Positions

Overview

  • Biographical Sketch

    The goal of the lab is to halt the progression of synucleinopathies including Parkinson's Disease, and Lewy Body Dementia, the second most common cognitive disorder after Alzheimer's Disease. The lab uses mouse models to determine the role of genes implicated in these neurodegenerative diseases on formation of alpha-synuclein inclusions. We also want to determine how these aggregates cause defects in neuron function, as well as motor and cognitive phenotypes. Techniques used in the lab range from super-resolution microscopy in mouse and human brain tissues, live cell imaging, protein purification and biochemistry, and behavior. Dr. Volpicelli-Daley is also dedicated to ensuring the success of future scientists and physicians.

    • Selected Publications

    Academic Article

    Year Title Altmetric
    2021 Alpha-synuclein alters the faecal viromes of rats in a gut-initiated model of Parkinson’s disease.  Communications Biology.  4. 2021
    2021 Inhibition of LRRK2 kinase activity promotes anterograde axonal transport and presynaptic targeting of α-synuclein.  Acta Neuropathologica Communications.  9. 2021
    2021 Corrigendum to “α-Synuclein fibril-induced inclusion spread in rats and mice correlates with dopaminergic Neurodegeneration” [Neurobiol. Dis., Volume 105 (2017) Article 84, 98](S0969996117301201)(10.1016/j.nbd.2017.05.014).  Neurobiology of Disease.  159. 2021
    2021 Erratum: LRRK2 Antisense Oligonucleotides Ameliorate α-Synuclein Inclusion Formation in a Parkinson's Disease Mouse Model (Molecular Therapy - Nucleic Acids (2017) 8 (508–519), (S2162253117302287), (10.1016/j.omtn.2017.08.002)).  Molecular Therapy : Nucleic Acids.  25:152-154. 2021
    2021 Erratum: LRRK2 Antisense Oligonucleotides Ameliorate α-Synuclein Inclusion Formation in a Parkinson's Disease Mouse Model (Molecular Therapy - Nucleic Acids (2017) 8 (508–519), (S2162253117302287), (10.1016/j.omtn.2017.08.002)).  Molecular Therapy : Nucleic Acids.  24:1051-1053. 2021
    2021 Molecular Mechanisms Underlying Synaptic and Axon Degeneration in Parkinson’s Disease.  Frontiers in Cellular Neuroscience.  15. 2021
    2021 Erratum: Definingα-synuclein species responsible for Parkinson's disease phenotypes in mice (J Biol Chem (2019) 294:27 (10392-10406) DOI: 10.1074/jbc.RA119.007743).  Journal of Biological Chemistry.  295:1142. 2021
    2021 Templated α-synuclein inclusion formation is independent of endogenous tau.  eNeuro.  8. 2021
    2020 Multiplicity of α-synuclein aggregated species and their possible roles in disease.  International Journal of Molecular Sciences.  21:1-27. 2020
    2020 Initiation and propagation of α-synuclein aggregation in the nervous system.  Molecular Neurodegeneration.  15. 2020
    2020 Gut-seeded α-synuclein fibrils promote gut dysfunction and brain pathology specifically in aged mice.  Nature Neuroscience.  23:327-336. 2020
    2020 Behavioral defects associated with amygdala and cortical dysfunction in mice with seeded α-synuclein inclusions.  Neurobiology of Disease.  134. 2020
    2020 Erratum: Definingα-synuclein species responsible for Parkinson's disease phenotypes in mice (Journal of Biological Chemistry (2019) 294 (10392–10406) DOI: 10.1074/jbc.RA119.007743).  Journal of Biological Chemistry.  295:1142. 2020
    2019 Hsp110 mitigates α-synuclein pathology in vivo 2019
    2019 Neuronal vulnerability in Parkinson disease: Should the focus be on axons and synaptic terminals?.  Movement Disorders.  34:1406-1422. 2019
    2019 Defining α-synuclein species responsible for Parkinson's disease phenotypes in mice.  Journal of Biological Chemistry.  294:10392-10406. 2019
