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Tansey, William, PhD

Researcher Profiles

Researcher Profiles

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William Tansey, Ph.D.

William Tansey, Ph.D.

Vanderbilt University School of Medicine

2016 Funding Recipient

Understanding how the oncoprotein transcription factor MYC features in the progression of myelodysplastic syndrome (MDS) to acute myeloid leukemia (AML).

Vanderbilt-Ingram Cancer Center MDS Research Consortium Award

PROJECT SUMMARY

Roughly one third of all patients suffering from myelodysplastic syndrome (MDS) will go on to develop AML, a type of leukemia that is difficult to treat and often fatal. The processes that drive progression of MDS to AML are largely unknown, but often involve two genes called BAP1 and ASXL1. Work in the Tansey laboratory has uncovered a molecular pathway that potentially connects BAP1 and ASXL1 to a third gene, MYC, which is well-known for its role in promoting tumor development. The goal of this project is to explore this molecular pathway, and in the process learn whether MYC contributes to AML development and whether MYC inhibitors could provide a way to reverse or slow down this deadly disease progression. In the last year, we have continued to characterize the cellular proteins that connect BAP1/ASXL1 to MYC and learned how they perturb the molecular functions of MYC. We have also tested the significance of this connection to tumorigenesis in mice, and are in the process of developing more sophisticated mouse model systems to explore the direct connection between BAP1 and MYC in MDS progression. Finally, we have accelerated efforts to drug MYC via the use of small molecules, and are making rapid progress towards our goal of targeting MYC in cancers, including AML.

PUBLICATIONS

Thomas LR, Foshage AM, Weissmiller AM, Popay TM, Grieb BC, Qualls SJ, Ng V, Carboneau B, Lorey S, Eischen CM, Tansey WP. Interaction of MYC with Host Cell Factor-1 is mediated by the evolutionarily-conserved Myc box IV motif. Oncogene. Nov 2, 2015. Epub ahead of print.

Thomas LR, Foshage AM, Weissmiller AM, Tansey WP. The MYC–WDR5 nexus and cancer. Cancer Research. 2015, 75: 4012–4015.

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