The goal of my program is to investigate the nature of chronic stress as it occurs in numerous diseases and aging. Our approach takes advantage of the way nature has evolved to control such stresses, and that is by a unique usage of the chaperome, referred to here as the chronic stress chaperome (CSC). The CSC is epigenetically and thermodynamically distinct from the housekeeping chaperome, and my lab has pioneered an approach to take advantage of such feature. By using innovative methods, we develop small molecule chemical tool sets specifically targeted to the CSC; these act as “sensors” of the CSC and, in turn, of the chronic stress-associated proteome. By the use of these unique tool sets we aim to understand, diagnose, and treat cellular processes associated with chronic stress. 

Publications

Identification of an allosteric pocket on human hsp70 reveals a mode of inhibition of this therapeutically important protein. Rodina A, Patel PD, Kang Y, Patel Y, Baaklini I, Wong MJ, Taldone T, Yan P, Yang C, Maharaj R, Gozman A, Patel MR, Patel HJ, Chirico W, Erdjument-Bromage H, Talele TT, Young JC, Chiosis G. Chem Biol. 2013 Dec 19;20(12):1469-80. doi: 10.1016/j.chembiol.2013.10.008. Epub 2013 Nov 14.

Paralog-selective Hsp90 inhibitors define tumor-specific regulation of HER2. Patel PD, Yan P, Seidler PM, Patel HJ, Sun W, Yang C, Que NS, Taldone T, Finotti P, Stephani RA, Gewirth DT, Chiosis G. Nat Chem Biol. 2013 Sep 1. doi: 10.1038/nchembio.1335. [Epub ahead of print]

Affinity-based proteomics reveal cancer-specific networks coordinated by Hsp90. Moulick K, Ahn JH, Zong H, Rodina A, Cerchietti L, Gomes DaGama EM, Caldas-Lopes E, Beebe K, Perna F, Hatzi K, Vu LP, Zhao X, Zatorska D, Taldone T, Smith-Jones P, Alpaugh M, Gross SS, Pillarsetty N, Ku T, Lewis JS, Larson SM, Levine R, Erdjument-Bromage H, Guzman ML, Nimer SD, Melnick A, Neckers L, Chiosis G. Nat Chem Biol. 2011 Sep 25;7(11):818-26. doi: 10.1038/nchembio.670.

Hsp90 inhibitor PU-H71, a multimodal inhibitor of malignancy, induces complete responses in triple-negative breast cancer models. Caldas-Lopes E, Cerchietti L, Ahn JH, Clement CC, Robles AI, Rodina A, Moulick K, Taldone T, Gozman A, Guo Y, Wu N, de Stanchina E, White J, Gross SS, Ma Y, Varticovski L, Melnick A, Chiosis G. Proc Natl Acad Sci U S A. 2009 May 19;106(20):8368-73. doi: 10.1073/pnas.0903392106. Epub 2009 May 5.

Selective compounds define Hsp90 as a major inhibitor of apoptosis in small-cell lung cancer. Rodina A, Vilenchik M, Moulick K, Aguirre J, Kim J, Chiang A, Litz J, Clement CC, Kang Y, She Y, Wu N, Felts S, Wipf P, Massague J, Jiang X, Brodsky JL, Krystal GW, Chiosis G. Nat Chem Biol. 2007 Aug;3(8):498-507. Epub 2007 Jul 1.

Identification of potent water soluble purine-scaffold inhibitors of the heat shock protein 90. He H, Zatorska D, Kim J, Aguirre J, Llauger L, She Y, Wu N, Immormino RM, Gewirth DT, Chiosis G. J Med Chem. 2006 Jan 12;49(1):381-90.

Office phone:
646-888-2235
Office fax:
646-422-0416
Laboratory phone:
646-888-2216/2238
Selected Achievements

AACR – Cancer Research and Prevention Career Development Award in Translational Lung Cancer Research, in Memory of Duffy Wall

Susan G. Komen Breast Cancer Translational Research Award

Frederick R. Adler Chair for Junior Faculty

Award for Drug Discovery Research for Frontotemporal Dementia

Top 5 percent cited author in Biology and Biochemistry 2010 (analysis by Thomson Reuters)

Translated from bench-to-bedside the Hsp90 inhibitor PU-H71 and the non-invasive companion diagnostic 124I-PU-H71 PET assay