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?
- Graduate Faculty (Primary Mentor of Grad Students), Boston University School of Medicine, Division of Graduate Medical Sciences
- Moscow State University, PhD
- Moscow State University, MS
- Published on 2/14/2018
Yaglom JA, Wang Y, Li A, Li Z, Monti S, Alexandrov I, Lu X, Sherman MY. Cancer cell responses to Hsp70 inhibitor JG-98: Comparison with Hsp90 inhibitors and finding synergistic drug combinations. Sci Rep. 2018 Feb 14; 8(1):3010. PMID: 29445088.
- Published on 9/26/2017
Gabai VL, Meng L, Kim G, Mills TA, Benjamin IJ, Sherman MY. Correction for Gabai et al., "Heat Shock Transcription Factor Hsf1 Is Involved in Tumor Progression via Regulation of Hypoxia-Inducible Factor 1 and RNA-Binding Protein HuR". Mol Cell Biol. 2017 Oct 15; 37(20). PMID: 28951485.
- Published on 8/3/2017
Halenova T, Savchuk O, Ostapchenko L, Chursov A, Fridlyand N, Komissarov AB, Venanzi F, Kolesnikov SI, Sufianov AA, Sherman MY, Gabai VL, Shneider AM. P62 plasmid can alleviate diet-induced obesity and metabolic dysfunctions. Oncotarget. 2017 Aug 22; 8(34):56030-56040. PMID: 28915571.
- Published on 5/23/2017
McFarland CD, Yaglom JA, Wojtkowiak JW, Scott JG, Morse DL, Sherman MY, Mirny LA. The Damaging Effect of Passenger Mutations on Cancer Progression. Cancer Res. 2017 Sep 15; 77(18):4763-4772. PMID: 28536279.
- Published on 1/15/2017
Athanasiou D, Aguila M, Opefi CA, South K, Bellingham J, Bevilacqua D, Munro PM, Kanuga N, Mackenzie FE, Dubis AM, Georgiadis A, Graca AB, Pearson RA, Ali RR, Sakami S, Palczewski K, Sherman MY, Reeves PJ, Cheetham ME. Rescue of mutant rhodopsin traffic by metformin-induced AMPK activation accelerates photoreceptor degeneration. Hum Mol Genet. 2017 Jan 15; 26(2):305-319. PMID: 28065882.
- Published on 8/8/2016
Gabai VL, Yaglom JA, Wang Y, Meng L, Shao H, Kim G, Colvin T, Gestwicki J, Sherman MY. Anticancer Effects of Targeting Hsp70 in Tumor Stromal Cells. Cancer Res. 2016 Oct 15; 76(20):5926-5932. PMID: 27503927.
- Published on 5/10/2016
Lee do H, Sherman MY, Goldberg AL. The requirements of yeast Hsp70 of SSA family for the ubiquitin-dependent degradation of short-lived and abnormal proteins. Biochem Biophys Res Commun. 2016 Jun 17; 475(1):100-6. PMID: 27178214.
- Published on 8/24/2015
Zaarur N, Xu X, Lestienne P, Meriin AB, McComb M, Costello CE, Newnam GP, Ganti R, Romanova NV, Shanmugasundaram M, Silva ST, Bandeiras TM, Matias PM, Lobachev KS, Lednev IK, Chernoff YO, Sherman MY. RuvbL1 and RuvbL2 enhance aggresome formation and disaggregate amyloid fibrils. EMBO J. 2015 Sep 14; 34(18):2363-82. PMID: 26303906.
- Published on 2/28/2015
Sabbieti MG, Agas D, Capitani M, Marchetti L, Concetti A, Vullo C, Catone G, Gabai V, Shifrin V, Sherman MY, Shneider A, Venanzi FM. Plasmid DNA-coding p62 as a bone effective anti-inflammatory/anabolic agent. Oncotarget. 2015 Feb 28; 6(6):3590-9. PMID: 25668818.
- Published on 2/9/2015
Gong J, Weng D, Eguchi T, Murshid A, Sherman MY, Song B, Calderwood SK. Targeting the hsp70 gene delays mammary tumor initiation and inhibits tumor cell metastasis. Oncogene. 2015 Oct; 34(43):5460-71. PMID: 25659585.
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