    2019 Generation of alpha-synuclein preformed fibrils from monomers and use in vivo.  Journal of Visualized Experiments.  2019. 2019
    2019 Pα-syn* mitotoxicity is linked to MAPK activation and involves tau phosphorylation and aggregation at the mitochondria.  Neurobiology of Disease.  124:248-262. 2019
    2019 Assays for neuronal defects caused by early formation of α-synuclein inclusions in primary cultured neurons.  Methods in Molecular Biology.  1948:1-14. 2019
    2018 14-3-3 proteins reduce cell-to-cell transfer and propagation of pathogenic α-synuclein 2018
    2018 Sensitivity and specificity of phospho-Ser129 α-synuclein monoclonal antibodies.  Journal of Comparative Neurology.  526:1978-1990. 2018
    2018 α-Synuclein fibril-induced paradoxical structural and functional defects in hippocampal neurons.  Acta Neuropathologica Communications.  6:35. 2018
    2018 Best practices for generating and using alpha-synuclein pre-formed fibrils to model Parkinson's disease in rodents.  Journal of Parkinson's Disease.  8:303-322. 2018
    2018 Editorial: Pathogenic templating proteins in Neurodegenerative Disease.  Neurobiology of Disease.  109:175-177. 2018
    2018 Identification of a highly neurotoxic α-synuclein species inducing mitochondrial damage and mitophagy in Parkinson’s disease 2018
    2017 LRRK2 Antisense Oligonucleotides Ameliorate α-Synuclein Inclusion Formation in a Parkinson's Disease Mouse Model.  Molecular Therapy : Nucleic Acids.  8:508-519. 2017
    2017 Effects of α-synuclein on axonal transport.  Neurobiology of Disease.  105:321-327. 2017
    2017 α-Synuclein fibril-induced inclusion spread in rats and mice correlates with dopaminergic Neurodegeneration.  Neurobiology of Disease.  105:84-98. 2017
    2017 Trehalose does not improve neuronal survival on exposure to alpha-synuclein pre-formed fibrils.  Redox Biology.  11:429-437. 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 G2019s-LRRK2 expression augments α-synuclein sequestration into inclusions in neurons 2016
    2016 MicroRNA-155 regulates alpha-synuclein-induced inflammatory responses in models of Parkinson disease 2016
    2016 Invisible Killers.  Movement Disorders.  31:44-44. 2016
    2015 Trophic factors for Parkinson's disease: To live or let die.  Movement Disorders.  30:1715-1724. 2015
    2015 Transforming growth factor beta (TGF-β) is a muscle biomarker of disease progression in ALS and correlates with smad expression.  PLoS ONE.  10. 2015
    2015 Leucine-rich repeat kinase 2 (LRRK2) pharmacological inhibition abates α-synuclein gene-induced neurodegeneration.  Journal of Biological Chemistry.  290:19433-19444. 2015
    2015 Trib3 is elevated in Parkinson’s disease and mediates death in Parkinson’s disease models 2015
    2014 Formation of α-synuclein lewy neurite-like aggregates in axons impedes the transport of distinct endosomes 2014
    2014 Unique functional and structural properties of the LRRK2 protein ATP-binding pocket.  Journal of Biological Chemistry.  289:32937-32951. 2014
    2014 Differential LRRK2 expression in the cortex, striatum, and substantia nigra in transgenic and nontransgenic rodents.  Journal of Comparative Neurology.  522:2465-2480. 2014
    2014 Abrogation of α-synuclein -mediated dopaminergic neurodegeneration in LRRK2-deficient rats 2014
    2014 Addition of exogenous α-synuclein preformed fibrils to primary neuronal cultures to seed recruitment of endogenous α-synuclein to Lewy body and Lewy neurite-like aggregates.  Nature Protocols.  9:2135-2146. 2014
    2013 Reduction of synaptojanin 1 accelerates aβ clearance and attenuates cognitive deterioration in an alzheimer mouse model.  Journal of Biological Chemistry.  288:32050-32063. 2013
