Mackenzie Spicer, PhD

Address: 2-505 BSBMackenzie Spicer - Dare to Discover photo
Phone: (319) 335-8330
Email: mackenzie-spicer@uiowa.edu

Mentor:  Rory A. Fisher, PhD

PhD Institution:  University of Iowa, 2022

Research Description

Molecular Biology and Signaling of RGS Proteins in Neuropsychiatric Disorders


The Fisher lab studies regulator of G-protein signaling (RGS) proteins, which are key negative regulators of G protein coupled receptor (GPCR) signaling by virtue of their GTPase-activating protein (GAP) activity toward G protein subunits. GPCR signaling activates a variety of specific second messenger systems that function to control a wide range of important physiological and pathophysiological processes.

Our lab has identified that a specific RGS protein, RGS6, plays a key role in modulating two key dopaminergic pathways in the brain central to the pathogenesis of both Parkinson’s disease (PD) and alcohol use disorders (AUDs).  We discovered that RGS6 is required for the survival of dopaminergic neurons in the substantia nigra pars compacta (SNc) region of the midbrain, and loss of RGS6 in mice results in late-age-onset SNc neurodegeneration and Parkinsonian-like motor dysfunction. Interestingly, RGS6 also promotes alcohol seeking and reward behaviors in young mice.  Our studies suggest that RGS6 functions in the nigrostriatal circuit to negatively regulate neuronal Gαi/o-coupled receptors implicated in PD, as well as in the mesolimbic circuit to control alcohol reward behaviors observed in AUDs.

My studies will interrogate the role of RGS6 in modulating dopaminergic neurotransmission in the mesolimbic circuit, and determine the mechanisms by which RGS6 in the VTA promotes dopamine transmission and alcohol seeking and reward behaviors.  From these studies, we seek to illuminate an entirely novel signaling pathway critical to dopamine transmission and neuronal activity whose signaling underlies reward and dependence behavior.

Awards

  • Pharmaceutical and Pharmacological Sciences Research Retreat, Poster Presentation Award, University of Iowa, 2022
  • University of Iowa Molecular Medicine Research Retreat Oral Presentation Award Recipient, 2020
  • Highlighted Trainee Award, Molecular Pharmacology Journal, 2020
  • University of Iowa Dare to Discover Campaign, 2020
  • University of Iowa Graduate College Summer Fellowship for Summer 2020
  • University of Iowa Three Minute Thesis (3MT) People's Choice Award Recipient, November 2019
  • University of Iowa Three Minute Thesis (3MT) Honorable Mention Award Recipient, November 2019
  • University of Iowa Three Minute Thesis (3MT) Finalist, November 2019
  • Poster Award Recipient, University of Iowa Pharmacology Biomedical Sciences Program, November 2019
  • Blue Ribbon Poster Award, ASPET Division for Molecular Pharmacology Program Committee, Experimental Biology Conference April 2019
  • Fellowship appointment on the Pharmacological Sciences Training Program (NIH T32 GM067795), University of Iowa, 2018-2020
  • University of Iowa Molecular Medicine Research Retreat Poster Session Award Recipient, 1st place, 2018

Publications

  1. Ahlers-Dannen KE*, Spicer MM*, and Fisher RA*.:  RGS proteins as critical modulators of motor function and their implications in Parkinson's disease. Mol Pharmacology 2020 Feb 3;mol.119.118836. doi: 10.1124/mol.119.118836. Online ahead of print. PMID: 32015009  *Denotes co-first authors
  2. Luo Z, Ahlers-Dannen KE, Spicer MM, Yang J, Alberico S, Stevens HE, Narayanan NS, Fisher RA.: Age-dependent nigral dopaminergic neurodegeneration and α-synuclein accumulation in RGS6-deficient mice.  JCI Insight 5(13):e126769, PMID: 31120439; PMCID: PMC6629243
  3. Yang J*, Ahlers-Dannen KE*, Spicer MM, Maity B, Stewart A, Koland JG, and Fisher RA.: RGS6 protein profiling reveals multi-isoformic expression in mouse tissues and a novel brain-specific isoform. In Preparation, 2020. *Denotes co-first authors
  4. Hart SL, Spicer MM, Wrynn TE, Chapman TL, Spivey KL, and Gall BG.:  Palatability and predator avoidance behavior of salamanders in response to the Virginia Opossum (Didelphis virginiana). American Midland Naturalist, 181(2), 245-258, 2019.
  5. Spicer MM, Stokes A, Chapman TL, Brodie ED. Jr, Brodie III ED, Gall BG.: An investigation into Tetrodotoxin (TTX) levels associated with the red dorsal spots in Eastern newt (Notophthalmus viridescens) efts and adults. J of Toxicology, 2018.  Article ID 9196865
  6. Spicer MM, Hart SL, Brighty SR, Gall BG.: Absence of visual discrimination by female Eastern newts during mate selection. Ethology Ecology & Evolution, 29(5):490-500, 2017.
  7. Hart SL, Spicer MM, and Gall BG.:  Clutch-level variation in predator avoidance behavior in wood frog (Lithobates sylvaticus) tadpoles. Proceedings of the Indiana Academy of Science. 126: 200-206, 2017.

Research