Professor Catherine Larochelle and Professor Nathalie Arbour

Professor Catherine Larochelle and Professor Nathalie Arbour

 

Catherine Larochelle MD, PhD, FRCPC
Clinical assistant professor
Department of Neurosciences,
Université de Montréal
Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM)
Canada

Catherine Larochelle obtained an MD degree in 2004 and an MSc degree in 2005 from the Université Laval, Québec, Canada. She completed her neurology residency training at the Université de Montréal in 2009, before completing a PhD degree in 2014 in the laboratory of Dr Alexandre Prat, working on adhesion molecules implicated in recruitment of pathogenic T cells in central neuroinflammation. She then conducted a post-doctoral fellowship at the Universitätmedizin Mainz, Germany, under the supervision of Dr Frauke Zipp, focusing on interactions between immune cells and central neuroglial cells in vitro and in vivo. Since 2013 Professor Larochelle has been a staff neurologist at the Centre Hospitalier de l’Université de Montréal (CHUM), and in 2016 became an assistant clinical professor and researcher at the CHUM research center.

Professor Larochelle’s research program focuses on the contribution of the peripheral immune system to neuroglial dysfunction in neuroinflammatory disorders. Building on complementary clinical and scientific skills, her team performs ex vivo and in vitro assays on human primary cells, in situ studies on human brain sections from MS and control subjects, as well as in vivo experiments including intravital microscopy on animal models. Her research program is funded by the Banting Foundation and the Savoy Foundation.

Nathalie Arbour PhD
Associate professor
Department of Neurosciences,
Université de Montréal
Neuroscience Axe Leader
Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM)
Canada

Nathalie Arbour obtained a PhD in virology and immunology at INRS-Armand-Frappier in Québec, Canada. She completed post-doctoral training at the Scripps Research Institute under the supervision of Dr Michael BA Oldstone and subsequently at the Montréal Neurological Institute in the team of Dr Jack Antel. Since 2006, she has been a professor at the Université de Montréal and researcher at the Centre de Recherche du CHUM (the Université de Montréal affiliated hospital).

Her research program aims to characterize and understand the interactions between the immune system and the central nervous system (CNS), especially the roles of T cells in the context of multiple sclerosis (MS). Her research strategy is to first identify molecules or mechanisms that are specifically altered in human samples obtained from patients with MS. Her team then investigates the mechanistic impact of such factors using primary cultures of human immune and CNS cells. Finally, using relevant animal models of MS, Nathalie Arbour and her team confirm and dissect the role played by these identified mechanisms and test in vivo strategies to correct these altered factors and thus validate them as bona fide therapeutic targets. The Arbour’s team performs mechanistic studies on human cells as well as on relevant animal models using a wide array of complementary techniques including multiparametric flow cytometry, Western blot, qRT-PCR, co-culture systems, and immunohistochemistry.

Nathalie Arbour has published more than 56 papers building on data obtained from both human and mouse systems. Her research program is funded by the Multiple Sclerosis Society of Canada, the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada.

Immunosenescence as a predictor of MS progression

Biological aging is associated with alterations of the immune profile called immunosenescence. Repeated antigen encounter accelerates this process and as such recent studies have hinted that accelerated immunosenescence occurs in multiple sclerosis (MS). Age is the strongest predictive factor for onset of progression in MS; we therefore hypothesize that (biological) age-related modifications of the peripheral immune system represent relevant biomarkers for MS progression, and can predict resistance to treatment.

Our goal is to analyze the expression of immunosenescence, age-sensitive immune markers and mediators in the peripheral blood (PB) of MS patients, and to correlate those markers with age, clinical phenotype, progression and treatment response in both cross-sectional and prospective studies.

Our preliminary data shows that the CD4:CD8 ratio as well as tumor necrosis factor (TNF), interleukin-18 (IL-18) and brain-derived neurotrophic factor (BDNF) levels correlate with age, and that age-related variations are more pronounced in MS than in healthy controls. We now propose to use a large cohort of 200 untreated MS patients with MS, 200 treated patients with MS and 150 healthy controls to i) characterize age-sensitive immune markers in PB of patients with MS versus controls in relation with age, ii) determine the value of age-sensitive immune markers as biomarkers for progression in MS and iii) establish the impact of disease-modifying therapies on age-sensitive immune markers in MS in relation to age and to treatment outcome.

With this study we expect to identify peripheral blood age-sensitive immune markers that are correlated to disease progression and treatment response, and could represent biomarkers for progression in MS.

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