Michael Y. Sherman
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
PhD, Moscow University, Russia
Research Asst. Professor
| Julia Yaglom
Research Asst. Professor
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?
- Hsp70-bag3 interactions regulate cancer-related signaling networks. Colvin TA, Gabai VL, Gong J, Calderwood SK, Li H, Gummuluru S, Matchuk ON, Smirnova SG, Orlova NV, Zamulaeva IA, Garcia-Marcos M, Li X, Young ZT, Rauch JN, Gestwicki JE, Takayama S, Sherman MY. Cancer Res. 2014 Sep 1;74(17):4731-40.
- Proteotoxicity is not the reason for the dependence of cancer cells on the major chaperone Hsp70. Colvin TA, Gabai VL, Sherman MY. Cell Cycle. 2014 Jun 9;13(14).
- Proteasome failure promotes positioning of lysosomes around the aggresome via local block of microtubule-dependent transport. Zaarur N, Meriin AB, Bejarano E, Xu X, Gabai VL, Cuervo AM, Sherman MY. Mol Cell Biol. 2014 Apr;34(7):1336-48.
- Less is more: improving proteostasis by translation slow down. Sherman MY, Qian SB. Trends Biochem Sci. 2013 Dec;38(12):585-91.
- ΔNp63α regulates Erk signaling via MKP3 to inhibit cancer metastasis. Bergholz J, Zhang Y, Wu J, Meng L, Walsh EM, Rai A, Sherman MY, Jim Xiao ZX. Oncogene. 2012 Dec 17. doi: 10.1038/onc.2012.564. [Epub ahead of print]
- Molecular determinants of selective clearance of protein inclusions by autophagy. Wong E, Bejarano E, Rakshit M, Lee K, Hanson HH, Zaarur N, Phillips GR, Sherman MY, Cuervo AM. Nat Commun. 2012;3:1240.
- A novel approach to recovery of function of mutant proteins by slowing down translation. Meriin AB, Mense M, Colbert JD, Liang F, Bihler H, Zaarur N, Rock KL, Sherman MY. J Biol Chem. 2012 Oct 5;287(41):34264-72. doi: 10.1074/jbc.M112.397307. Epub 2012 Aug 17.
- Polyglutamine toxicity is controlled by prion composition and gene dosage in yeast. Gong H, Romanova NV, Allen KD, Chandramowlishwaran P, Gokhale K, Newnam GP, Mieczkowski P, Sherman MY, Chernoff YO. PLoS Genet. 2012;8(4):e1002634. doi: 10.1371/journal.pgen.1002634. Epub 2012 Apr 19.
- The heat shock transcription factor Hsf1 is downregulated in DNA damage-associated senescence, contributing to the maintenance of senescence phenotype. Kim G, Meriin AB, Gabai VL, Christians E, Benjamin I, Wilson A, Wolozin B, Sherman MY. Aging Cell. 2012 Aug;11(4):617-27. doi: 10.1111/j.1474-9726.2012.00827.x. Epub 2012 May 22.
- Association of translation factor eEF1A with defective ribosomal products generates a signal for aggresome formation. Meriin AB, Zaarur N, Sherman MY. J Cell Sci. 2012 Jun 1;125(Pt 11):2665-74. doi: 10.1242/jcs.098954. Epub 2012 Feb 22.
- Gabai V.L., Meng L., Mills T., Benjamin I.J., and Sherman M.Y. Heat shock Transcription Factor Hsf1 is involved in tumor progression by regulating HIF-1 and RNA-binding Protein HuR. (2012) Mol.Cell Biol., 32: 929-940.
- Gong H. , Romanova N.V, Allen K.D., Chandramowlishwaran P., Gokhale K., Newnam G.P, Mieczkowski P., Sherman M.Y. and Chernoff Y.O. Polyglutamine toxicity is controlled by prion composition and gene dosage in yeast. (2012) PLOS Genetics, 8:2634.
- Sherman M.Y., Meng L., Stampfer M., Gabai V.L., and Yaglom J.A. Oncogenes induce senescence with incomplete growth arrest and suppress the DNA damage response. (2011) Aging Cell, 10:949-61.
- Sherman M.Y. Proteotoxic stress targeted therapy (PSTT). (2011) Oncotarget 2:356-7.
- Wang Z, Gall JM, Bonegio RG, Havasi A, Hunt CR, Sherman MY, Schwartz JH, Borkan SC. Induction of heat shock protein 70 inhibits ischemic renal injury. (2011) Kidney Int. 79:861-70.
- Meng L., Hunt C., Yaglom J.A., Gabai V.L., Sherman M.Y. Heat shock protein Hsp72 plays an essential role in Her2-induced mammary tumorigenesis. (2011) Oncogene. 30:2836-45.
- Meng L, Gabai V.L and Sherman M.Y. HER2-induced neoplastic transformation and tumorigenesis requires heat shock transcription factor HSF1. (2010) Oncogene, 29:5204-13
- Gabai V.L., O’Callaghan-Sunol C., Sherman M.Y. and Yaglom J.A. Genotoxic stresses fail to induce γ-H2AX in tumor cells with activated senescence signaling. (2010) Oncogene, 29:1952-62.
- Meriin A.B., Wang Y. and Sherman M.Y. Isolation of aggresomes and other large aggregates. (2010) Current protocols in Cell Biology, Chapter 3:Unit 3.38.1-9.
- Sherman M.Y. Major Heat Shock Protein Hsp72 Controls Oncogene-Induced Senescence. (2010) Ann.NY Acad. Sci., 1197:152-157.