Shwu-Yuan Wu, Ph.D. Assistant Professor School Medical School Department Harold C. Simmons Comprehensive Cancer Center | Biochemistry Biography I am a Research Assistant Professor in the Chiang lab. My research has been focused on transcription mechanisms since my graduate studies and postdoc straining with Dr. Robert G. Roeder at Rockefeller University. In Dr. Chiang’s laboratory, I expanded the purification and reconstitution of the human general transcription machinery and general cofactors, first initiated in the Roeder Lab, with bacterially expressed recombinant human proteins (TFIIA, TFIIB, TBP, TFIIE, TFIIF, PC4) and with FLAG-tagged multiprotein complexes (TFIID, TFIIH, non-phosphorylated or hyper-phosphorylated RNA polymerase II, and different forms of Mediator complexes) purified from human HeLa cells expressing an epitope-tagged subunit of a multiprotein complex. The availability of this reconstituted transcription system with DNA or chromatin templates allows me to define the mechanisms of eukaryotic transcription regulated by different transcriptional regulators, e.g., p53, activator protein-1 (AP-1), and human papillomavirus (HPV)-encoded E2 proteins. My recent establishment of in vitro modification assays with recombinant human enzymes for phosphorylation, acetylation, methylation, sumoylation, and ubiquitination studies expands a new line of research for defining the complexity of gene regulation involving chromatin and post-translational modification. I also conduct cell-based assays with both gain- and loss-of-function approaches to verify and discover new transcription mechanisms in living cells. Recently, I have employed genome-wide ChIP-seq/CUT&RUN and RNA-seq/PRO-seq approaches to define the functional roles of BRD4 protein isoforms and their transcriptional coregulators in different types of breast cancer cells and HPV-containing keratinocytes. I am also applying proteomics to identify protein-protein interactomes and drug targets. Education Graduate School Yang-Ming Medical College - Ch (1986), Biochemistry Graduate School University of Rochester (1993), Biochemistry Research Interest Chromatin and Epigenetics Human Papillomaviruses p53 Tumor Supressor Protein Post-Translational Modifications Transcription and Gene Regulation Publications Featured Publications IDR-targeting compounds suppress HPV genome replication via disruption of phospho-BRD4 association with DNA damage response factors. Wu SY, Lai HT, Sanjib Banerjee N, Ma Z, Santana JF, Wei S, Liu X, Zhang M, Zhan J, Chen H, Posner B, Chen Y, Price DH, Chow LT, Zhou J, Chiang CM, Mol Cell 2023 Dec The matrix protein of respiratory syncytial virus suppresses interferon signaling via RACK1 association. Cao J, Shi M, Zhu L, Li X, Li A, Wu SY, Chiang CM, Zhang Y, J Virol 2023 Sep e0074723 Direct interaction with the BRD4 carboxyl-terminal motif (CTM) and TopBP1 is required for human papillomavirus 16 E2 association with mitotic chromatin and plasmid segregation function. Prabhakar AT, James CD, Fontan CT, Otoa R, Wang X, Bristol ML, Yeager C, Hill RD, Dubey A, Wu SY, Chiang CM, Morgan IM, J Virol 2023 Sep e0078223 EGFR ligand shifts the role of EGFR from oncogene to tumour suppressor in EGFR-amplified glioblastoma by suppressing invasion through BIN3 upregulation. Guo G, Gong K, Beckley N, Zhang Y, Yang X, Chkheidze R, Hatanpaa KJ, Garzon-Muvdi T, Koduru P, Nayab A, Jenks J, Sathe AA, Liu Y, Xing C, Wu SY, Chiang CM, Mukherjee B, Burma S, Wohlfeld B, Patel T, Mickey B, Abdullah K, Youssef M, Pan E, Gerber DE, Tian S, Sarkaria JN, McBrayer SK, Zhao D, Habib AA, Nat Cell Biol 2022 Aug 24 8 1291-1305 Targeting ESR1 mutation-Induced transcriptional addiction in breast cancer with BET inhibition. Udden SN, Wang Q, Kumar S, Malladi VS, Wu SY, Wei S, Posner BA, Geboers S, Williams NS, Liu YL, Sharma JK, Mani RS, Malladi S, Parra K, Hofstad M, Raj GV, Larios JM, Jagsi R, Wicha MS, Park BH, Gupta GP, Chinnaiyan AM, Chiang CM, Alluri PG, JCI Insight 2022 Jul Conditional Human BRD4 Knock-In Transgenic Mouse Genotyping and Protein Isoform Detection. Lewis MP, Wu SY, Chiang CM, Bio Protoc 2022 Apr 12 7 Discovery, X-ray Crystallography, and Anti-inflammatory Activity of Bromodomain-containing Protein 4 (BRD4) BD1 Inhibitors Targeting a Distinct New Binding Site. Liu Z, Li Y, Chen H, Lai HT, Wang P, Wu SY, Wold EA, Leonard PG, Joseph S, Hu H, Chiang CM, Brasier AR, Tian B, Zhou J, J Med Chem 2022 Jan BRD4 inhibition and FXR activation, individually beneficial in cholestasis, are antagonistic in combination. Jung H, Chen J, Hu X, Sun H, Wu SY, Chiang CM, Kemper B, Chen LF, Kemper J, JCI Insight 2020 Dec Blood-based biomarkers of human papillomavirus-associated cancers: A systematic review and meta-analysis. Balachandra S, Kusin SB, Lee R, Blackwell JM, Tiro JA, Cowell LG, Chiang CM, Wu SY, Varma S, Rivera EL, Mayo HG, Ding L, Sumer BD, Lea JS, Bagrodia A, Farkas LM, Wang R, Fakhry C, Dahlstrom KR, Sturgis EM, Day AT, Cancer 2020 Dec Opposing Functions of BRD4 Isoforms in Breast Cancer. Wu SY, Lee CF, Lai HT, Yu CT, Lee JE, Zuo H, Tsai SY, Tsai MJ, Ge K, Wan Y, Chiang CM, Mol Cell 2020 06 78 6 1114-1132.e10 Results 1-10 of 58 1 2 3 4 5 Next Last Honors & Awards Postdoctoral FellowAaron Diamond Foundation (1995) Elon Huntington Hooker Graduate FellowshipUniversity of Rochester (1993) Professional Associations/Affiliations Case Western Reserve University, Cleveland, Ohio (2000-2007) Rockefeller University, New York, New York (1993-1995) University of Illinois at Urbana-Champaign, Urbana, Illinois (1995-2000) University of Rochester, Rochester, New York (1988-1993) University of Texas Southwestern Medical Center, Dallas, Texas (2007)
