Chemical Biology Program
The Gabriela Chiosis Lab
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 structurally, dynamically and functionally 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.
The epichaperome is an integrated chaperome network that facilitates tumour survival. Rodina A, Wang T, Yan P, Gomes ED, Dunphy MP, Pillarsetty N, Koren J, Gerecitano JF, Taldone T, Zong H, Caldas-Lopes E, Alpaugh M, Corben A, Riolo M, Beattie B, Pressl C, Peter RI, Xu C, Trondl R, Patel HJ, Shimizu F, Bolaender A, Yang C, Panchal P, Farooq MF, Kishinevsky S, Modi S, Lin O, Chu F, Patil S, Erdjument-Bromage H, Zanzonico P, Hudis C, Studer L, Roboz GJ, Cesarman E, Cerchietti L, Levine R, Melnick A, Larson SM, Lewis JS, Guzman ML, Chiosis G. Nature. 2016 Oct 5. doi: 10.1038/nature19807.
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]
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.
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.
Gabriela Chiosis, PhD
- The Chiosis lab uses a unique chemical biology approach to understand, diagnose, and treat cellular processes associated with chronic molecular stress, with the ultimate goal of developing novel therapeutic options for use in the clinic.
- PhD, Columbia University
- 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
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Gabriela Chiosis discloses the following relationships and financial interests:
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