Overview
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.
Current Appointments & Affiliations
Recent Publications
Selective targeting of Plasmodium falciparum Hsp90 disrupts the 26S proteasome.
Journal Article Cell Chem Biol · April 18, 2024 The molecular chaperone heat shock protein 90 (Hsp90) has an essential but largely undefined role in maintaining proteostasis in Plasmodium falciparum, the most lethal malaria parasite. Herein, we identify BX-2819 and XL888 as potent P. falciparum (Pf)Hsp9 ... Full text Link to item CiteTAK1 inhibition leads to RIPK1-dependent apoptosis in immune-activated cancers.
Journal Article Cell Death Dis · April 17, 2024 Poor survival and lack of treatment response in glioblastoma (GBM) is attributed to the persistence of glioma stem cells (GSCs). To identify novel therapeutic approaches, we performed CRISPR/Cas9 knockout screens and discovered TGFβ activated kinase (TAK1) ... Full text Link to item CiteTargeting Borrelia burgdorferi HtpG with a berserker molecule, a strategy for anti-microbial development.
Journal Article Cell Chem Biol · March 21, 2024 Conventional antimicrobial discovery relies on targeting essential enzymes in pathogenic organisms, contributing to a paucity of new antibiotics to address resistant strains. Here, by targeting a non-essential enzyme, Borrelia burgdorferi HtpG, to deliver ... Full text Link to item CiteRecent Grants
Chemical Biology Strategies to Resolve Plasmodium Heat Shock Protein Function
ResearchCo Investigator · Awarded by National Institute of Allergy and Infectious Diseases · 2023 - 2028Development of Diagnostic/Therapeutic Agents Targeting Borrelia burgdorferi HtpG
ResearchPrincipal Investigator · Awarded by Department of Defense · 2024 - 2027Development of an oral targeted drug for treatment of bartonelloses
ResearchPrincipal Investigator · Awarded by Steven & Alexandra Cohen Foundation · 2021 - 2026View All Grants