Multiple Sclerosis Society of Canada

Mechanisms of Disease

The initiation, progression, and dissemination of MS are important areas of focus for studies in this category. Researchers are exploring the structural and functional changes that occur in MS, including inflammation, neurodegeneration, and myelin repair.

Mechanisms of Progression

Researchers

Project Title


Researcher
Affiliation
Funding Term
Funding
Immune cell influences on neuronal viability and repair Dr. Alyson Fournier Montreal Neurological Institute 2016-2019 $370 512.06
Immune cell-microbiome interactions and neuroinflammation Dr. Jennifer Gommerman University of Toronto 2016-2019 $365 500
The Role of Antibody-Secreting Cells in MS/EAE Dr. Jennifer Gommerman University of Toronto 2018-2021 $370 500
Characterizing the neuroprotective roles of bHLH proteins Npas4 and ARNT2 in inflammatory neurodegeneration related to multiple sclerosis Dr. Jacqueline Quandt University of British Columbia 2018-2021 $346 400
Role of neutrophils as antigen-presenting cells in autoimmune demyelination Dr. Luc Vallières Laval university 2016-2019 $424 452
Elevated axonal and myelin injury with aging: Mechanisms, prevention and prospective therapeutics for progressive multiple sclerosis Dr. Wee Yong University of Calgary 2018-2021 $420 140

Trainees

Project Title
Trainee
Affiliation
Award
Project Description

Epigenomic Analysis of Regulatory T cells in Multiple

Sclerosis

Matthew Lincoln

Yale University

Postdoctoral Fellowship MD

T cells are an important class of white blood cell that

normally fight infection but are dysfunctional in MS. The

project aims to identify the specific genes and mechanisms

that cause T cell dysfunction, so that these may be

corrected.

Astrocytic Factors That Impair Remyelination in the Ageing

Central Nervous System

Khalil Rawji

the University of Cambridge, Department of Clinical

Neurosciences

Postdoctoral Fellowship

The body's ability to repair the insulation around nerve

projections after injury slows with ageing. This project is

seeking to understand why repair slows down with ageing and

to potentially discover new treatments that can speed up

repair.

NLRX1 acts as an endogenous inhibitor of multiple sclerosis

Marjan Gharagozloo

Université de Sherbrooke

Studentship PhD

The goal of the research is to investigate how molecules

known as NOD-like receptors (NLRs) suppress initiation and

progression of MS.

Role of CD8+ T cells in progressive EAE.

Prenitha Mercy Ignatius Arokia Doss

Université Laval

Studentship PhD

Progressive multiple sclerosis (MS) is a phase of MS in

which there is neurological deficit without recovery and

immune cells play an important role in it. This project is

generating a mouse model that can recapitulate

progressive-MS seen in humans.

Uncovering and reversing causes of remyelination failure in

progressive multiple sclerosis - miR-145-5p regulates MYRF

in oligodendrocytes

Samantha Kornfeld

Ottawa Hospital Research Institute

Studentship PhD

The study aims to discover and understand molecules in the

progressive MS lesions that block repair processes. By

understanding the effects these molecules have, new methods

to overcome them to allow remyelination to occur can be

developed.

Elucidating Cortical Lesion Evolution in Multiple Sclerosis

Josefina Maranzano

McGill University

Studentship PhD

This project will identify and characterize the evolution

of MS lesions that affect the a brain region using two

different MRI scanners: one less powerful and available in

clinical practice, the other, more powerful, only available

for researchers.

Aging exaggerates lesion size and axonal injury following

demyelination: mechanisms and neuroprotection

Nathan Michaels

University of Calgary

Studentship PhD

Age is a critical risk factor for progressive Multiple

Sclerosis (MS). The project investigates the underlying

biology of age and lesion formation in the brain and spinal

cord to better understand the mechanisms of progressive MS.

Identifying pathogenic B cells in an animal model of

central nervous system autoimmunity and determining their

susceptibility to therapeutic depletion

Yodit Tesfagiorgis

University of Western Ontario

Studentship PhD

The goal of this project is to understand what an immune

cell, called the B cell, is doing both throughout the body

and specifically in the brain and spinal cord to contribute

to multiple sclerosis incidence and severity.

Elucidating the role of PPARd expression in microglial

cells during EAE

Ellinore Doroshenko

University Health Network - Toronto General Hospital

Research Institute

Studentship Msc

The project focuses on microglia, the immune cells that

home the brain and spinal cord, and looks at how they act

within a mouse model of MS-like disease.

