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Mentor: David Roman, PhD
Undergraduate Institution: Grinnell College, BA
Year Entered Into Program: 2010
PhD Institution: University of Iowa, 2015
Regulators of G Protein Signaling (RGS) proteins modulate the magnitude and duration of downstream signaling through G protein-coupled receptors (GPCRs) by binding to and accelerating the deactivation of Gα proteins, the canonical transducers of GPCR signaling. RGS proteins are vital for a vast array of physiological processes, but their activity also contributes to the pathophysiology of Parkinson’s disease and cancer and has been linked to depression, schizophrenia, and diabetes. Animal and cell RGSknockout studies in models of these diseases strongly suggest potential therapeutic indications for RGS inhibitors. To date, the only small molecule inhibitors that have been discovered are redox-sensitive covalent cysteine modifiers, and these molecular probes are unsuitable for clinical application. My research in the Roman lab is focused on leveraging the known activity and subtype specificity of these RGS inhibitors coupled with structural differences in RGS proteins to develop lead candidates more suitable for drug design.
Vermeer, L.M.,*, Higgins, C.A.*, Roman, D.L., Doorn, J.A.: Real-Time Monitoring of Tyrosine Hydroxylase Activity Using a Plate Reader Assay. Anal Biochem 432:11-15, 2013. PMCID: PMC3579528 [Available on 2014/1/1]
Higgins, C.A.*, Vermeer, L.M.*, Doorn, J.A., Roman, D.L.: Expression and Purification of Recombinant Human Tyrosine Hydroxylase as a Fusion Protein in Escherichia coli. Protein Expr Purif 84:219-223, 2012. PMCID: PMC3525113 [Available on 2013/8/1]
Cesa, L.C., Higgins, C.A., Sando, S.R., Kuo, D.W. and Levandoski, M.M.: Specificity Determinants of Allosteric Modulation in the Neuronal Nicotinic Acetylcholine Receptor: A Fine Line between Inhibition and Potentiation. Mol Pharmacol 81:239-249, 2011. PMCID: PMC3263947
*indicates shared first authorship
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