    2013 Calcium entry and α-synuclein inclusions elevate dendritic mitochondrial oxidant stress in dopaminergic neurons 2013
    2013 Lewy body-like α-synuclein aggregates resist degradation and impair macroautophagy.  Journal of Biological Chemistry.  288:15194-15210. 2013
    2012 Role of dynamin, synaptojanin, and endophilin in podocyte foot processes.  Journal of Clinical Investigation.  122:4401-4411. 2012
    2012 TMEM106B, the risk gene for frontotemporal dementia, is regulated by the microRNA-132/212 cluster and affects progranulin pathways 2012
    2012 Pharmacological rescue of mitochondrial deficits in iPSC-derived neural cells from patients with familial Parkinson's disease.  Science Translational Medicine.  4. 2012
    2011 Exogenous α-Synuclein Fibrils Induce Lewy Body Pathology Leading to Synaptic Dysfunction and Neuron Death.  Neuron.  72:57-71. 2011
    2011 Constitutive activated Cdc42-associated kinase (Ack) phosphorylation at arrested endocytic clathrin-coated pits of cells that lack dynamin 2011
    2010 Phosphatidylinositol-4-phosphate 5-kinases and phosphatidylinositol 4,5-bisphosphate synthesis in the brain.  Journal of Biological Chemistry.  285:28708-28714. 2010
    2009 The β- and γ-isoforms of type I PIP5K regulate distinct stages of Ca2+ signaling in mast cells.  Journal of Cell Science.  122:2567-2574. 2009
    2008 Wnt3a-mediated formation of phosphatidylinositol 4,5-bisphosphate regulates LRP6 Phosphorylation.  Science.  321:1350-1353. 2008
    2007 Phosphoinositides' link to neurodegeneration.  Nature Medicine.  13:784-786. 2007
    2005 Arf family GTPases: roles in membrane traffic and microtubule dynamics.  Biochemical Society Transactions.  33:1269-1272. 2005
    2005 Isoform-selective effects of the depletion of ADP-ribosylation factors 1-5 on membrane traffic 2005
    2004 Immunohistochemical localization of proteins in the nervous system..  Current protocols in neuroscience / editorial board, Jacqueline N. Crawley ... [et al.].  Chapter 1. 2004
    2004 Muscarinic acetylcholine receptor subtypes in cerebral cortex and hippocampus.  Progress in Brain Research.  145:59-66. 2004
    2003 Altered Striatal Function and Muscarinic Cholinergic Receptors in Acetylcholinesterase Knockout Mice.  Molecular Pharmacology.  64:1309-1316. 2003
    2003 Altered hippocampal muscarinic receptors in acetylcholinesterase-deficient mice.  Annals of Neurology.  53:788-796. 2003
    2003 Agonist-induced endocytosis of lysophosphatidic acid-coupled LPA1/EDG-2 receptors via a dynamin2- and Rab5-dependent pathway.  Journal of Cell Science.  116:1969-1980. 2003
    2003 Regulation of muscarinic acetylcholine receptor function in acetylcholinesterase knockout mice 2003
    2002 Rab11a and myosin Vb regulate recycling of the M4 muscarinic acetylcholine receptor 2002
    2002 Characterization of central inhibitory muscarinic autoreceptors by the use of muscarinic acetylcholine receptor knock-out mice 2002
    2001 Rab5-dependent Trafficking of the m4 Muscarinic Acetylcholine Receptor to the Plasma Membrane, Early Endosomes, and Multivesicular Bodies.  Journal of Biological Chemistry.  276:47590-47598. 2001
    1999 Sensitization to daily morphine injections in rats with unilateral lesions of the Substantia nigra 1999
    1997 Naltrexone and alcohol dependence: Role of subject compliance.  Archives of General Psychiatry.  54:737-742. 1997
    1996 Naltrexone in the treatment of alcoholism: A clinical review.  Alcohol.  13:35-39. 1996
    1995 Medical management of alcohol dependence: Clinical use and limitations of naltrexone treatment.  Alcohol and Alcoholism.  30:789-798. 1995
    Inhibition of LRRK2 kinase activity promotes anterograde axonal transport and presynaptic targeting of α-synuclein

