Dr. Jason Chesney
Email Jason Chesney
Phone Number: 502-852-3402
Baxter II Building, Suite 204E
Louisville, KY 40202
Area of Interest:Molecular Targets
Laboratory Personnel:Yalcin, Abdullah
Dr. Chesney conducted his graduate studies at the Picower Institute for Medical Research where he identified a novel isozyme of 6-phosphofructo-2-kinase (PFKFB3) that is essential for cancer cell growth. Dr. Chesney’s laboratory examines the metabolic properties of transformed cells and neoplastic tissues in order to identify key regulatory enzymes involved in neoplastic metabolism. His research group has established that several enzymes are essential for neoplastic metabolism, including transaldolase, transketolase, PFKFB3, lactate dehydrogenase, glutamate dehydrogenase and cytochrome c oxidase. Their approach is to suppress the activity of these metabolic regulators using a combination of siRNA silencing and genomic deletion and then to examine the effects on the metabolism, growth and survival of primary and transformed cells. Once regulatory enzymes have been validated as being selectively required for neoplastic cell growth or survival, then competitive inhibitors of the substrate-binding domains of these enzymes are identified via a combination of computational modeling and virtual screening. Candidate compounds are screened for competitive inhibitory properties against the targeted enzymes and then for cytostatic and cytotoxic effects on transformed cells grown in athymic mice. Using this approach, several PFKFB3 inhibitors have been identified that exhibit selective cytotoxic and cytostatic properties against tumors grown in mice. Pre-clinical studies are now underway to facilitate the initiation of phase I clinical trials examining this new class of chemotherapeutic agents in patients with leukemias and metastatic solid malignancies.