Nazarius Lamango, Ph.D.Professor Medicinal Chemistry
LOCATION: Tallahassee, Science Research Room 209G
BiosketchThe research focuses on finding the molecular hallmarks of some of the most difficult-to-treat cancers with the potential for diagnostic and therapeutic applications. Polyisoprenylated methylated protein methyl esterase (PMPMEase, human carboxylesterase 1, hCE1) is a key enzyme responsible for the oncogenic transformation of proteins in some key growth signaling pathways [1-3]. PMPMEase inhibition induces the death of cancer cells [1, 3, 4], suggesting that its hyperactivity possibly promotes cancer growth. Since PMPMEase is a ubiquitous eukaryotic protein, it may contribute to cases of a wide range of cancer types. The working hypothesis is therefore that PMPMEase hyperactivity promotes cancer progression and that inhibiting any excessive activities to normal levels constitutes a viable therapeutic approach. To meet the goal for effective therapeutic management, a three-pronged research strategy involving (1) determination of PMPMEase expression in tumors relative to normal tissues, (2) design and synthesis of small molecule inhibitors of PMPMEase or disruptors of polyisoprenylated protein function and (3) biochemical evaluation and in vivo testing of the compounds for anti-tumor activity. The ultimate goals are to obtain novel and effective targeted anticancer therapies and a companion diagnostic method for identifying patients likely to benefit from it. The patents obtained so far for this work embody this basic approach. Another aspect of the research is to identify naturally occurring substances in foods that inhibit PMPMEase and cell proliferation that could serve to explain cancer initiation and/or progression mechanisms as well as be used as nutraceuticals to prevent cancers [3, 5].