Repair Processes

Researchers

Project Title
Researcher
Affiliation
Funding Term
Funding

Impact of IL-27 on MS pathobiology

Dr. Nathalie Arbour

Centre de Recherche du Centre Hospitalier de l’Université de Montréal

2017-2020

$383 138.25

Role and therapeutic potential of Neuregulin-1 as a modulator of neuroinflammation and remyelination in multiple sclerosis

Dr. Soheila Karimi

University of Manitoba

2017-2020

$358 321

Identifying New Molecular Mechanisms that Promote Myelin Maintenance and Remyelination

Dr. Timothy Kennedy

McGill University

2017-2020

$360 300

MicroRNA-145 is a key regulator of oligodendrocyte maturation and CNS myelination

Dr. Rashmi Kothary

Ottawa Hospital Research Institute

2017-2020

$301 920

Molecular mechanisms underlying T cell/oligodendrocyte interactions as target for neuroprotective strategies in MS

Dr. Catherine Larochelle

Université de Montréal

2018-2021

$367 000

Impact of MicroRNA-223 on Immune and Glial Cells in Multiple Sclerosis

Dr. Craig Moore

Memorial University

2016-2019

$344 104

Defining a dual role for VGF in the regulation of MS pathology

Dr. David Picketts

Ottawa Hospital Research Institute

2018-2021

$312 528

Investigating a novel inhibitory signaling mechanism that represses T cell-driven CNS autoimmunity

Dr. Manu Rangachari

Université Laval

2017-2020

$299 259

Characterizing the anti-inflammatory and disease-modifying potential of novel a7 nicotinic acetylcholine receptor silent agonist

Dr. Alain Simard

Université de Moncton

2017-2020

$355 821

Targeting Oligodendrocyte Maturation for the Study of Axonal Survival

Dr. Wolfram Tetzlaff

The University of British Columbia

2016-2019

$341 411

Novel Strategies to Enhance Intrinsic Repair following Demyelination

Dr. Valerie Verge

University of Saskatchewan

2015-2019

$297 783

Mechanisms and parameters of exercise-induced remyelination in mice

Dr. Wee Yong

University of Calgary

2016-2019

$412 636

Trainees

Project Title
Trainee
Affiliation
Award
Project Description


Innate and Adaptive Remyelination

Peggy Assinck

University of Edinburgh

Postdoctoral Fellowship

This research, albeit mechanistic in nature, will yield

important information about the repair process and help us

to identify the important pathways underlying the different

stages of repair and their importance in functional

recovery.

The therapeutic potential of the Th2 cytokine

interleukin-13 in multiple sclerosis

Chloé Hoornaert

Centre de Recherche du Centre Hospitalier de l’Université

de Montréal

Postdoctoral Fellowship

Having formerly established that the anti-inflammatory

factor interleukin-13 is neuroprotective in a mouse model

of MS (and other models of neuroinflammation), the goal of

the project is to investigate if this factor also holds

therapeutic promise in human MS.

The effect of the TH17-associated cytokine IL26 on CNS

barriers integrity: Implications for MS

Evelyn Peelen

Centre de Recherche du CHUM

Postdocotoral Fellowship

A protein, called IL26, is shown to fortify the barrier

between blood and brain to prevent harmful immune cells

from entering. Although this suggests a beneficial role in

MS, the project will further investigate the effect of IL26

on the defense system.

Establishing the role of DOCK8 in T and B cells in a murine

model of MS

Asanga Weliwitigoda

Benaroya Research Institute at Virginia Mason

Postdoctoral Fellowship

The project will is to understand how a protein, called

DOCK8, in immune cells can alter inflammation in the brain

and evaluate the potential of DOCK8 as as a therapeutic

target to treat MS.

Impact of IL-27 on T cells from Multiple Sclerosis patients

Marie-Laure Clénet

Centre de Recherche du CHUM

Studentship PhD

This study focuses on a molecule, called interleukin-27

(IL-27), whcih can diminish the severity of a mouse disease

mimicking MS. However, the impact of IL-27 in people living

with MS is still unknown.

Exploring the Clinical and Functional Significance of

Altered MiR-223 Expression in Multiple Sclerosis and its

Animal Models

Dylan Galloway

Memorial University of Newfoundland

Studentship PhD

The aims of the research project are to identify the role

that a small molecule plays in demyelination and brain

repair. This research will give insight into MS pathology,

and may have benefit as a MS biomarker or therapeutic agent

Investigating a Novel Mechanism that Promotes Myelin

Maintenance

Diane Nakamura

McGill University

Studentship PhD

Mitochondria are an essential component of the cell

responsible for energy and myelin production. The project

aims to determine how energy production by mitochondria is

regulated in the myelin-producing cells of the central

nervous system.

Identify the contribution of netrin-1 and netrin receptors

to remyelination following experimentally induced

demyelination

Samuel Clemot-DuPont

McGill University

Studentship Msc

Myelin is the protective insulating substance of nerve

fibers. Using a model of demyelination, loss of myelin

following injury, the project aim to examine the

contribution of proteins important for myelin maintenance,

to myelin stability and repair.

miRNA in EAE-related pain: a new perspective on

post-transcriptional regulation

Timothy Friedman

University of Alberta

Studentship Msc

Pain in MS is a major symptom for up to half of all MS

patients. The project investigates how the expression of

genes are controlled by small molecules called ‘microRNA’

and if a change in this control could result in the pain

seen MS.

