Washburn Scores Grant to Advance Understanding of Cancer Therapy

Director of the Proteomics Center Michael Washburn, PhD, has been awarded a $1.5 million multiyear competitive grant by the National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health (NIH). Washburn was awarded the grant to further explore the mechanism of action of suberoylanilide hydroxamic acid (SAHA). This molecule inhibits enzymes called histone deacetylases (HDACs), which have been directly linked to cancer. SAHA is used in the treatment of certain lymphomas and is being evaluated in clinical trials for other cancers.

Specifically, SAHA inhibits the catalytic activity of HDAC enzymes. Inhibition of HDAC activity results in changes to gene expression that can block cell growth and increase cell death. Recent research suggests that SAHA has additional, noncatalytic effects that involve the HDAC protein network more broadly, thus suggesting other possible mechanisms of action. Washburn and his team hope to gain a deeper understanding of how SAHA achieves its pharmacological effects and provide a framework for the development of more specific and effective HDAC inhibitor therapies.

Washburn insists that this grant was possible only because of the quality of collaborative work at the Institute. Previous HDAC inhibitor studies by Stowers colleagues contributed to the breadth of knowledge that underlies his hypothesis that SAHA induces a dynamic rearrangement of an entire protein interaction network that plays a key role in how SAHA produces its pharmacological effects.

"We have collaborated with Jerry Workman, PhD, and his team for many years, and this project is the direct result of an excellent collaboration between Mihaela Sardiu, PhD, in the Proteomics Center and Karen Smith, PhD, formerly in the Workman group. Without Mihaela and Karen's efforts, this grant would not have been possible."