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My postdoctoral research is focused on drug discovery. Using high-throughput screens, I am attempting to identify novel anti-cancer agents. One project, determined that flubendazole (I can finallysay the name!), a member of the benzimidazole family of drugs, possesses novel anti-cancer activity. Using molecular and biochemical techniques we have demonstrated that flubendazole was very effective at inducing apoptosis (cell death) of leukemia and myeloma cells. In addition, we demonstrated that this drug is potent in reducing tumors in mouse models. Mechanistically, flubendazole targets microtubules and inhibits tubulin polymerization and causes cell cycle arrest. Currently, we are working towards preparing flubendazole for clincal use.
I am also collaborating with fellow lab members. Together, we are investigating novel anti-cancer compounds. One such compound, tigecyline, has demonstrated activity against leukemia stem cells. In vivo studies, using the Dr. J. Dick model of leukemogenesis, has shown that this compound possesses great potential for eventual clinical application.
Currently, I have two projects on the go. The first is associated with a novel drug target. I am determining whether a cytoplasmic enzyme is associated with leukemogenesis. Preliminary results determined that this enzyme is elevated in leukemia cells including leukemia stem cells. The next steps are to determine the relationship between this enzyme and leukemogenesis and whether this enzyme is or can be targeted by chemotherapy. The second project involves combination screens. Here, I test the molecules of our chemical library with commonly used chemotherapy drugs to determine novel anti-cancer combination. In one screen, parthenolide, which is demonstrated to target leukemic stem cells and is in phase III clinical trials, was tested against our library. I have validated two of the several hits from this screen and am currently determining the mechanism by which these novel compounds combine with parthenolide to induce leukemic stem cell death.
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