Michael Y. Sherman

shermanProfessor

Boston University School of Medicine
Silvio Conte Building
72 E. Concord Street
Boston, MA 02118

Phone: (617) 638-5971
Lab Phone: (617)638-5970
Fax: (617) 638-5339
Email: sherma1@bu.edu

Education

PhD, Moscow University, Russia

People

Vladimir Gabai
Research Asst. Professor		 Julia Yaglom
Research Asst. Professor		 Le Meng
Student
Anatoli Meriin
Research Asst. Professor		 Nava Zaarur
Postdoctoral Fellow		 Terri Mills
Student
Geunwon Kim
Student

Research Interests

I. Research in my lab has focused on understanding the molecular mechanisms underlying the central role of the heat shock protein Hsp72 in cancer. 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 research addresses several questions:

(1) How Hsp72 keeps the p53 pathway activated by PIK3CA oncogene under control?

(2) How Hsp72 prevents cell senescence activated by Her2 oncogene.

II. 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:

(1) What cellular components are involved in aggresome formation?

(2) What signaling pathways control aggresome formation?

Research Themes

Neuroscience & Aging; Signal Transduction & Cancer

Representative Publications

  • Gabai V.L., Yaglom J.A., Waldman T. and Sherman M.Y. Heat shock protein Hsp72 controls oncogene-induced senescence pathways in cancer cells. (2009) Mol.Cell.Biol., 29:559-569.
  • Wang Y., Meriin A.B., Zaarur N., Romanova N.V., Chernoff Y.O.,E. Castello C., Sherman M.Y. Aggresome in yeast: Aggresome-targeting signal and components of the machinery. FASEB J. 2009 23:451-63.
  • Zaarur N., Meriin A.B., Gabai V.L. and Sherman M.Y. Triggering aggresome formation: Aggregation and aggresome-targeting signals in Synphilin 1. (2008) J.Biol.Chem., 283:27575-84.
  • Ilyinskii P.O., Thoidis G., Sherman M.Y., Shneider A. Adjuvant potential of aggregate-forming polyglutamine domains. (2008) Vaccine, 26:3223-6.
  • Park M.A., Yacoub A., Rahmani M., Zhang G., Hart L., Hagan M.P., Calderwood S.K., Sherman M.Y., Koumenis C., Spiegel  S., Chen C.S., Graf M., Curiel D.T., Fisher P.B., Grant S., and Dent P. OSU-03012 stimulates PERK-dependent increases in HSP70 expression that act to attenuate its lethal actions in transformed cells. (2008) Molecular Pharmacology, 73:1168-84.
  • Gabai V.L., O’Callaghan-Sunol C., Meng L., Sherman M.Y., Yaglom J. Activation of cellular senescence programs leads to suppression of the protein kinase Chk1 and enhances sensitivity to genotoxic stresses. (2008) Cancer Research, 68:1834-42.
  • O’Callaghan-Sunol C., Gabai V.L., Sherman M.Y. Hsp27 modulates p53 signaling and suppresses cellular senescence. (2007) Cancer Research, 67:11779-88.
  • Sherman M.Y., Multhoff G. Heat shock proteins in cancer. (2007) Ann. N.Y. Acad. Sci. 1113: 192–201.
  • 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.
  • Sherman M.Y. Universal Genome in the Origin of Metazoa: Thoughts about Evolution. (2007) Cell Cycle, 6:1873-1877.
  • 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.
  • 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.
  • 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.