Research Team – GBA1 Canada

PI

Ziv Gan-Or

MD, PhD

Ziv Gan-Or

MD, PhD

Associate Professor, The Neuro (Montreal Neurological Institute-Hospital), Department of Neurology and Neurosurgery, Department of Human Genetics, McGill University

Dr. Gan-Or is a leading geneticist in the field of Parkinson’s disease and spearheads the world’s largest effort on RBD genomics. He is an expert on GBA1, with >50 publications on GBA1 and its genetics, function, and clinical aspects. He has been working with pharmaceutical companies on GBA1 and its modifiers as therapeutic targets for PD. He also serves on several scientific advisory boards to help facilitate precision medicine in PD treatment. At the Neuro, he is the co-director of the Clinical Research Unit (CRU), the director of the Neurodegenerative Disorders Research Group, and leads the Neurogenomics and Precision Medicine lab.

CO-PI

Guy Rouleau

OC, OQ, MD, PhD, FRCP(C), FRSC

Guy Rouleau

OC, OQ, MD, PhD, FRCP(C), FRSC

Director, The Neuro (Montreal Neurological Institute and Hospital)

Dr. Rouleau, the director of The Neuro is a world-leading neurogeneticist, with decades of experience in research and in leadership of large-scale projects. He will use this experience to mentor and assist Dr. Gan-Or with the management of the project, and his involvement demonstrates the commitment of The Neuro for the success of the project. He has been collaborating with Dr. Gan-Or on GBA1, different genetic modifiers of GBA1 and RBD in the past 9 years.

Edward Fon

MD, MSc

Edward Fon

MD, MSc

Professor, Department of Neurology and Neurosurgery, McGill University Scientific director of The Neuro and the leader of the Quebec Parkinson Network

Dr. Fon, is a movement Disorders specialist and a leading expert in the molecular biology of Parkinson’s disease. His research is focused on understanding the mechanisms underlying Parkinson’s disease, RBD and similar disorders, with specific expertise on generating patient-derived cell models and developing and performing different assays. Together with Dr. Gan-Or and Durcan he has several research projects funded by MJFF to study GBA1 and modifier genes.

COLLABORATORS

Jeremy Van Raamsdonk

PhD

Jeremy Van Raamsdonk

PhD

Associate Professor, McGill University and Research Institute of the McGill University Health Centre

Dr. Van Raamsdonk is a molecular geneticist studying the biology of aging, biological resilience and neurodegenerative disease primarily using C. elegans models. With extensive experience with animal models of Parkinson’s disease, he will generate and characterize C. elegans genetic models relevant for GBA1 that will be used for basic and translational research.

Martin Parent

PhD

Martin Parent

PhD

Full professor, Université Laval

Dr. Martin Parent uses different animal models, including non-human primates and mice, to characterize neural circuits in the basal ganglia, with specific interest in models of Parkinson’s disease. He is in charge of large postmortem human brain bank from individuals who had PD and will use these resources for GBA1-specific research within this project.

Ronald Postuma

MD, MSc

Ronald Postuma

MD, MSc

Professor, Department of Neurology and Neurosurgery, McGill University. Director of the Division of Neurology, MUHC

Dr. Postuma is one of the world leading clinicians and clinical researchers in RBD. He has published seminal papers on clinical aspects of RBD including diagnosis, natural history and care. He has several projects on GBA1 in RBD, which also include genetics and lipidomics in RBD patients with and without GBA1 mutations.

Jean-François Trempe

PhD

Jean-François Trempe

PhD

Associate Professor, Department of Pharmacology & Therapeutics, McGill University

Dr. Trempe is a structural biologist and the director of the Proteomics Platform at the Research Institute of the McGill University Health Centre (RI-MUHC). He will lead the structural studies of GBA1 and different genetic modifiers in this project.

Thomas Durcan

PhD

Thomas Durcan

PhD

Assistant Professor in the Department of Neurology and Neurosurgery, McGill University. Director of the early drug discovery unit at The Neuro.

