Raul Mostoslavsky

Research in the Mostoslavsky laboratory focuses on the crosstalk between chromatin dynamics and cellular metabolism. In particular, we have focused on sirtuins, a family of proteins first discovered in yeast that plays a critical role in many human diseases, including cancer. Most of our previous work involves the Sir2 mammalian homolog known as SIRT6, an enzyme with roles in compacting the DNA scaffolding structure known as chromatin. Our research indicates that SIRT6 modulates glucose metabolism and DNA repair and functions as a strong tumor suppressor gene. Using transgenic mouse models and other experimental systems, we are exploring the role of SIRT6 and metabolism in tumorigenesis and other disease processes, as well as trying to understand the crosstalk between metabolism and epigenetics. Our current projects involve understanding the molecular roles of chromatin in DNA repair, identifying chromatin and metabolic drivers of metastatic disease, and the crosstalk between metabolic pathways and chromatin structure.

Education

• National University of Tucuman, Argentina (1988 — 1994)
• Universidad Nacional de Tucumán (1988 — 1993)
• Doctor of Medicine (MD) University of Tucuman Argentina (1988 — 1993)

Selected Publications

Choi-J, Sebastian C, Ferrer C, Lewis C, Sade-Feldman M, Lasalle T, Gonye A, Lopez BCG, Abdelmoula W, Regan MS, Cetinbas, M, Pascual G, Wojtkiewicz GR, Silveira GG, Boon R, Ross KN, Tirosh I, Saladi SV, Ellisen LW, Sadreyev RI, Benitah SA, Agar NYR, Hacohen N, and Mostoslavsky R. A unique subset of glycolytic tumor propagating cells drives squamous cell carcinoma. Nature Metab. 2021, 3, 182-195.

Boon R, Silveira GG, and Mostoslavsky R. Nuclear Metabolism and the regulation of the epigenome. Nat. Metabolism. 2020 Nov;2(11):1190-1203.

Etchegaray JP, Chavez L, Huang Y, Ross KN, Choi J, Martinez-Pastor B, Walsh RM, Sommer CA, Lienhard M, Gladden A, Kugel S, Silberman DM, Ramaswamy S, Mostoslavsky G, Hochedlinger K, Goren A, Rao A, Mostoslavsky R. The histone deacetylase SIRT6 controls embryonic stem cell fate via TET-mediated production of 5-hydroxymethylcytosine. Nat Cell Biol. 2015 May;17(5):545-57.

Kugel, S., Sebastian, C., Fitamant, J., Ross, K.N., Saha, S.K., Jain, E., Gladden, A., Arora, K.S., Kato, Y., Rivera, M.N., Ramaswamy, S., Sadreyev, R.I., Goren, A., Deshpande, V., Bardeesy, N., and Mostoslavsky, R. SIRT6 suppresses pancreatic cancer through control of Lin28b. Cell, 2016 Jun 2;165(6):1401-15.

Toiber D, Erdel F, Bouazoune K, Silberman DM, Zhong L., Mulligan P, Sebastian C, Cosentino C, Martinez-Pastor B, Giacosa S, D’Urso A, Naar AM, Kingston R, Rippe K, and Mostoslavsky R. SIRT6 recruits SNF2H to DNA break sites, preventing genomic instability through chromatin remodeling. Molecular Cell. 2013 Aug 22;51(4):454-68.

Sebastian C, Zwaans BM, Silberman DM, Gymrek MA, Goren A, Zhong L, Ran O, Truelove J, Guimaraes AR, Toiber D, Cosentino C, Greenson JK, MacDonald AI, McGlynn L, Maxwell F, Edwards J, Giacosa S, Guccione E, Weisledder R, Bernstein BE, Regev A, Shiels PG, Lombard DB and Mostoslavsky R. The Histone Deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism. Cell. 2012 Dec 7;151(6):1185-99.