Immunology Faculty Member - Cigall Kadoch, PhD

Cigall Kadoch, PhD

Dana Farber Cancer Institute
Dana Building, Room D620
450 Brookline Avenue
Boston, MA 02115
Tel: 617-632-3789
Email: cigall_kadoch@dfci.harvard.edu



Our laboratory is centered in understanding the structure and function of ATP-dependent chromatin remodeling complexes, with an emphasis on their roles in human disease. Recent exome- and genome-wide sequencing studies in human cancer have unmasked a striking frequency of mutations in the genes encoding subunits of the mammalian SWI/SNF (mSWI/SNF) family of chromatin remodeling complexes. In addition, mSWI/SNF complexes serve as critical mediators of cell signaling pathways, metabolism, and response to various therapeutic approaches, including immunotherapy (checkpoint blockade). Our laboratory uses biochemistry, structural biology, systems biology, and genomics-based approaches to define mSWI/SNF-mediated chromatin and gene regulatory mechanisms and to inform new strategies for therapeutic development in cancer, neurodevelopmental disorders, and other diseases. 



Last Update: 1/28/2019



Publications


1. Michel BC*, D’Avino AR*, Cassel SH*, Mashtalir N, McKenzie ZM, McBride MJ, Valencia AM, Zhou Q, Bocker M, Soares LMM, Pan J, Remillard DI, Lareau CA, Zullow HJ, Fortoul N, Gray NS, Bradner JE, Chan H, Kadoch C. A non-canonical SWI/SNF complex is a synthetic lethal target in cancers driven by BAF complex perturbation. Nat Cell Biol. 2018 Dec;20(12):1410-1420.
2. Mashtalir N, D’Avino AR*, Michel BC*, Luo J, Pan J, Otto JE, Zullow HJ, McKenzie MZ, Kubiak RL, St. Pierre R, Valencia AM, Poynter SJ, Cassel SH, Ranish JA, Kadoch C. Modular organization and assembly of SWI/SNF family chromatin remodeling complexes. Cell. 2018 Nov 15;175(5):1272-1288.e20.
3. Sandoval GJ, Pulice, J, Schenone M, Takeda DY, Pop, M, McBride MJ, Boulay GS, Rivera MN, Hahn WC, Kadoch C. Binding of TMPRSS2-ERG to mSWI/SNF (BAF) complexes mediates prostate oncogenesis. Molecular Cell. 2018 Aug 16; 71(4):554-566.
4. McBride M, Pulice JL, Nakayama RT, Beird HC, Ingram DR, D’Avino AR, Shern JF, Charville GR, Hornick JL, Araujo D, Wang W, Tsai J, Yeagley M, Wagner AJ, Futreal AP, Khan J, Lazar AJ, Kadoch C. The SS18-SSX fusion oncoprotein hijacks BAF complex targeting and function to drive synovial sarcoma. Cancer Cell. 2018 Jun 33; 6:1128-1141.
5. Pan J, Meyers RM, Michel BC, Mashtalir N, Sizemore A, Wells JN, Cassel SH, Vasquez F, Weir BA, Hahn WC, Marsh JA, Tsherniak A, Kadoch C. Functional analysis of mammalian protein complexes using genome-scale fitness screens. Cell Systems. 2018 May 6(5): 555-568.
6. Nakayama RT, Pulice JL, Valencia AM, McBride MJ, McKenzie ZM, Gillespie MJ, Ku WL, Teng M, Cui K, Williams RT, Cassel SH, Qing H, Widmer CJ, Demetri GD, Irizarry RA, Zhao K, Ranish JA, Kadoch C. SMARCB1 is required for widespread BAF complex-mediated activation of enhancers and bivalent promoters. Nature Genetics. 2017 Nov 49(11):1613-1623.
7. Boulay G, Sandoval GJ, Riggi N, Iyer S, Buisson R, Naigles B, Awad ME, Rengarajan S, Volorio A, McBride MJ, Broye LC, Zou L, Stamenkovic I, Kadoch C*, Rivera MN*. Cancer-specific retargeting of BAF complexes by a prion-like domain. Cell. 2017 Sep 171(1): 163-178. *indicates co-corresponding authors.




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