Featured Publications
Bold denotes authors in the Kadoch Lab
Mammalian SWI/SNF complex activity regulates POU2F3 and constitutes a targetable dependency in small cell lung cancer
Leslie Duplaquet*, Kevin So*, Alexander W Ying, Shreoshi Pal Choudhuri, Xinyue Li, Grace D Xu, Yixiang Li, Xintao Qiu, Rong Li, Shilpa Singh, Xiaoli S Wu, Seth Hamilton, Victor D Chien, Qi Liu, Jun Qi, Tim D D Somerville, Hillary M Heiling, Emanuele Mazzola, Yenarae Lee, Thomas Zoller, Christopher R Vakoc, John G Doench, William C Forrester, Tinya Abrams, Henry W Long, Matthew J Niederst, Benjamin J Drapkin, Cigall Kadoch**, Matthew G Oser**
A disordered region controls cBAF activity via condensation and partner recruitment
Ajinkya Patil*, Amy R Strom*, Joao A Paulo, Clayton K Collings, Kiersten M Ruff, Min Kyung Shinn, Akshay Sankar, Kasey S Cervantes, Tobias Wauer, Jessica D St Laurent, Grace Xu, Lindsay A Becker, Steven P Gygi, Rohit V Pappu, Clifford P Brangwynne** & Cigall Kadoch**
Mammalian SWI/SNF chromatin remodeling complexes promote tyrosine kinase inhibitor resistance in EGFR-mutant lung cancer
Fernando J de Miguel*, Claudia Gentile*, William W Feng, Shannon J Silva, Akshay Sankar, Francisco Exposito, Wesley L Cai, Mary Ann Melnick, Camila Robles-Oteiza, Madeline M Hinkley, Jeanelle A Tsai, Antja-Voy Hartley, Jin Wei, Anna Wurtz, Fangyong Li, Maria I Toki, David L Rimm, Robert Homer, Craig B Wilen, Andrew Z Xiao, Jun Qi, Qin Yan, Don X Nguyen, Pasi A Jänne, Cigall Kadoch**, Katerina A Politi**
Landscape of mSWI/SNF chromatin remodeling complex perturbations in neurodevelopmental disorders
Alfredo M. Valencia, Akshay Sankar, Pleuntje J. van der Sluijs, F. Kyle Satterstrom, Jack Fu, Michael E. Talkowski, Samantha A. Schrier Vergano, Gijs W. E. Santen & Cigall Kadoch
Structural and functional properties of mSWI/SNF chromatin remodeling complexes revealed through single-cell perturbation screens (Molecular Cell, 2023)
Jordan E. Otto, Oana Ursu, Alexander P. Wu, Evan B. Winter, Michael S. Cuoco, Sai Ma, Kristin Qian, Brittany C. Michel, Jason D. Buenrostro, Bonnie Berger, Aviv Regev, and Cigall Kadoch
Stepwise activities of mSWI/SNF family chromatin remodeling complexes direct T cell activation and exhaustion (Molecular Cell, 2023)
Elena Battistello, Kimberlee A. Hixon, Dawn E. Comstock, Clayton K. Collings, Xufeng Chen, Javier Rodriguez Hernaez, Soobeom Lee, Kasey S. Cervantes, Madeline M. Hinkley, Konstantinos Ntatsoulis, Annamaria Cesarano, Kathryn Hockemeyer, W. Nicholas Haining, Matthew T. Witkowski, Jun Qi, Aristotelis Tsirigos, Fabiana Perna, Iannis Aifantis, and Cigall Kadoch
Pharmacological disruption of mSWI/ SNF complex activity restricts SARS-CoV-2 infection (Nature Genetics, 2023)
