Overview
Haystead, Timothy. Using chemical biology approaches to define novel drug targets for the treatment of hypertension, obesity, cancer, inflammatory and infectious disease.
Research Interests
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 Duke Appointments & Affiliations
Recent Scholarly Works
Development of domain-specific probes of Plasmodium falciparum heat shock protein 70-1.
Journal article Antimicrob Agents Chemother · August 5, 2026 In the malaria parasite Plasmodium falciparum, the essential chaperone PfHsp70-1 regulates proteostasis through protein folding, but its domain-specific functions remain poorly defined. The protein contains an N-terminal nucleotide-binding domain (NBD) and ... Full text Link to item CiteMapping the ATP-Binding Pockets of FLT3 and TAK1: A Structural Basis for Dual Inhibition by FLT3-Targeted Therapies.
Journal article ACS Chem Biol · June 19, 2026 Cutting edge protein kinase inhibitors are often plagued by unpredicted off target binding that can limit their therapeutic window, impacting clinical outcomes. However, such off-target binding may provide in vivo clinical evidence supporting therapeutic a ... Full text Link to item CitePharmacological inhibition of transforming growth factor-β activated kinase 1 (TAK1) prevents chemotherapy induced peripheral neuropathy (CIPN).
Journal article J Pain · June 2026 The development of chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting side effect of many neurotoxic chemotherapeutics where up to 30-40% of patients develop neuropathy. Traditionally, chemotherapeutics such as paclitaxel exert thei ... 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