Defining Transcription Factor-Chromatin-Remodeling Complex Interactions in Cancer: New Mechanisms and Therapeutic Opportunities


2019 Emerging Leader Award

Cigall Kadoch, PhD, Dana-Farber Cancer Institute

Cigall Kadoch, PhD

Dr. Kadoch is studying the protein complexes that determine and alter DNA structure and accessibility to understand their importance in leukemia and lymphoma. In this project, Dr. Kadoch is using multidisciplinary approaches to interrogate the structure and function of the mSWI/SNF complex to reveal its role in tumor initiation and response to treatment. Dr. Kadoch and her team will define the contributions of mSWI/SNF subunits, domains, and associated transcription factors to recruitment of the complex to chromatin, as well as their role in the activity of the complex, opening new opportunities for therapeutic intervention. Dr. Kadoch is Assistant Professor of Pediatric Oncology at the Dana-Farber Cancer Institute, Assistant Professor of Biological Chemistry and Molecular Biology at Harvard Medical School, and Institute Member and Epigenomics Program Co-Director at the Broad Institute of MIT and Harvard. She was awarded a PhD and completed postdoctoral training at the Stanford University School of Medicine.

PUBLISHED RESEARCH

Mashtalir N, Suzuki H, Farrell DP, Sankar A, Luo J, Filipovski M, D’Avino AR, St Pierre R, Valencia AM, Onikubo T, Roeder RG, Han Y, He Y, Ranish JA, DiMaio F, Walz T, Kadoch C. A Structural Model of the Endogenous Human BAF Complex Informs Disease Mechanisms. Cell. 2020.

Mashtalir N, Dao HT, Sankar A, Liu H, Corin AJ, Bagert JD, Ge EJ, D’Avino AR, Filipovski M, Michel BC, Dann GP, Muir TW, Kadoch C. Chromatin landscape signals differentially dictate the activities of mSWI/SNF family complexes. Science. 2021.

Dao HT, Liu H, Mashtalir N, Kadoch C, Muir TW. Synthesis of Oriented Hexasomes and Asymmetric Nucleosomes Using a Template Editing Process. J Am Chem Soc. 2022.

Wei J, Patil A, Collings CK, Alfajaro MM, Liang Y, Cai WL, Strine MS, Filler RB, DeWeirdt PC, Hanna RE, Menasche BL, Ökten A, Peña-Hernández MA, Klein J, McNamara A, Rosales R, McGovern BL, Luis Rodriguez M, García-Sastre A, White KM, Qin Y, Doench JG, Yan Q, Iwasaki A, Zwaka TP, Qi J, Kadoch C, Wilen CB. Pharmacological disruption of mSWI/SNF complex activity restricts SARS-CoV-2 infection. Nat Genet. 2023.

Battistello E, Hixon KA, Comstock DE, Collings CK, Chen X, Rodriguez Hernaez J, Lee S, Cervantes KS, Hinkley MM, Ntatsoulis K, Cesarano A, Hockemeyer K, Haining WN, Witkowski MT, Qi J, Tsirigos A, Perna F, Aifantis I, Kadoch C. Stepwise activities of mSWI/SNF family chromatin remodeling complexes direct T cell activation and exhaustion. Mol Cell. 2023.

Patil A, Strom AR, Paulo JA, Collings CK, Ruff KM, Shinn MK, Sankar A, Cervantes KS, Wauer T, St Laurent JD, Xu G, Becker LA, Gygi SP, Pappu RV, Brangwynne CP, Kadoch C. A disordered region controls cBAF activity via condensation and partner recruitment. Cell. 2023.

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