Jin Wei, Ajinkya Patil, Clayton K. Collings, Mia Madel Alfajaro, Yu Liang, Wesley L. Cai, Madison S. Strine, Renata B. Filler, Peter C. DeWeirdt, Ruth E. Hanna, Bridget L. Menasche, Arya Ökten, Mario A. Peña-Hernández, Jon Klein, Andrew McNamara, Romel Rosales, Briana L. McGovern, M. Luis Rodriguez, Adolfo García-Sastre, Kris M. White, Yiren Qin, John G. Doench, Qin Yan, Akiko Iwasaki, Thomas P. Zwaka, Jun Qi, Cigall Kadoch & Craig B. Wilen
Chromatin landscape signals differentially dictate the activities of mSWI/SNF family complexes (Science, 2021)
Nazar Mashtalir, Hai T Dao, Akshay Sankar, Hengyuan Liu, Aaron J Corin, John D Bagert, Eva J Ge, Andrew R D'Avino, Martin Filipovski, Brittany C Michel, Geoffrey P Dann, Tom W Muir , Cigall Kadoch
A Structural Model of the Endogenous Human BAF Complex Informs Disease Mechanisms (Cell, 2020)
Nazar Mashtalir, Hiroshi Suzuki, Daniel P Farrell, Akshay Sankar, Jie Luo, Martin Filipovski, Andrew R D'Avino, Roodolph St Pierre, Alfredo M Valencia, Takashi Onikubo, Robert G Roeder, Yan Han, Yuan He, Jeffrey A Ranish, Frank DiMaio, Thomas Walz, Cigall Kadoch
The nucleosome acidic patch and H2A ubiquitination underlie mSWI/SNF recruitment in synovial sarcoma (Nature Structural & Molecular Biology, 2020)
Matthew J McBride, Nazar Mashtalir, Evan B Winter, Hai T Dao, Martin Filipovski, Andrew R D'Avino, Hyuk-Soo Seo, Neil T Umbreit, Roodolph St Pierre, Alfredo M Valencia, Kristin Qian, Hayley J Zullow, Jacob D Jaffe, Sirano Dhe-Paganon, Tom W Muir, Cigall Kadoch
Recurrent SMARCB1 Mutations Reveal a Nucleosome Acidic Patch Interaction Site That Potentiates mSWI/SNF Complex Chromatin Remodeling (Cell, 2019)
Alfredo M Valencia, Clayton K Collings, Hai T Dao, Roodolph St Pierre, Yung-Chih Cheng, Junwei Huang, Zhen-Yu Sun, Hyuk-Soo Seo, Nazar Mashtalir, Dawn E Comstock, Olubusayo Bolonduro, Nicholas E Vangos, Zoe C Yeoh, Mary Kate Dornon, Crystal Hermawan, Lee Barrett, Sirano Dhe-Paganon, Clifford J Woolf, Tom W Muir, Cigall Kadoch
The ATPase module of mammalian SWI/SNF family complexes mediates subcomplex identity and catalytic activity-independent genomic targeting
(Nature Genetics, 2019)
Joshua Pan, Zachary M McKenzie, Andrew R D'Avino, Nazar Mashtalir, Caleb A Lareau, Roodolph St Pierre, Lu Wang, Ali Shilatifard, Cigall Kadoch
A non-canonical SWI/SNF complex is a synthetic lethal target in cancers driven by BAF complex perturbation (Nature Cell Biology, 2018)
Brittany C. Michel*, Andrew R. D’Avino, Seth H. Cassel*, Nazar Mashtalir, Zachary M. McKenzie, Matthew J. McBride, Alfredo M. Valencia, Qianhe Zhou, Michael Bocker, Luis M. M. Soares, Joshua Pan, David I. Remillard, Caleb A. Lareau, Hayley J. Zullow, Nora Fortoul, Nathanael S. Gray, James E. Bradner, Ho Man Chan and Cigall Kadoch. (* These authors contributed equally)
Modular Organization and Assembly of SWI/SNF Family Chromatin Remodeling Complexes (Cell, 2018)
Nazar Mashtalir, Andrew R. D’Avino, Brittany C. Michel, Jie Luo, Joshua Pan, Jordan E. Otto, Hayley J. Zullow, Zachary M. McKenzie, Rachel L. Kubiak, Roodolph St. Pierre, Alfredo M. Valencia, Steven J. Poynter, Seth H. Cassel, Jeffrey A. Ranish, and Cigall Kadoch
