Positions

Overview

  • My lab's overall research goal is to understand and investigate the cellular and immunological mechanisms underlying the initiation and progression of synucleinopathy disorders. Specifically, my lab research focuses on how the protein alpha-synuclein contributes to microglial activation, peripheral immune cell infiltration, and subsequent activation of the immune response in Parkinson disease (PD) and Multiple System Atrophy (MSA) models. In the lab we work with multiple immune cell types, including myeloid cell subsets and T cells to pursue research regarding these mechanisms. Therapeutic strategies targeting and blocking immune system activation have been neuroprotective, however, differentially targeting immune cell subsets in the central nervous system (CNS), specifically microglia, without undesirable effects on extra-CNS immunity has been a challenge. By combining transgenic animals with an alpha-synuclein viral models of PD and MSA to study the role of immune cells subsets, we aim to dissect mechanisms of immune-mediated disease pathogenesis in synucleinopathy disorders.
  • Selected Publications

    Academic Article

    Year Title Altmetric
    2018 Glial GLP1R: A novel neuroprotector?Movement Disorders.  33:1877. 2018
    2018 Targeting of the class II transactivator attenuates inflammation and neurodegeneration in an alpha-synuclein model of Parkinson's diseaseJournal of Neuroinflammation.  15. 2018
    2018 Peripheral monocyte entry is required for alpha-Synuclein induced inflammation and Neurodegeneration in a model of Parkinson diseaseExperimental Neurology.  300:179-187. 2018
    2017 α-Synuclein fibrils recruit peripheral immune cells in the rat brain prior to neurodegenerationAsian Philosophy.  5:85. 2017
    2016 How can rAAV-α-synuclein and the fibril α-synuclein models advance our understanding of Parkinson's disease?Journal of Neurochemistry.  131-155. 2016
    2016 The Metabotropic Glutamate Receptor 4 Positive Allosteric Modulator ADX88178 Inhibits Inflammatory Responses in Primary MicrogliaJournal of Neuroimmune Pharmacology.  11:231-237. 2016
    2016 Inhibition of the JAK/STAT pathway protects against α-synuclein-induced neuroinflammation and dopaminergic neurodegenerationJournal of Neuroscience.  36:5144-5159. 2016
    2016 MicroRNA-155 regulates alpha-synuclein-induced inflammatory responses in models of Parkinson diseaseJournal of Neuroscience.  36:2383-2390. 2016
    2015 Fractalkine signaling regulates the inflammatory response in an α-synuclein model of Parkinson diseasePLoS ONE.  10. 2015
    2014 Fiber-modified adenovirus for central nervous system Parkinson's disease gene therapyViruses.  6:3293-3310. 2014
    2014 Monocytes and Parkinson's disease: Invaders from outside?Movement Disorders.  29:1242. 2014
    2013 Isolation of murine postnatal brain microglia for phenotypic characterization using magnetic cell separation technologyMethods in Molecular Biology.  1041:33-39. 2013
    2013 MHCII is required for α-Synuclein-induced activation of microglia, CD4 T cell proliferation, and dopaminergic neurodegenerationJournal of Neuroscience.  33:9592-9600. 2013
    2012 The gamma chain subunit of Fc receptors is required for alpha-synuclein-induced pro-inflammatory signaling in microgliaJournal of Neuroinflammation.  9. 2012
    2012 Regulation of microglia effector functions by tumor necrosis factor signalingGlia.  60:189-202. 2012
    2011 Delayed dominant-negative TNF gene therapy halts progressive loss of nigral dopaminergic neurons in a rat model of parkinson's diseaseMolecular Therapy.  19:46-52. 2011
    2009 Inhibition of soluble TNF signaling in a mouse model of Alzheimer's disease prevents pre-plaque amyloid-associated neuropathologyNeurobiology of Disease.  34:163-177. 2009
    2008 Regulator of G-protein signaling 10 promotes dopaminergic neuron survival via regulation of the microglial inflammatory responseJournal of Neuroscience.  28:8517-8528. 2008
    2008 Effects of estrogen receptor agonists on regulation of the inflammatory response in astrocytes from young adult and middle-aged female ratsJournal of Neuroimmunology.  195:47-59. 2008

    Research Overview

  • Neuroimmunology, Neuroscience, Immunology, Neurodegeneration, Aging,
  • Investigator On

  • Interactions of Gut Microbiome, Genetic Susceptibility and Environmental Factors in Parkinson's Disease  awarded by DOD - Department of Defense 2018 - 2022
  • Border-Associated Macrophages in an Alpha-Synuclein Overabundance Model of Parkinson Disease  awarded by National Institute of Neurological Disorders and Stroke/NIH/DHHS 2018 - 2021
  • Role of T cells in an Alpha-Synuclein Mediated Mouse Model of Parkinson Disease  awarded by National Institute of Neurological Disorders and Stroke/NIH/DHHS 2018 - 2021
  • Advancing PINK1 KO Rat Animal Models of PD  awarded by Fox (Michael J.) Foundation for Parkinson's Research 2017 - 2019
  • Mechanisms of LRRK2 Mediated Neurotoxicity  awarded by National Institute of Neurological Disorders and Stroke/NIH/DHHS 2016 - 2019
  • Innate and Adaptive Immunity in Parkinson Disease  awarded by National Institute of Neurological Disorders and Stroke/NIH/DHHS 2015 - 2018
  • Innate and Adaptive Immunity in Parkinson Disease - Project 1: PD-Linked Susceptibilities in Myeloid-Cell CNS Infiltration  awarded by National Institute of Neurological Disorders and Stroke/NIH/DHHS 2015 - 2018
  • Validation of the Class II MHC Transactivator (CIITA) in Models of PD  awarded by Fox (Michael J.) Foundation for Parkinson's Research 2014 - 2016
  • Role of MHC II Proteins in Parkinson's Related Inflammation  awarded by RJG FOUNDATION 2011 - 2014
  • Targeting the JAK/STAT Pathway in the Treatment of Parkinson's Disease  awarded by Fox (Michael J.) Foundation for Parkinson's Research 2012 - 2014
  • Education And Training

  • Doctor of Philosophy in Biological and Biomedical Sciences, University of Texas System : Southwestern Medical Center at Dallas 2010
  • Full Name

  • Ashley Harms