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Aaron Monroy

Mentor: David L. Roman, PhD

Year Entered Into Program: 2008

PhD Institution: University of Iowa, 2013

Affiliations

  • Medicinal and Natural Products Chemistry

Research Description

G-protein coupled receptors (GPCRs) are among the most common targets for modern drug discovery. GPCRs are coupled to heterotrimeric G proteins consisting of α, β, and γ subunits. Activation of the receptor triggers the exchange of guanosine-diphosphate (GDP) for guanosine-triphosphate (GTP) ligand on the α-subunit (Gα). The α-subunit then disassociates from the β- and γ-subunits and either activates a pathway (Gαs) or inhibits a pathway (Gαo, z, i), depending on the nature of the GPCR. Regulators of G-protein signaling (RGS) proteins facilitate the termination of inhibitory G-protein signaling by increasing the Gα subunits’ intrinsic GTPase activity, rapidly facilitating the hydrolysis of GTP, and retuning the Gα subunit to the GDP-bound form. Our laboratory is interested on how environmentally induced oxidative stress effects these, and other, signaling proteins. The current hypothesis driving my research is that oxidative stress in cells form lipid peroxidation products, which can react with RGS proteins and inhibit their function, causing aberrant signaling. As a model for this process, I am using the reactive aldehyde 4-hydroxynonenol (4HNE) to probe potential regulatory sites on RGS4. Further research will include whole cell studies designed to investigate the expression and localization changes of RGS4 in response to oxidative stress and 4HNE modification.

Awards

  • Organizing Committee Board Member, 50th Annual MIKI Mtg, 2011
  • NIH T32 Pharmacological Sciences Training Grant, University of Iowa, 2009-2011
  • Recipient, FASEB / Minority Access to Research Careers Travel Award, 2011
  • Dolores Shockley Award, American Society for Pharmacology and Experimental Therapeutics National Meeting, 2011
  • Recipient, FASEB / Minority Access to Research Careers Travel Award, 2012
  • MNPC Graduate Student Travel Award, Gordon Research Conferences, 2012
  • Carl Strom Travel Award, Gordon Research Conferences, 2012
  • College of Pharmacy Dissertation Fellowship: Fellow, Jan 13 - May 13

Publications

  1. Roman, D.L., Blazer, L.L., Monroy, C.A. and Neubig, R.R.:  Alloseric inhibition of the regulator of G protein signaling-Galpha protein-protein interaction by CCG-4986. Molecular Pharmacology 78(3):360-365, 2010.  PMCID: PMC2939487

Research