Binding of TMPRSS2-ERG to BAF Chromatin Remodeling Complexes Mediates Prostate Oncogenesis (Molecular Cell, 2018)
Sandoval, G.J.*, Pulice, J.L.*, Pakula, H., Schenone, M.A., Takeda, D.Y., Pop, M., Boulay, G., Williamson, K., McBride, M.J., St. Pierre, R., Hartman, E., Garraway, L.A., Carr, S.A., Li, Z., Rivera, M.N., Ronco, L., Hahn, W.C.**, and Kadoch, C.** Binding of TMPRSS2-ERG to BAF chromatin remodeling complexes mediates prostate oncogenesis (2018). Molecular Cell 71, 554-566 doi:10.1016/j.molcel.2018.06.040
(* These authors contributed equally, ** Corresponding authors)
Article coverage:
Cancer Discovery research highlight
The SS18-SSX Fusion Oncoprotein Hijacks BAF Complex Targeting and Function to Drive Synovial Sarcoma (Cancer Cell, 2018)
McBride, M.J.*, Pulice, J.L.*, Beird, H.C., Ingram, D.R., D'Avino, A.R., Shern, J.F., Charville, G.W., Hornick, J.L., Nakayama, R.T., Garcia-Rivera, E.M., Araujo, D.M., Wang, W., Tsai, J., Yeagley, M., Wagner, A.J., Futreal, P.A., Khan, J., Lazar, A.J., and Kadoch, C.** The SS18-SSX Fusion Oncoprotein Hijacks BAF Complex Targeting and Function to Drive Synovial Sarcoma (2018). Cancer Cell 33, 1128-1141 doi:10.1016/j.ccell.2018.05.002 (* These authors contributed equally, ** Corresponding author)
Article Coverage:
Cancer Cell preview
Cancer Discovery research highlight
Interrogation of Mammalian Protein Complex Structure, Function, and Membership Using Genome-Scale Fitness Screens (Cell Systems, 2018)
Pan, J.*, Meyers, R.M.*, Michel, B.C., Mashtalir, N.M., Sizemore, A.E., Wells, J.N., Cassel, S.H., Vazquez, F., Weir, B.A., Hahn, W.C., Marsh, J.A., Tserniak, A., and Kadoch, C.** Interrogation of Mammalian Protein Complex Structure, Function, and Membership Using Genome-Scale Fitness Screens (2018). Cell Systems. 6, 555-568 doi:10.1016/j.cels.2018.04.011 (* These authors contributed equally, ** Corresponding author)
SMARCB1 is required for widespread BAF complex-mediated activation of enhancers and bivalent promoters (Nature Genetics, 2017)
Nakayama, R.T.*, Pulice, J.L.*, Valencia, A.M.*, McBride, M.J., McKenzie, Z.M., Gillespie, M., Ku, W.L., Teng, M., Cui, K., Williams, R.T., Cassel, S.H., He, Q., Widmer, C.J., Demetri, G.D., Irizaary, R.A., Zhao, K., Ranish, J., and Kadoch, C.** SMARCB1 is required for widespread BAF complex– mediated activation of enhancers and bivalent promoters (2017). Nat. Genet. 49, 1613-1623 doi:10.1038/ng.3958 (* These authors contributed equally, ** Corresponding authors)
Cancer-Specific Retargeting of BAF Complexes by a Prion-like Domain (Cell, 2017)
Boulay, G.*, Sandoval, G.J.*, Riggi, N., Iyer, S., Buisson, R. Naigles, B., Awad, M.E., Rengarajan, S., Volorio, A., McBride, M.J., Broye, L.C., Zou, L., Stamenkovic, I., Kadoch, C.**, and Rivera, M.N.**. (2017) Cancer-Specific Retargeting of BAF Complexes by a Prion-like Domain. Cell. 171, 163–178 doi:10.1016/j.cell.2017.07.036 (* These authors contributed equally, ** Corresponding authors)