    Chapter

    Year Title Altmetric
    2018 Prion-like propagation of pathology in Parkinson disease.  321-335. 2018
    2013 Synuclein-Mitochondrial Interactions in Substantia Nigra Dopamine Neurons.  126-127. 2013

    Research Overview

  • Dr. Volpicelli-Daley discovered that exposure of neurons to seeds of amyloid fibrils composed of alpha-synuclein causes endogenous alpha-synuclein to form aggregates that morphologically and biochemically resemble those found in Parkinson's disease. The goal of the lab is to stop this pathogenic templating of alpha-synuclein to halt the progression of Parkinson’s disease. The lab also seeks to understand the neurobiologic mechanisms by which alpha-synuclein aggregates cause neuron dysfunction.

    We have several projects in the lab. We are determining how LRRK2, the most common genetic cause of Parkinson's disease, impacts trafficking of alpha-synuclein to the presynaptic terminals. We are also determining how genes implicated in PD increase cognitive dysfunction. The lab utilizes biochemical techniques to identify novel proteins and protein interactions involved in alpha-synuclein aggregate formation. The lab performs super-resolution microscopy to image protein localization at nanoscale resoluction. We perfom live cell imaging in neurons to measure calcium transients and axonal transport. We use rodent models to determine the impact of PD genes on behavior.

    Finally, Dr. Volpicelli-Daley is dedicated to the success of graduate and undergraduate students in the lab that have received prestigious fellowhships awards, and have successful publishing records.

    • Principal Investigator On

  • Alpha-Synuclein Aggregate Induced Synapse Loss is a Pathological Event contributing to Lewy Body Dementias  awarded by National Institute of Neurological Disorders and Stroke/NIH/DHHS
  • Antisense Oligonucleotide Knockdown of the Transcriptional Repressor RIP140 to Enhance Survival of Dopaminergic Neurons in a Mouse of PD  awarded by SOUTHERN RESEARCH INSTITUTE
  • Defining Alpha-Synuclein Conformers Responsible for PD Phenotypes in Mice  awarded by Fox (Michael J.) Foundation for Parkinson's Research
  • Expansion Microscopy to Visualize Intracellular aSyn Pathology  awarded by Fox (Michael J.) Foundation for Parkinson's Research
  • Further Validation of SIRT3 as a Disease Modifying Agent in Parkinson's Disease  awarded by University of Toronto
  • Innate and Adaptive Immunity in Parkinson Disease - Core C: Animal Core  awarded by National Institute of Neurological Disorders and Stroke/NIH/DHHS
  • Investigating the Role of Lipid Metabolism in Protein Aggregation and Neurodegenerative Disease Progression  awarded by SEATTLE INSTITUTE FOR BIOMEDICAL AND CLINICAL RESEARCH
  • LRRK2 Regulation of Glucocerebrosidase Activity: Role of Rab10 And Pathological Characterization  awarded by American Parkinson Disease Association
  • LRRK2 in Pathological Synuclein Transmission  awarded by American Parkinson Disease Association
  • LRRK2 in Pathological Synuclein Transmission  awarded by American Parkinson Disease Association
  • Private Grant  awarded by MERCK SHARP & DOHME CORP
  • Private Grant  awarded by OCCAMZRAZOR
  • Reducing Tau as a Therapeutic Strategy for Improving Cognitive Dysfunction in Parkinson's Disease  awarded by DOD - ARMY MEDICAL RESEARCH ACQUISITION ACTIVITY
  • Rescue of Parkinson’s Disease Related Neuronal Defects by LRRK2 and Rab GTPase Substrates  awarded by Parkinson's Foundation
  • Role of Presynaptic Targeting of Alpha-Synuclein in the Pathogenesis of Parkinson's Disease and Dementia with Lewy Bodies  awarded by National Institute of Neurological Disorders and Stroke/NIH/DHHS
  • Seeking Neuro-Protection Via a Novel Complex-1 Chaperone Supplement  awarded by Fox (Michael J.) Foundation for Parkinson's Research
  • Understanding and Manipulating Cellular and Circuit-level Vulnerability to Neurodegeneration in Parkinson’s Disease  awarded by Yale University
  • Validate PFF a-syn-induced Inflammatory Phenotype in Mice  awarded by Fox (Michael J.) Foundation for Parkinson's Research

