Members

Matthew J LaVoie

Matthew J LaVoie PhD

Director, Center Of Translational Research In Neurodegenerative Disease
Department: MD-NEUROLOGY-MOVEMENT DISORDER
Phone: (352) 273-5579
Mailing Address:
PO Box 100159
GAINESVILLE FL 32610
Physical Address:
1275 CENTER DR
GAINESVILLE FL 32610
Research Summary:

The overall goal of the LaVoie lab is to elucidate the earliest molecular events responsible for adult onset neurodegenerative diseases. We approach these devastating disorders from both the perspective that specific inherited gene mutations linked to familial forms can provide valuable insight, as well as maintaining a focus on aspects of the far more common sporadic forms. The LaVoie lab employs a diverse array of state-of-the-art tools to accomplish these goals including a series of novel knockin animal models, iPSC-based neuronal and glial cultures, and CRISPR/Cas9 genome editing.

Our focus on familial Parkinson’s disease is centered on pathogenic mutations in the Parkin and LRRK2 genes. Parkin is an ubiquitin E3 ligase which is highly expressed in neurons. Autosomal recessive, loss-of-function mutations in the Parkin gene are associated with an often early onset form of Parkinson’s disease. The precise role of parkin within the neuron is not clear, however, data from multiple model organisms strongly support both homeostatic and pro-survival functions of parkin that impact mitochondrial biology. Our ongoing work seeks to understand how a primarily cytosolic protein such as parkin possesses such a potent influence on mitochondria.

LRRK2 is a large multi-domain kinase linked to PD via autosomal dominant inheritance of several mutations that span the entire protein. Given the complex nature of the LRRK2 protein itself, and the fact that PD-linked mutations occur in multiple domains, a primary goal of our work is to understand the physiological function and regulation of wild-type LRRK2. Then, we hope to uncover divergent behaviors and consequences of various PD-linked mutants (e.g. R1441C/G/H, Y1699C, G2019S, I2020T). Our recent work has shown that the highly active LRRK2 dimer resides at the cell membrane, regulates lysosomal function and influences the neuronal metabolism of alpha-synuclein, a protein whose aggregation is believed to drive the pathogenesis in PD. Ongoing work seeks to determine the physiological and pathological implications of this LRRK2 mutation, its role in idiopathic disease, and crosstalk between LRRK2 signaling pathways and other genetic risk factors for PD.

In seeking to understand the pathological consequences of the widely reported mitochondrial Complex-1 dysfunction in sporadic PD, the LaVoie lab utilizes a combination of novel cell culture and animal models deficient in various genes critical to mitochondrial function to examine the primary pathological events that follow mitochondrial disturbance. In addition, we are uncovering novel mechanisms to improve mitochondrial function in the hopes to identify opportunities slow or halt disease progression in patients.

Research Interests:
  • Alzheimer’s Disease
  • Lewy Body Dementia
  • Parkinson’s disease
  • Progressive Supranuclear Palsy (PSP)
Publications:
Grants:
  • Jul 2023 ACTIVE
    Iron homeostasis and inflammatory responses in human LRRK2 astrocytes
    FOX FOU, MICHAEL J · Co-Project Director/Principal Investigator
  • Dec 2022 ACTIVE
    Dysregulation of iron homeostasis by mutant LRRK2 in human neurons
    NATL INST OF HLTH NIA · Co-Investigator
  • Sep 2022 ACTIVE
    Deciphering tau phosphorylation and Abeta/tau strain interactions in Alzheimers pathogenesis
    NATL INST OF HLTH NIA · Co-Investigator
  • Jun 2022 ACTIVE
    Protection of dopaminergic neuronal function
    PARKINSONS FOU · Other
  • Mar 2021 – Sep 2023
    Role of LRRK2 in Gcase-mediated alterations in lysosome function and alpha-synuclein metabolism
    FOX FOU, MICHAEL J · Principal Investigator
  • Jul 2020 ACTIVE
    PATHOLOGIC LRRK2 SIGNALING IN FAMILIAL AND IDIOPATHIC PARKINSON'S DISEASE
    NATL INST OF HLTH NINDS · Principal Investigator
  • May 2020 – May 2022
    Role of Parkin in Familial and Idiopathic Parkinson's Disease
    NATL INST OF HLTH NINDS · Principal Investigator
Education:
  • 2000
    PhD in Neuroscience
    University of Pittsburgh
  • 1995
    BA/BS in Biology/Psychology
    Rutgers College
Richard D Batchelor
Department: MD-NEUROLOGY-MOVEMENT DISORDER

Richard D Batchelor

Laboratory Technician
Phone: (352) 294-5308
Aravindraja Chairmandurai
Department: MD-NEUROLOGY-MOVEMENT DISORDER

Aravindraja Chairmandurai PhD

Assistant Scientist
Phone: (352) 273-5550
Elizabeth A Chapman
Department: MD-NEUROLOGY-MOVEMENT DISORDER

Elizabeth A Chapman

GRADUATE AST-R
Phone: (352) 273-8601
Dwindy Gerbier
Department: MD-NEUROLOGY-MOVEMENT DISORDER

Dwindy Gerbier

Laboratory Technician
Phone: (352) 273-5550
Thomas B Ladd
Department: MD-NEUROLOGY-MOVEMENT DISORDER

Thomas B Ladd

Scientific Research Manager
Phone: (352) 273-9690
Adamantios Mamais
Department: MD-NEUROLOGY-MOVEMENT DISORDER

Adamantios Mamais MSc, PhD

Hough Family Fellow, Research Assistant Professor Of Neurology
Phone: (352) 273-5550
Nitya Subrahmanian
Department: MD-NEUROLOGY-MOVEMENT DISORDER

Nitya Subrahmanian

Research Assistant Professor
Phone: (352) 273-5550