Article coverage:
Cell preview
Dynamics of BAF-Polycomb complex opposition on heterochromatin in normal and oncogenic states (Nature Genetics, 2017)
Kadoch, C.*, Williams, R.T., Calarco, J.P., Miller, E.L., Weber, C.M., Braun, S.M.G., Pulice, J.L., Chory, E.J. and Crabtree. G.R.* (2016) Dynamics of BAF-Polycomb complex opposition on heterochromatin in normal and oncogenic states. Nat. Genet. 49, 213-222. doi:10.1038/ng.3734 (*Corresponding authors)
Nature Genetics preview
Proteomic and bioinformatic analysis of the mammalian SWI/SNF complexes identifies extensive roles in human malignancy (Nature Genetics, 2013)
Kadoch, C., Hargreaves, D.C., Hodges, C., Elias, L., Ho, L., Ranish, J. and Crabtree, G.R. (2013) Proteomic and bioinformatic analysis of the mammalian SWI/SNF complexes identifies extensive roles in human malignancy. Nat. Genet. 45, 592-602. doi:10.1038/ng.2628
Reversible disruption of mSWI/SNF (BAF) complexes by the SS18-SSX oncogenic fusion in synovial sarcoma (Cell, 2013)
Kadoch, C. and Crabtree, G.R. (2013). Reversible disruption of mSWI/SNF (BAF) complexes by the SS18-SSX oncogenic fusion in synovial sarcoma. Cell 153, 71-85. doi:10.1016/j.cell.2013.02.036
Cell preview
Selected Cover Art
Cancer Cell, June 2018 Issue (33/6)
On the cover: Synovial sarcoma is a rare pediatric cancer in which the hallmark SS18-SSX fusion incorporates into and disrupts BAF complexes to drive tumorigenesis. In this issue, McBride et al. (pp. 1128–1141) demonstrate that the SS18-SSX fusion protein (pirate) confers both gain and loss of genome-wide BAF complex targeting, with BAF complexes (boat) hijacked away from enhancers (green islands) to broad polycomb-repressed domains (gray islands) to activate oncogenic transcription. Cover art by Eric Smith.
Article: McBride, M.J.*, Pulice, J.L.*, Beird, H.C., Ingram, D.R., D'Avino, A.R., Shern, J.F., Charville, G.W., Hornick, J.L., Nakayama, R.T., Garcia-Rivera, E.M., Araujo, D.M., Wang, W., Tsai, J., Yeagley, M., Wagner, A.J., Futreal, P.A., Khan, J., Lazar, A.J., and Kadoch, C.** The SS18-SSX Fusion Oncoprotein Hijacks BAF Complex Targeting and Function to Drive Synovial Sarcoma (2018). Cancer Cell. doi:10.1016/j.ccell.2018.05.002 (* These authors contributed equally, ** Corresponding author)
Cell Systems, May 2018 Issue (6/5)
On the cover: Fitness landscapes. In this issue, Pan et al. (555–568) characterize differential fitness responses to genetic perturbations in cancer cell lines and demonstrate the utility of these fitness profiles in studying gene function. Inspired by the classic album cover of Joy Division's Unknown Pleasures record and enabled by Claus Wilke's R-package “ggridges,” the cover image is an artistic interpretation generated using real data from the fitness responses of 342 cancer cell lines to knockout of individual genes, each represented by a trace. Image credit: Robin Meyers, Joshua Pan, and Eric Smith.