    • Investigator On

  • Alpha-Galactosidase A: A Novel Target for Reducing Alpha-Synuclein Toxicity  awarded by National Institute of Neurological Disorders and Stroke/NIH/DHHS
  • Co-Pathologies Drive Neuroinflammation and Progression in PD  awarded by RUSH UNIVERSITY
  • Co-Pathologies Drive Neuroinflammation and Progression in PD  awarded by Arizona State University
  • Contribution of the Interaction Between Synuclein and Tau in the Pathophysiology of Dementia with Lewy Bodies  awarded by National Institute on Aging/NIH/DHHS
  • Efficacies and Pharmacodynamic Assays for LRRK2 Small-Molecule Inhibitors  awarded by National Institute of Neurological Disorders and Stroke/NIH/DHHS
  • Efficacies and Pharmacodynamic Assays for LRRK2 Small-Molecule Inhibitors  awarded by National Institute of Neurological Disorders and Stroke/NIH/DHHS
  • Identification of Robust and Relevant Pre-Clinical Phenotypes for LRRK2 Therapeutics  awarded by Fox (Michael J.) Foundation for Parkinson's Research
  • Innate and Adaptive Immunity in Parkinson Disease  awarded by National Institute of Neurological Disorders and Stroke/NIH/DHHS
  • Innate and Adaptive Immunity in Parkinson Disease  awarded by National Institute of Neurological Disorders and Stroke/NIH/DHHS
  • 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
  • Lysosomal Enhancement Strategies in Dopaminergic Neurodegeneration  awarded by National Institute of Neurological Disorders and Stroke/NIH/DHHS
  • Mechanisms of LRRK2 Mediated Neurotoxicity  awarded by National Institute of Neurological Disorders and Stroke/NIH/DHHS
  • Role of Rab27b in Synucleinopathies  awarded by National Institute of Neurological Disorders and Stroke/NIH/DHHS
  • Role of Rab27b in Synucleinopathies  awarded by National Institute of Neurological Disorders and Stroke/NIH/DHHS
  • The Edmond J. Safra Fellowship in Movement Disorders 2019 Program  awarded by Fox (Michael J.) Foundation for Parkinson's Research
  • The Nigral Molecular Clock and Vulnerability to Neurodegeneration  awarded by National Institute of Neurological Disorders and Stroke/NIH/DHHS
  • Validation of CCR2-Dependent Monocyte Entry in Alpha-Synuclein-Induced Toxicity  awarded by Fox (Michael J.) Foundation for Parkinson's Research

    • Education And Training

  • Emory University Biochemistry, Postdoctoral Fellowship
  • Yale University Cell Biology, Postdoctoral Fellowship
  • Doctor of Philosophy in Neuroscience, Emory University 2003
  • Bachelor of Science or Mathematics, Franklin & Marshall College 1993

    • Full Name

  • Laura Volpicelli-Daley