Julissa M. Molina-Vega is a junior at Macalester College in St. Paul, MN, majoring in Biochemistry and minoring in Chemistry. Her research interests include understanding signal transduction pathways that control cell survival and growth, the process of cancer invasion and metastasis, and the interactions between the host immune system and tumor cells and use the knowledge to develop more effective treatment therapies. Ms. Molina-Vega plans on pursuing a M.D./Ph.D. dual degree with her Ph.D. in Cancer Biology.
My dream is to conduct translational research that will improve human health and further develop novel approaches for targeted cancer treatment. At the same time, I hope to inspire other young women of color interested in science and medicine and in turn build a diverse scientific community that empowers disadvantaged students by providing access to research and physician shadowing opportunities.
Eicosanoid Regulation of the Nuclear Pore Complex in Breast Cancer
Abstract: Cytochrome P450 (CYP) enzymes are known to synthesize various endogenous eicosanoids such as epoxyeicosatrienoic acids (EETs) that have been demonstrated to promote cancer cell proliferation1. CYP3A4 is an arachidonic acid epoxygenase enzyme localized to perinuclear mitochondria in breast cancer cells and its knockdown activates AMPK, promotes autophagy, and prevents mammary tumor formation2. The diabetes drug metformin was recently discovered to inhibit CYP3A4-mediated EET biosynthesis. Unexpectedly, CYP3A4 knockdown and inhibition of EET biosynthesis by CYP3A4 was discovered to inhibit RagC localization to the nucleus, in part, due to modulation of the the nuclear pore complex (NPC)3 . N1-hexyl-N5-benzyl-biguanide (HBB) is a novel metformin-like compound that binds to and inhibits CYP3A4 with higher affinity, thereby serving as a chemical probe of the roles of EETs in breast cancer. HBB restrains transport of 70 kDa through the NPC in MCF-7 and T47D cell lines. HBB also reduced nuclear localization of RagC and ERα. Restricting nuclear passage of RagC prevents it from gaining its GDP-bound state necessary to activate mTOR3 and reducing translocation of ERα blocks its effect on cell proliferation, thereby inhibiting tumor growth. These results suggest that HBB can be utilized to inhibit growth of estrogen receptor-positive breast cancer cells by inhibiting passage of macromolecules through the NPC.
Dr. David Potter is an Associate Professor in the Department of Medicine, Division of Hematology, Oncology, and Transplantation and a Faculty member in the Microbiology, Immunology and Cancer Biology Ph.D. Graduate Program at the University of Minnesota. After completing his B.S. in Biology at M.I.T., Dr. Potter received M.D. and Ph.D. degrees from Johns Hopkins University. He trained in Internal Medicine at Stanford University Medical Center and in Hematology and Oncology at Tufts-New England Medical Center, and completed postdoctoral training at the M.I.T. Center for Cancer Research. In 2006, he became a member of the Breast Cancer Program at the Masonic Cancer Center. His research interests include the role of cytochrome P450 enzymes in breast cancer progression, development of chemical probes to target the electron transport chain in breast cancer, and translational development of new strategies for hormone therapy resistant breast cancer.