Article: Pan, J.*, Meyers, R.M.*, Michel, B.C., Mashtalir, N.M., Sizemore, A.E., Wells, J.N., Cassel, S.H., Vazquez, F., Weir, B.A., Hahn, W.C., Marsh, J.A., Tserniak, A., and Kadoch, C.** Interrogation of Mammalian Protein Complex Structure, Function, and Membership Using Genome-Scale Fitness Screens (2018). Cell Systems. doi:10.1016/j.cels.2018.04.011 (* These authors contributed equally, ** Corresponding authors)
Full Publication List
2018
Brittany C. Michel*, Andrew R. D’Avino, Seth H. Cassel*, Nazar Mashtalir, Zachary M. McKenzie, Matthew J. McBride, Alfredo M. Valencia, Qianhe Zhou, Michael Bocker, Luis M. M. Soares, Joshua Pan, David I. Remillard, Caleb A. Lareau, Hayley J. Zullow, Nora Fortoul, Nathanael S. Gray, James E. Bradner, Ho Man Chan and Cigall Kadoch. A non-canonical SWI/SNF complex is a synthetic lethal target in cancers driven by BAF complex perturbation (2018) Nature Cell Biology. (* These authors contributed equally)
Nazar Mashtalir, Andrew R. D’Avino, Brittany C. Michel, Jie Luo, Joshua Pan, Jordan E. Otto, Hayley J. Zullow, Zachary M. McKenzie, Rachel L. Kubiak, Roodolph St. Pierre, Alfredo M. Valencia, Steven J. Poynter, Seth H. Cassel, Jeffrey A. Ranish, and Cigall Kadoch. Modular Organization and Assembly of SWI/SNF Family Chromatin Remodeling Complexes (2018). Cell.
Sandoval, G.J.*, Pulice, J.L.*, Pakula, H., Schenone, M.A., Takeda, D.Y., Pop, M., Boulay, G., Williamson, K., McBride, M.J., St. Pierre, R., Hartman, E., Garraway, L.A., Carr, S.A., Li, Z., Rivera, M.N., Ronco, L., Hahn, W.C.**, and Kadoch, C.** Binding of TMPRSS2-ERG to BAF chromatin remodeling complexes mediates prostate oncogenesis (2018). Molecular Cell 71, 554-566 doi:10.1016/j.molcel.2018.06.040 (* These authors contributed equally, ** Corresponding authors)
McBride, M.J.*, Pulice, J.L.*, Beird, H.C., Ingram, D.R., D'Avino, A.R., Shern, J.F., Charville, G.W., Hornick, J.L., Nakayama, R.T., Garcia-Rivera, E.M., Araujo, D.M., Wang, W., Tsai, J., Yeagley, M., Wagner, A.J., Futreal, P.A., Khan, J., Lazar, A.J., and Kadoch, C.** The SS18-SSX Fusion Oncoprotein Hijacks BAF Complex Targeting and Function to Drive Synovial Sarcoma (2018). Cancer Cell. 33, 1128-1141 doi:10.1016/j.ccell.2018.05.002 (* These authors contributed equally, ** Corresponding author)
Pan, J.*, Meyers, R.M.*, Michel, B.C., Mashtalir, N.M., Sizemore, A.E., Wells, J.N., Cassel, S.H., Vazquez, F., Weir, B.A., Hahn, W.C., Marsh, J.A., Tserniak, A., and Kadoch, C.** Interrogation of Mammalian Protein Complex Structure, Function, and Membership Using Genome-Scale Fitness Screens (2018). Cell Systems 5, 555-568 doi:10.1016/j.cels.2018.04.011 (* These authors contributed equally, ** Corresponding author)
2017
Otto, J.A., and Kadoch, C. (2017). A Two-Faced mSWI/SNF Subunit: Dual Roles for ARID1A in Tumor Suppression and Oncogenicity in the Liver. Cancer Cell 32, 542-543 doi:10.1016/j.ccell.2017.10.014 (Preview Article)
Nakayama, R.T.*, Pulice, J.L.*, Valencia, A.M.*, McBride, M.J., McKenzie, Z.M., Gillespie, M., Ku, W.L., Teng, M., Cui, K., Williams, R.T., Cassel, S.H., He, Q., Widmer, C.J., Demetri, G.D., Irizaary, R.A., Zhao, K., Ranish, J., and Kadoch, C.** SMARCB1 is required for widespread BAF complex– mediated activation of enhancers and bivalent promoters (2017). Nat. Genet. 49, 1613-1623 doi:10.1038/ng.3958 (* These authors contributed equally, ** Corresponding authors)
