Laura Volpicelli-Daley

Laura Volpicelli-Daley
Associate Professor

Associate Professor (P), Neurology , School of Medicine
Associate Scientist (C), Comprehensive Neuroscience Center , General Clinical Research Center
Associate Scientist (C), Neurodegeneration and Experimental Therapeutics (CNET) , Neurology
Scientist (C), Alzheimer's Disease Center , Neurology
Associate Scientist (C), Civitan International Research Center , Academic Joint Departments
Assistant Professor (S), Neurobiology , Academic Joint Departments

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	Inhibition of LRRK2 kinase activity promotes anterograde axonal transport and presynaptic targeting of α-synuclein. Acta Neuropathologica Communications. 9. 2021
2021	Molecular Mechanisms Underlying Synaptic and Axon Degeneration in Parkinson’s Disease. Frontiers in Cellular Neuroscience. 15. 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. 21:8043-8043. 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
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	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. Archives of General Psychiatry. 54:737-737. 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. 1995
	Inhibition of LRRK2 kinase activity promotes anterograde axonal transport and presynaptic targeting of α-synuclein

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.