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.
Education and Training
- University of Dundee (Scotland), Ph.D. 1988
Selected Grants and Awards
- Targeting Borrelia specific immune cell populations in vivo through expression of ectopically expressed Hsp90
- Oncogenic Signaling Networks
- Improving the Oral Bioavailability and In vivo Efficacy of the TAK 1 Inhibitor, Takinib.
- Interdisciplinary Training Program in Lung Disease
- Improving the Oral Bioavailability and in vivo efficacy of the TAK 1 inhibitor, Takinib.
- Organization and Function of Cellular Structure
- Pharmacological Sciences Training Program
- Co-crystalization of inducible Heat shock Protein 70 with the inhibitor HS-72 and structural analogs.
- Pharmacology Industry Internships for Ph.D. Students
- A novel strategy to see and treat breast cancer: translation to intra-operative breast margin assessment
- Development of Tethered Hsp90 Inhibitors Carrying Radiolabelled Probes to Specifically Descriminate and Kill Malignant
- Discovery of novel liver host targets for malaria treatment
- Literature search of clinical trials studies on Hsp90 inhibitors
- Co-crystallization of Hsp70i and the inhibitor HS-72
- Targeting the synthetic essential kinases of breast cancers
- Preclinical Development of Novel HSP90 Inhibitors...
- The Duke Multidisciplinary Training Program in Pediatric Lung Disease
- Discovery and development of broad spectrum anti-flaviviral drugs
- A Novel Method to Stop HIV Replication: Inhibition of the Human Purinome
- Molecular mechanisms of chemoresistance in breast cancer
- Calcium desensitization in Smooth Muscle.
- Maturation of Normal & Sensitized Airway Contractility
- Proteome Mining as a Predictive Tool of Drug Toxicity
- G Protein Involvement in Oncogenesis and Metastasis
- Pseudomonas invasion and the role of caveolin-2
- Regulation of smooth muscle-myosin phosphatase 1 kinase
- Protein Phosphatase 1 Regulation by Multiple Subunits
- Graduate Training in Pharmalogical Sciences
- Proteomic/Genetic Approaches to Monoamine Transporters
- Activation of critical gene sets for spinal axon repair