y. Sherman
Professor of Biochemistry
Department of Biochemistry
Boston University School of Medicine
Silvio Conte Building
72 E. Concord Street
Boston, MA 02118
Phone: (617) 638-5971
Fax: (617) 638-5339
Email: sherma1@bu.edu
Education
Ph.D., Moscow University, Russia
Research Interests
Research in my lab has focused on understanding the molecular mechanisms underlying the central role of the heat shock protein Hsp72 in cancer. It has been known for years that in cancer cells Hsp72 is often expressed at very high levels, and its expression correlates with the aggressiveness of tumors. Recently we have found that Hsp72 regulates early stages of tumorigenesis. Indeed, Hsp72 can control signaling pathways initiated by major oncogenes, resulting in avoiding growth inhibition and facilitating cell proliferation and transformation.
Our current research within this project addresses several questions:
- How Hsp72 keeps the p53 pathway activated by PIK3CA oncogene under control?
- How Hsp72 prevents cell senescence activated by Ras and Her2 oncogenes.
In this work we utilize a combination of biochemical and genetic approaches using cell culture and transgenic mice.
In a distinct project we study a process of aggregation of abnormal polypeptides. When chaperone and protein degradation machineries fail to handle abnormal proteins, they aggregate and cause cell toxicity, which may give rise to various neurological disorders. As the last line of defense, a special machinery has evolved that transports these toxic aggregates to a centrosome location via microtubules, which leads to relieve of toxicity. The resulting non-toxic single large aggregate is called aggresome. Previously we have established a yeast model to study aggregation and toxicity of the disease-causing polypeptides with expanded polyglutamine domain. Now, using both yeast and mammalian systems, we are dissecting the pathway of aggresome formation.
Our current research within this project uses genetics and biochemical approaches to addresses the following questions:
- What cellular components are involved in aggresome formation?
- What signaling pathways control aggresome formation?
- Are there common cellular pathways of aggregation of polypeptides involved in various types of neurological disorders?
Click here for Research Faculty in the Sherman Lab
Selected Recent Publications
1. Ganusova E.E., Ozolins L.N., Bhagat S., Newnam G.P., Wegrzyn R.D., Sherman M.Y., Chernoff Y.O. Modulation of prion formation, aggregation, and toxicity by the actin cytoskeleton in yeast. (2006) Mol. Cell. Biol. 26:617-629.
2. Zaarur N., Gabai V.L., Porco J., Calderwood S., Sherman M.Y. Novel blockers of the Heat Shock Response sensitize cancer cells to proteasome and Hsp90 inhibitors. (2006) Cancer Research, 66: 1783-1791.
3. Sherman M.Y., Gabai V.L. Multiple thermometers in mammalian cells: why do cells from homeothermic organisms need to measure temperature? (2006) Science STKE, 328:pe16.
4. O’Callaghan-Sunol C., Sherman M.Y. Heat shock transcription factor (HSF1) plays a critical role in cell migration via maintaining MAP kinase signaling. (2006) Cell Cycle 5:13, 1431-7.
5. Calderwood S.K., Ciocca D.R., Zaarur N., Lepchammer S. and Sherman M.Y. The Elevated Levels of Heat Shock Proteins In Cancer: A Suitable Case For Treatment? In Heat Shock Proteins in Cancer. (2007) S. Calderwood, M.Y. Sherman, D. Ciocca ed. Cambridge Press.
6. Sherman M.Y. and Yaglom J. Role of molecular chaperones in cell senescence. In Heat Shock Proteins in Cancer. (2007) S. Calderwood, M.Y. Sherman, D. Ciocca ed. Cambridge Press.
7. Meriin A.B., Zhang X.-Q., Chernoff Y.O., Sherman M.Y. Aggregation of proteins with polyglutamine domains requires endocytosis machinery. (2007) FASEB J., 21:1915-25.
8. Yaglom J., Gabai V.L., Sherman, M.Y. High levels of heat shock protein Hsp72 in cancer cells suppress default senescence pathways. (2007) Cancer Research, 67:2373-81.
9. Sherman M.Y. Gabai V.L., O’Callaghan C. and Yaglom J. Molecular chaperones regulate p53 and suppress senescence programs. Invited review. (2007) FEBS Lett., 581:3711-3715.
10. Wang Y., Meriin M.B., Costello C., Sherman M.Y. Characterization of proteins associated with polyglutamine aggregates: a novel approach towards isolation of aggregates from protein conformation disorders. (2007) Prion, 1:128-135.
11. Sherman M.Y., Multhoff G. Heat shock proteins in cancer. (2007) Ann. N.Y. Acad. Sci. 1113: 192–201.
12. O’Callaghan-Sunol C., Gabai V.L., Sherman M.Y. Hsp27 modulates p53 signaling and suppresses cellular senescence. (2007) Cancer Research, 67:11779-88.
