Xiaofeng Wang, PhD
Assistant Professor of Molecular and Systems Biology
Molecular and Systems Biology
Tsinghua University, Cancer Biology, Ph.D. '11
Sichuan University, Biological Sciences, B.S. '05
Molecular and Cellular Biology Graduate Programs
Program in Experimental and Molecular Medicine
1 Medical Center Dr
Lebanon NH 03756
Our work focuses on cancer epigenetics. We are particularly interested in studying a family of chromatin remodeling SWI/SNF(BAF) complexes, which are frequently mutated in a variety of human cancers. Our work is aimed to understand how these mutations cause cancer, focusing on the regulation of chromatin structure dynamics (SWI/SNF epigenome) and chromatin remodeler protein complex assembly (SWI/SNF interactome), as well as using genetic and chemical screens to identify potential therapeutic targets in human cancers.
We have found that SWI/SNF complex is essential for enhancer activation and super-enhancer maintenance, and certain subunits are crucial to maintain the stability and abundance of the complex in cancers (Nature Genetics, 2017; Nature Communications, 2017). It remains unclear how the complex regulates the enhancer landscapes in normal and cancer cells and how different subunits contribute to the complex assembly and targeting on chromatin. Meanwhile, using high-throughput genome-wide loss-of-function screens (shRNA and CRISPR-Cas9), we have found that SWI/SNF mutations create specific paralog dependencies in cancer (Nature Medicine 2014; Cancer Cell, 2014), pointing to potential therapeutic benefits.
Current research in the lab is focused on studying the genome-wide targeting of SWI/SNF complex in cancer and its role in regulating chromatin structures; identifying novel interacting proteins and co-regulators; searching for cancer specific vulnerabilities using genome-wide CRISPR-Cas9 screens.
SMARCB1 regulated SWI/SNF complex function in Malignant Rhabdoid Tumors
Wang X, Wang S, Troisi EC, Howard TP, Haswell JR, Wolf BK, Hawk WH, Ramos P, Oberlick EM, Tzvetkov EP, Vazquez F, Hahn WC, Park PJ, Roberts CWM. BRD9 defines a SWI/SNF sub-complex and constitutes a specific vulnerability in malignant rhabdoid tumors. Nat Commun. 2019 Apr 23;10(1):188. (view details in PubMed)
Howard TP, Arnoff TE, Song MR, Giacomelli AO, Wang X, Hong AL, Dharia NV, Wang S, Vazquez F, Pham MT, Morgan AM, Wachter F, Bird GH, Kugener G, Oberlick EM, Rees MG, Tiv HL, Hwang JH, Walsh KH, Cook A, Krill-Burger JM, Tsherniak A, Gokhale PC, Park PJ... MDM2 and MDM4 Are Therapeutic Vulnerabilities in Malignant Rhabdoid Tumors. Cancer Res. 2019 May 1;79(9):2404-2414. (view details in PubMed)
Wang X*, Lee RS*, Alver BH*, Haswell JR, Wang S, Mieczkowski J, Drier Y, Gillespie SM, Archer TC, Wu JN, Tzvetkov EP, Troisi EC, Pomeroy SL, Biegel JA, Tolstorukov MY, Bernstein BE, Park PJ, and Roberts CW. (*Co-first author) SMARCB1-mediated SWI/SNF complex function is essential for enhancer regulation. Nat Genet. 2017;49(2):289-295 . (view details in PubMed)
Mathur R, Alver BH, San Roman AK, Wilson BG, Wang X, Agoston AT, Park PJ, Shivdasani RA, Roberts CW. ARID1A loss impairs enhancer-mediated gene regulation and drives colon cancer in mice. Nature Genetics. 2017; 49(2):296-302. (view details in PubMed)
Kim KH*, Alver BH*, Lu P*, Wang X, Manchester HE, Wang W, Haswell JR, Park PJ, and Roberts CW. (*Co-first author) The SWI/SNF chromatin remodelling complex is required for maintenance of lineage specific enhancers. Nat Commun. 2017 Mar 6;8:14648. (view details in PubMed)
Vierbuchen T, Ling E, Cowley CJ, Couch CH, Wang X, Harmin DA, Roberts CWM, Greenberg ME. AP-1 Transcription Factors and the BAF Complex Mediate Signal-Dependent Enhancer Selection. Molecular Cell. 2017, 68(6):1067-1082. (view details in PubMed)
Helming KC*, Wang X*, Roberts CW. (*Co-first author) Vulnerabilities of Mutant SWI/SNF Complexes in Cancer. Cancer Cell. 2014, 26 (3):309-317. (view details in PubMed)
Wilson BG, Helming KC, Wang X, Kim Y, Vazquez F, Jagani Z, Hahn WC, Roberts CW. Residual complexes containing SMARCA2 (BRM) underlie the oncogenic drive of SMARCA4 (BRG1) mutation. Mol Cell Biol. 2014 Mar;34(6):1136-44. (view details in PubMed)
Helming KC, Wang X*, Wilson BG, Vazquez F, Haswell JR, Manchester HE, Kim Y, Kryukov GV, Ghandi M, Aguirre AJ, Jagani Z, Wang Z, Garraway LA, Hahn WC, Roberts CW. (*Co-first author) ARID1B is a specific vulnerability in ARID1A-mutant cancers. Nat Med. 2014, 20 (3):251-4. (view details in PubMed)
Wang X, Haswell JR, Roberts CW. Molecular Pathways: SWI/SNF (BAF) Complexes Are Frequently Mutated in Cancer--Mechanisms and Potential Therapeutic Insights. Clin Cancer Res. 2013, 20(1):21-7 (view details in PubMed)