Boulay, G.*, Sandoval, G.J.*, Riggi, N., Iyer, S., Buisson, R. Naigles, B., Awad, M.E., Rengarajan, S., Volorio, A., McBride, M.J., Broye, L.C., Zou, L., Stamenkovic, I., Kadoch, C.**, and Rivera, M.N.**. (2017) Cancer-Specific Retargeting of BAF Complexes by a Prion-like Domain. Cell. 171, 163–178 doi:10.1016/j.cell.2017.07.036 (* These authors contributed equally, ** Corresponding authors)
Michel, B.C., and Kadoch, C. (2017). A SMARCD2-containing mSWI/SNF complex is required for granulopoiesis. Nat. Genet. 49, 655-657. doi:10.1038/ng.3853 (News and Views Article)
Pulice, J.L. and Kadoch, C. (2017). Composition and Function of Mammalian SWI/SNF Chromatin Remodeling Complexes in Human Disease. Cold Spring Harb. Sym. doi:10.1101/sqb.2016.81.031021
St. Pierre, R. and Kadoch, C. (2017). Mammalian SWI/SNF complexes in cancer: emerging therapeutic opportunities. Curr. Opin. Genet. Dev. doi:10.1016/j.gde.2017.02.004
Miller, E.L., Hargreaves, D.C., Kadoch, C., Chang, C.Y., Calarco, J.P., Hodges, C., Buenrostro, J.D., Cui, K., Greenleaf, W.J., Zhao, K., and Crabtree, G.R. (2017). TOP2 synergizes with BAF chromatin remodeling for both resolution and formation of facultative heterochromatin. Nat. Struct. Mol. Biol. 24, 344-352. doi:10.1038/nsmb.3384
Kadoch, C.*, Williams, R.T., Calarco, J.P., Miller, E.L., Weber, C.M., Braun, S.M.G., Pulice, J.L., Chory, E.J. and Crabtree. G.R.* (2017) Dynamics of BAF-Polycomb complex opposition on heterochromatin in normal and oncogenic states. Nat. Genet. 49, 213-222. doi:10.1038/ng.3734 (*Corresponding authors)
Stanton, B.Z., Hodges, C., Calarco, J.P., Braun, S.M.G., Ku, W.L., Kadoch, C., Zhao, K., and Crabtree, G.R. (2017) Smarca4 ATPase mutations disrupt direct eviction of PRC1 from chromatin. Nat. Genet. 49, 282-288, doi:10.1038/ng.3735
2013-2016
Poynter, S. and Kadoch, C. (2016) Polycomb and trithorax opposition in development and disease. WIREs Dev BIo. doi:10.1002/wdev.244
Kadoch, C. (2016) Lifting up the HAT: Synthetic lethal screening reveals a novel vulnerability at the CBP-p300 axis. Cancer Discovery. 6, 430. doi:10.1158/2159-8290.CD-16-0163 (Spotlight Article)
Kadoch, C., Copeland, R.A., and Keilhack, H. (2016) PRC2 and SWI/SNF chromatin remodeling complexes in health and disease. Biochemistry 55, 1600-1614. doi:10.1021/acs.biochem.5b01191
Kadoch, C. and Crabtree, G.R. (2015) Mammalian SWI/SNF chromatin remodeling complexes and cancer: mechanistic insights gained from human cancer. Sci. Adv. 1, e1500447. doi:10.1126/sciadv.1500447
Kadoch, C., Hargreaves, D.C., Hodges, C., Elias, L., Ho, L., Ranish, J. and Crabtree, G.R. (2013) Proteomic and bioinformatic analysis of the mammalian SWI/SNF complexes identifies extensive roles in human malignancy. Nat. Genet. 45, 592-602. doi:10.1038/ng.2628
Kadoch, C. and Crabtree, G.R. (2013). Reversible disruption of mSWI/SNF (BAF) complexes by the SS18-SSX oncogenic fusion in synovial sarcoma. Cell 153, 71-85. doi:10.1016/j.cell.2013.02.036
Bold denotes authors in the Kadoch Lab
*co-first author
**co-senior author