
William P. Tansey, Ph.D.
- Co-Leader, Genome Maintenance Research Program
- Ingram Professor of Cancer Research
- Professor of Cell and Developmental Biology
Phone
4140-A MRB 3, 465 21st Ave So.
Nashville, TN 37232-8240
William P. Tansey, Ph.D.
- Co-Leader, Genome Maintenance Research Program
- Ingram Professor of Cancer Research
- Professor of Cell and Developmental Biology
615-322-1993
william.p.tansey@vanderbilt.edu
4140-A MRB 3, 465 21st Ave So.
Nashville, TN 37232-8240
Research Program
Departments/Affiliations
Profile
Education
Research Emphasis
Cancer, chromatin, transcription, gene expression, cancer therapy
Research Description
Research Description: We study transcriptional regulation in normal and cancer cells. Research in the laboratory is focused squarely on understanding how the oncoprotein transcription factor MYC works and how it can be targeted for therapeutic effect in cancer cells.
The term “MYC” refers to a family of three related oncogenes that are broadly over-expressed in cancer and contribute to an estimated 100,000 cancer deaths annually in the United States alone. MYC proteins function as transcriptional regulators, controlling the expression of thousands of genes linked to cell growth, proliferation, metabolism, and genomic instability. MYC proteins are highly-validated but challenging drug targets for cancer therapy. Our work seeks to expose basic mechanisms of MYC action that can lead to new strategies to target MYC in the clinic. We study interactions of MYC with chromatin regulators in multiple cancer contexts, and collaborate to develop small molecule inhibitors of one particular chromatin-associated MYC co-factor, WDR5, and to explore their utility as anti-cancer agents.
Publications
- Moe KC, Maxwell JN, Wang J, Jones CA, Csaki GT, Florian AC, Romer AS, Bryant DL, Farone AL, Liu Q, Tansey WP, Weissmiller AM. The SWI/SNF ATPase BRG1 facilitates multiple pro-tumorigenic gene expression programs in SMARCB1-deficient cancer cells. Oncogenesis. 2022 Jun 6/1/2022; 11(1): 30. PMID: 35650187, PMCID: PMC9160003, PII: 10.1038/s41389-022-00406-6, DOI: 10.1038/s41389-022-00406-6, ISSN: 2157-9024.
- Metz EP, Wilder PJ, Popay TM, Wang J, Liu Q, Kalluchi A, Rowley MJ, Tansey WP, Rizzino A. Elevating SOX2 Downregulates MYC through a SOX2:MYC Signaling Axis and Induces a Slowly Cycling Proliferative State in Human Tumor Cells. Cancers (Basel). 2022 Apr 4/12/2022; 14(8): PMID: 35454854, PMCID: PMC9025961, PII: cancers14081946, DOI: 10.3390/cancers14081946, ISSN: 2072-6694.
- Florian AC, Woodley CM, Wang J, Grieb BC, Slota MJ, Guerrazzi K, Hsu CY, Matlock BK, Flaherty DK, Lorey SL, Fesik SW, Howard GC, Liu Q, Weissmiller AM, Tansey WP. Synergistic action of WDR5 and HDM2 inhibitors in SMARCB1-deficient cancer cells. NAR Cancer. 2022 Mar; 4(1): zcac007. PMID: 35252869, PMCID: PMC8892060, PII: zcac007, DOI: 10.1093/narcan/zcac007, ISSN: 2632-8674.
- Siladi AJ, Wang J, Florian AC, Thomas LR, Creighton JH, Matlock BK, Flaherty DK, Lorey SL, Howard GC, Fesik SW, Weissmiller AM, Liu Q, Tansey WP. WIN site inhibition disrupts a subset of WDR5 function. Sci Rep. 2022 Feb 2/3/2022; 12(1): 1848. PMID: 35115608, PMCID: PMC8813994, PII: 10.1038/s41598-022-05947-9, DOI: 10.1038/s41598-022-05947-9, ISSN: 2045-2322.
- Jones CA, Tansey WP, Weissmiller AM. Emerging Themes in Mechanisms of Tumorigenesis by SWI/SNF Subunit Mutation. Epigenet Insights. 2022; 15: 25168657221115656. PMID: 35911061, PMCID: PMC9329810, PII: 10.1177_25168657221115656, DOI: 10.1177/25168657221115656, ISSN: 2516-8657.
- Guarnaccia AD, Weissmiller AM, Tansey WP. Gene-specific quantification of nascent transcription following targeted degradation of endogenous proteins in cultured cells. STAR Protoc. 2021 Dec 12/17/2021; 2(4): 101000. PMID: 34917979, PMCID: PMC8669106, PII: S2666-1667(21)00706-1, DOI: 10.1016/j.xpro.2021.101000, ISSN: 2666-1667.
- Woodley CM, Romer AS, Wang J, Guarnaccia AD, Elion DL, Maxwell JN, Guerrazzi K, McCann TS, Popay TM, Matlock BK, Flaherty DK, Lorey SL, Liu Q, Tansey WP, Weissmiller AM. Multiple interactions of the oncoprotein transcription factor MYC with the SWI/SNF chromatin remodeler. Oncogene [print-electronic]. 2021 May; 40(20): 3593-609. PMID: 33931740, PMCID: PMC8141032, PII: 10.1038/s41388-021-01804-7, DOI: 10.1038/s41388-021-01804-7, ISSN: 1476-5594.
- Wolpaw AJ, Bayliss R, Büchel G, Dang CV, Eilers M, Gustafson WC, Hansen GM, Jura N, Knapp S, Lemmon MA, Levens D, Maris JM, Marmorstein R, Metallo SJ, Park JR, Penn LZ, Rape M, Roussel MF, Shokat KM, Tansey WP, Verba KA, Vos SM, Weiss WA, Wolf E, Mossé YP. Drugging the 'undruggable' MYCN oncogenic transcription factor: Overcoming previous obstacles to impact childhood cancers. Cancer Res [print-electronic]. 2021 Jan 1/28/2021; PMID: 33509943, PII: 0008-5472.CAN-20-3108, DOI: 10.1158/0008-5472.CAN-20-3108, ISSN: 1538-7445.
- Guarnaccia AD, Rose KL, Wang J, Zhao B, Popay TM, Wang CE, Guerrazzi K, Hill S, Woodley CM, Hansen TJ, Lorey SL, Shaw JG, Payne WG, Weissmiller AM, Olejniczak ET, Fesik SW, Liu Q, Tansey WP. Impact of WIN site inhibitor on the WDR5 interactome. Cell Rep. 2021 Jan 1/19/2021; 34(3): 108636. PMID: 33472061, PMCID: PMC7871196, PII: S2211-1247(20)31625-9, DOI: 10.1016/j.celrep.2020.108636, ISSN: 2211-1247.
- Popay TM, Wang J, Adams CM, Howard GC, Codreanu SG, Sherrod SD, McLean JA, Thomas LR, Lorey SL, Machida YJ, Weissmiller AM, Eischen CM, Liu Q, Tansey WP. MYC regulates ribosome biogenesis and mitochondrial gene expression programs through its interaction with host cell factor-1. Elife. 2021 Jan 1/8/2021; 10: PMID: 33416496, PMCID: PMC7793627, PII: 60191, DOI: 10.7554/eLife.60191, ISSN: 2050-084X.