Haystead, Timothy. Using chemical biology approaches to define novel drug targets for the treatment of hypertension, obesity, cancer, inflammatory and infectious disease.
The major focus of my laboratory is the discovery and development of novel small molecule inhibitors targeting purine-utilizing proteins involved in various aspects of human disease. Specific targets of interest include heat shock protein 90 (Hsp90), heat shock protein 70 (Hsp70), fatty acid synthase, acetyl CoA Carboxylase, DAPK3 (ZIPK), PIM kinases, dengue fever non-structural protein 5 (NS5) and TAK1 (haysteadlab.com). Hsp90, Hsp70 and fatty acid synthase all have cancer and antiviral therapeutic indications and we are actively developing a series molecules specifically targeting these proteins that were scratch discovered in our laboratory. We have also developed a series of novel imaging molecules based on our Hsp90 inhibitor series that have utility as both diagnostics and potentially curative strategies for a number human cancers and viral infections. Our DAPK(ZIPK) and PIMK inhibitors have shown indications as anti-hypertensive agents as well as having utility in preventing reperfusion injury after stroke. Our TAK1 inhibitor program (discovered with the Derbyshire Laboratory, Department of Chemistry, Duke) has defined a highly potent and selective inhibitor of TAK1 kinase an important protein kinases thought to mediate the actions of proinflammatory cytokines such as TNFa, IL1 and TGFb. The foundations of these programs are based on the development a chemoproteomic strategy utilizing affinity methods combined with in house organic synthetic chemistry.