Metabolic Control of Human Macrophage-Mediated Myelin

Phagocytosis: Implications for MS

Yun Hsuan (Elena) Lin

Montreal Neurological Institute, McGill University

Studentship Msc

The project examines immune cells termed ‘macrophages’

responsible for cleaning toxic cellular debris built up in

the brains of MS patients. The study focuses on

understanding how the internal processes of these cells

drive their beneficial function in disease.

Innate Immune Responses in Oligodendrocytes and Therapeutic

Strategies.

Leina Saito

University of Alberta

Studentship Msc

The project involves studying oligodendrocytes, which are

brain cells that makes myelin, a protective factor for

nerve fibres that is damaged in MS. The goal is to identify

if oligodendrocytes are able to generate an immune response

that may contribute to MS development.

Nerve Damage and Triggers of MS

Researchers

Project Title
Researcher
Affiliation
Funding Term
Funding

Inflammasome activation in the central nervous system: determinants and outcomes in progressive MS

Dr. Christopher Power

University of Alberta

2018-2021

$311 328

Targeting DICAM, a novel mediator of neuroinflammation, to treat MS

Dr. Alexandre Prat

Centre de Recherche du Centre Hospitalier de l’Université de Montréal

2018-2021

$360 000

Elucidating the role and regulation of astrocytes in multiple sclerosis

Dr. Shalina Ousman

University of Calgary

2017-2020

$314 776.62

Targeting novel functions of cysteine cathepsins to limit neuroinflammation

Dr. Robin Yates

University of Calgary

2016-2019

$346 506

Trainees

Project Title
Trainee
Affiliation
Award
Project Description


A novel mechanism of autoinflammatory induction by cysteine

protease Cathepsin Z in multiple sclerosis

Corey Arnold

University of Calgary

Postdoctoral Fellowship

In multiple sclerosis, certain cells no longer pass a

"safety inspection" by the immune system, and so the body

begins to attack itself. The project focuses on how cells

conduct this inspection, and reasons why it may go wrong.

The role of TMEM16A, a voltage-sensitive calcium-activated

chloride channel, on blood-brain barrier endothelial cells

during neuroinflammation.

Marc-André Lécuyer

University of Gottingen

Postdoctoral Fellowship

The goal of this project is to study the function TMEM16A,

a channel that allows ions to pass through the cell

membrane. Modulating TMEM16A might prevent the opening of

the blood-brain barrier and thus prevent disease

progression.

Immune cells influence on neurodegeneration and

neuroprotection through neuronal microRNAs regulation in

the optic nerve

Barbara Morquette

Montreal Neurological Institute, McGill University

Postdoctoral Fellowship

The deterioration of nerve fibers is a major component of

MS. The study will examine how immune cells trigger nerve

damage and the associated underlying molecular mechanisms.

This project will shed light on important therapeutic

targets for MS patients.

Advanced in vivo imaging of disease causing T and B cells

in a model of anti-myelin autoimmunty

Kate Parham

Western University

Postdoctoral Fellowship

In MS, components of the immune system interact/talk to

each other and then begin to attack myelin in the central

nervous system. This study will visualise these

interactions, revealing specific targetable characteristics

of a MS autoimmune response.

Investigating exosomal microRNAs as functionally relevant

disease biomarkers in MS

Stephanie Blandford

Memorial University of Newfoundland

Studentship PhD

The project looks to identify mechanisms of cellular

communication between the immune and nervous systems that

causes central nervous system damage and are also useful as

biomarkers to diagnose MS and differentiate between

different MS subtypes.

MCAM+ Cells Contribute to the Development of MS and Predict

its Progression

Marc Charabati

Centre de Recherche du CHUM

Studentship PhD

In MS, harmful immune cells infiltrate the brain and spinal

cord using specific cell surface molecules. The project

aims at exploring the contribution of MCAM, a molecule

present on the cell surface of blood vessels, to the

development of MS.

The role of integrin alpha8 in multiple sclerosis

Elizabeth Gowing

Centre de Recherche du CHUM

Studentship PhD

A group of proteins mediate the migration of inflammatory

immune cells across the blood-brain barrier in MS. The

study is identifying a new protein involved in this

process, that if blocked therapeutically, has the potential

to prevent MS disease activity.

The role of NKG2D in multiple sclerosis.

Ana Carmena Moratalla

Centre de Recherche du CHUM

Studentship PhD

Several studies showed that the immune system contributes

to the development of multiple sclerosis (MS). This study

investigates NKG2D, a molecule present on immune cells that

may be involved in the damage of nerve cells in the brain

of MS patients.

Development and characterization of animal models to study

MS-related trigeminal neuralgia

Kevin Thorburn

University of Alberta

Studentship PhD

The primary goal of the project is to understand how the

loss of myelin, and subsequent nerve damage, causes facial

pain in MS. To study this, facial sensitivity in mice that

have a disease very similar to MS is examined

Roles of miRNAs in neuron degeneration and repair

Yang Zhang

Montreal Neurological Institute, McGill University

Studentship Msc

The work aims to better understand the damage that brain

cells undergo when they are faced with inflammatory

challenges. Specifically, the project is looking at the

changes that occur within brain cells and what

interventions may prevent further damage from occuring.