Dr. Durcan and his team specialize in generating patient-derived models, including brain organoids, and performing screens of compound libraries using different assays. He is involved in several projects on GBA1 and modifier genes.

Gary Armstrong

PhD

Gary Armstrong

PhD

Associate Professor in the Department of Neurology and Neurosurgery, McGill University

Dr. Armstrong is a molecular biologist studying neurodegenerative disorders, mainly ALS, using zebrafish. His team has been developing a zebrafish drug screening platform and will generate zebrafish with specific genetic mutations in the fish ortholog of GBA1

Madeleine Sharp

Assistant Professor in the Department of Neurology and Neurosurgery, McGill University

Dr. Sharp is a Movement Disorders specialist, with a research program focused on cognitive decline in individuals with neurodegenerative disorders. In this project she will lead research on cognitive decline in GBA1 variant carriers and in RBD.

Massimo Pandolfo

Professor (Clinical), Department of Neurology and Neurosurgery, McGill University, Co-director, The Neuro (Montreal Neurological Institute-Hospital)

Dr. Pandolfo is neurologist and a researcher with an extensive background in neurogenetics, cell and animal models and translational research. He will coordinate the collaboration with The Neuro’s clinical research unit.

Nicolas Dupré

MD MSc FRCP FAAN

Nicolas Dupré

MD MSc FRCP FAAN

Director of the Neuromuscular and Neurogenetic Diseases Clinic of the CHU de Québec – Université Laval

Dr. Dupré is a neurologist expert in movement disorders. He is the co-director of the Quebec Parkinson Network, also responsible for the Quebec City site of the Canadian-Open Parkinson Network and he is heavily involved in multiple research projects in Parkinson’s disease, including on GBA1. He took part in the discovery of a founder of French-Canadian GBA1 mutations that may lead to RBD and Parkinson’s disease.

Peter McPherson

PhD

Peter McPherson

PhD

Professor, Neurology and Neurosurgery and Anatomy and Cell Biology, McGill University

Dr. McPherson, a Distinguished James McGill Professor, is an expert in molecular cell biology. His lab uses biochemical, molecular, structural, genetic, and cellular approaches to study mechanisms underlying neurological disorders, including Parkinson’s disease. He is a founding member of YCharOS, an Open Science organization dedicated to characterization of commercial antibodies.

Austen J Milnerwood

PhD

Austen J Milnerwood

PhD

Associate Professor, Director Integrated Program in Neuroscience Rotation Program, Department of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University

Dr. Milnerwood is a physiologist and cell biologist at The Neuro, with major expertise in synapse development, function, and degeneration. He is expert in genetic mouse and human cell models, extensively studying Parkinson’s disease endolysosome proteins VPS35 & LRRK2; both of which are thought to regulate GBA1 function

TRAINEES

Emma Somerville

BSc

Emma Somerville

BSc

PhD Candidate, NAP-Med lab, McGill University. G-Can genetics data analyst.

Emma studies the genetic basis of Parkinson’s disease and REM-sleep behaviour disorder, and how genetics interacts with biomarkers to help inform clinical trials for drug development and precision medicine. Emma is well-versed in computational and bioinformatic methods, which she puts to use for G-Can by leading the data analysis for the genetic validation of GBA1 variants. Sequencing of GBA1 can be unreliable due to the close proximity of its pseudogene, so thorough analysis using various data types is required to confirm the existence of mutations. These validated variants can then be used in future research efforts and to aid in participant selection for GBA1-based clinical trials.

Andrew Bayne

MSc

Andrew Bayne

MSc

PhD candidate, Department of Pharmacology & Therapeutics, McGill University, Montréal, Québec, Canada; Centre de Recherche en Biologie Structurale, Montréal, Québec, Canada

Andrew is a PhD candidate in the lab of Jean-François Trempe at McGill University, which focuses on the structure and function of proteins implicated in Parkinson’s disease (PD) and mitochondrial quality control. In his work, Andrew utilizes a variety of bioinformatics, structural, and biochemical approaches to understand how mitochondrial dysfunction underlies PD pathophysiology. As a member of the GBA1 Canada initiative, Andrew will focus on the structural and mutational analysis of GBA and will primarily work on developing the web server for the structural visualization and interrogation of GBA variants for their downstream characterization.

