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Mentor: Michael Henry, PhD
Year Entered Into Program: 2007 (MSTP) 2009 (PhD Program)
PhD Institution: University of Iowa, 2015 (MD, PhD)
Prostate cancer is the most common visceral cancer affecting males of the U.S. While radical prostatectomy is often effective for local disease, advanced disease is often treated with androgen deprivation. Unfortunately, this therapy is considered mostly palliative as recurrence often occurs with a hormone refractory phenotype that is highly aggressive. It is thought that neuroendocrine (NE) cells may represent a highly malignant population involved in hormone refractory disease. The Henry lab has developed a cell line that we believe mimics NE disease, and we have utilized it to create microarray data profiling the NE phenotype and comparing it to its more epithelial parental line to determine what molecular changes occur for neuroendocrine differentiation (NED). Our work is focused on elucidating the role of the GABA B receptor, a metabotropic G-protein coupled receptor with a documented role in other visceral cancers. We believe that modulation of this receptor has important downstream effects in the cancer’s ability to metastasize due to its ability to affect the metabolic profile of the cell. Furthermore, we’re profiling signaling proteins such as FOXA2 that may play a role in the regulation of GABA B receptor expression. The long-term goal for the work is to identify novel therapeutics that can be used as a combinatorial agent with current generation androgen therapies to reduce the occurrence of hormone refractory disease.
Esser, A.K1, Miller, M.R1, Huang, Q., Meier, M.M., Beltran, D., Stipp, C.S., Campbell, K.P., Lynch, C.F., Smith, B.J., Cohen, M.B., Henry, M.D.: Loss of LARGE2 Disrupts Functional Glycosylation of a-Dystroglycan in Prostate Cancer. J Biol Chem 288(4):2132-2142, 2013. PMCID: PMC3554886 [Available on 2014/1/25] 1These authors contributed equally to this work.
Corbin, B.D., Seeley, E.H., Raab, A., Feldmann, J., Miller, M.R., Torres, V.J., Anderson, K.L., Dattilo, B.M., Dunman, P.M., Gerads, R., Caprioli, R.M., Nacken, W., Chazin, W.J., Skaar, E.P.: Metal chelation and inhibition of bacterial growth in tissue abscesses. Science 319(5865):962-965, 2008. PMID: 18276893
Bunick, C.G., Miller, M.R., Fuller, B.E., Fanning, E., Chazin, W.J.: Biochemical and structural domain analysis of xeroderma pigmentosum complementation group C protein. Biochemistry 45(50):14965-79, 2006. PMCID: PMC2579963
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