Clarisse Orniacki

PhD

Clarisse Orniacki

PhD

Postdoctoral researcher, Department of Neurology and Neurosurgery, McGill University

Variants of the GBA1 gene encoding the lysosomal enzyme glucocerebrosidase are one of the most common risk factors for Parkinson’s Disease (PD). In addition, mutations in other lysosomal proteins have recently been linked to increased risk and earlier age at onset in GBA1-associated PD, suggesting an important role for lysosomal proteins in developing the disease. My projects in the lab use cellular models including dopaminergic neurons and microglia derived from human iPSC to characterize the roles of these lysosomal protein in the context of PD, and to understand the molecular mechanisms behind greater susceptibility to disease conferred by patient’s mutations. Shedding light on these mechanisms is key to finding relevant targets and improving the treatments of PD.

Sitki Cem Parlar

BSc

Sitki Cem Parlar

BSc

MSc Student, NAP-MED Lab, McGill University

Sitki completed his B.Sc. with Neuroscience Major at McGill University. He is studying the role of specific domains in Parkinson’s disease-related in disease risk and development. Sitki holds a CIHR (Canadian Institutes of Health Research) grant to support his research endeavors.

Isabella Pietrantonio

BSc

Isabella Pietrantonio

BSc

MSc Student, Dr. Edward Fon’s Lab, McGill University

The accumulation of protein aggregates composed mainly of alpha-synuclein is a major hallmark of Parkinson’s Disease (PD). The mechanisms through which these aggregates exert their toxicity have not been fully elucidated, yet their ability to disrupt degradation systems within the cell has been suggested. The lysosome is at the heart of these degradation pathways, therefore highlighting its importance. More recently, the activation of the stimulator of interferon genes (STING) pathway has been associated to several neurological diseases, including PD, with a particular focus on lysosomal homeostasis. Therefore, my project aims to explore the role of lysosomal function in PD pathology by investigating whether GWAS associated lysosomal PD genes lead to STING activation or impaired STING degradation.

Amirhossein Rajabi Vajargah

Bsc

Amirhossein Rajabi Vajargah

Bsc

MSc Student, NAP-MED Lab, McGill University

Amir is harnessing multiomics data alongside advanced statistical and computational methods to study the role of the lysosomal glycosphingolipid pathway in synucleinopathies

Lydia Chougar

MD, PhD

Lydia Chougar

MD, PhD

Post-Doctoral Researcher, Dr Alain Dagher's Lab

Lydia Chougar is a medical doctor and postdoctoral researcher in Dr Alain Dagher’s lab at the Neuro – Montreal Neurological Institute, McGill, since November 2023. Her research aims to understand the physiopathological mechanisms underlying Parkinson’s disease and related disorders and develop biomarkers useful for the early diagnosis and disease progression monitoring using high and ultra-high field strength MRI. She is particularly interested in bridging research and clinical practice by translating research-developed diagnostic methods into clinical settings.

PI, co-PIs and Collaborators

PI

Ziv Gan-Or

CO-PI

Guy Rouleau

Edward Fon

COLLABORATORS

Jeremy Van Raamsdonk

Martin Parent

Ronald Postuma

Jean-François Trempe

Thomas Durcan

Gary Armstrong

Madeleine Sharp

Massimo Pandolfo

Nicolas Dupré

Peter McPherson

Austen J Milnerwood

TRAINEES

Emma Somerville

Andrew Bayne

Clarisse Orniacki

Sitki Cem Parlar

Isabella Pietrantonio

Amirhossein Rajabi Vajargah

Lydia Chougar

FUNDING PARTNERS