Regular scientist at the CHU de Québec-Université Laval Research Center and full professor in the Department of Molecular Medicine at the Laval University Medical School. He is a renowned Canadian scientist who has contributed to the advancement and acceptance of major new scientific concepts. This work has demonstrated that the CNS is a highly immunologically active organ, with complex immune responses, mostly based on innate immune processes. Such responses implicate a continuum of heterogeneous cell types, both inside the CNS, in the periphery, and at their interface, the blood brain barrier (BBB). The goal here is to manipulate such a system to prevent and cure brain diseases. Canadian Research Chair in Neuroimmunology, Twice named Quebec laureate, Radio Canada and Le Soleil (2007 et 2013). Over 21 000 citations and H factor 81.
The immune system at the rescue of brain diseases
The inflammatory response in neurodegenerative diseases has often been linked to progressive neuronal damage. However, mounting evidence now suggests that CNS-resident microglia and circulating monocytes that differentiate into macrophages upon infiltrating the cerebral tissue may exert more beneficial effects on neurons than previously thought. The innate immune system in the brain exhibits a dual nature, as best exemplified by multiple sclerosis (MS) and Alzheimer’s disease (AD), which are often treated as being brain diseases with similar immune etiologies. In reality, they are rather “Yin and Yang” in that regard.
Thus, the role of the inflammatory response seems highly divergent between MS and AD. On the one hand, the marked and sustained activation of proinflammatory monocytic cells promotes demyelination and axonal loss in MS, but on the other hand, it is the anti-inflammatory (or inactivated) phenotype of these cells that allows CNS amyloid accumulation, neuronal dysfunction and memory decline in AD. This research program is focused on thoroughly unraveling the mechanistic details of the role of the innate immune system in the CNS, and how it can be tackled to exert neuroprotective actions.
Vision: A multidisciplinary approach, integrating innovative discoveries and technologies, to validate the concept of the neuroprotective properties of the innate immune system, to improve brain disease diagnosis and treatment.
Goals: Our main goals are to provide new biomarkers for diagnosis and to obtain proofs-of-concept that will lead to new treatments of brain diseases based on the neuroprotective functions of innate immunity.
Objectives: 1) To decipher the molecular and cellular mechanisms involved in the intimate control of different compartments of the brain innate immune system. 2) To identify new biomarkers from the analysis of subsets of circulating monocytes in preclinical models of MS and AD. 3) To use and develop complementary models and methods to understand how myeloid cells can be harnessed in exerting neuroprotective actions. 4) To validate new biomarkers and concepts of the beneficial role of the innate immune system in humans.
2705, boulevard Laurier
T4-50
Québec, Québec
Canada G1V 4G2
- Agharazii, MohsenAxis directorL'Hôtel-Dieu de Québec+1 418-525-4444, extension 15585+1 418-691-5562Mohsen.Agharazii@crchudequebec.ulaval.ca
6 rue McMahon
1896-2
Québec, QC
Canada G1R 3S1 - Ghareghani, MajidPostdoctoral fellowCHUL+1 418-525-4444, extension 42296majid.ghareghani@crchudequebec.ulaval.ca
2705, boulevard Laurier
T2-50
Québec, QC
Canada G1V 4G2 - Laflamme, NatalyEmployeeCHUL+1 418-525-4444, extension 42296Nataly.Laflamme@crchudequebec.ulaval.ca
2705, boulevard Laurier
R-4720
Québec, Québec
Canada G1V 4G2 - Muckle, GinaAxis directorHôpital Saint-Sacrement+1 418-525-4444, extension 81972gina.muckle@crchudequebec.ulaval.ca
1050, Chemin Sainte-Foy
J1
Québec, Québec
Canada G1S 4L8 - Pouliot, MarcAxis directorCHUL+1 418-525-4444, extension 46105+1 418-654-2765marc.pouliot@crchudequebec.ulaval.ca
2705, boulevard Laurier
T1-49
Québec, Québec
Canada G1V 4G2 - Préfontaine, PaulEmployeeCHUL+1 418-525-4444, extension 42296 / 46456paul.prefontaine@crchudequebec.ulaval.ca
2705, boulevard Laurier
T2-50
Québec, Québec
Canada G1V 4G2 - Rioux, NadieEmployeeCHUL+1 418-525-4444, extension 46017Nadie.Rioux@crchudequebec.ulaval.ca
2705, boul. Laurier
T0-08
Québec, Québec
Canada G1V 4G2 - Simard, MartinAxis directorL'Hôtel-Dieu de Québec+1 418-525-4444, extension 15185+1 418-691-5439Martin.Simard@crchudequebec.ulaval.ca
9, rue McMahon
0744-5
Québec, Québec
Canada G1R 2J6
Targeting Systemic Innate Immune Cells as a Therapeutic Avenue for Alzheimer Disease
Journal ArticlePharmacol Rev, 74 (1), 2022.
Structural analysis of the microglia-interneuron interactions in the CA1 hippocampal area of the APP/PS1 mouse model of Alzheimer's disease
Journal ArticleJ Comp Neurol, 530 (9), 2022.
Context-dependent transcriptional regulation of microglial proliferation
Journal ArticleGlia, 70 (3), 2022.
Early monocyte modulation by the non-erythropoietic peptide ARA 290 decelerates AD-like pathology progression
Journal ArticleBrain Behav Immun, 99 , 2022.
Multifocal Cerebral Microinfarcts Modulate Early Alzheimer's Disease Pathology in a Sex-Dependent Manner
Journal ArticleFront Immunol, 12 , 2021.
A Homozygous Deep Intronic Mutation Alters the Splicing of Nebulin Gene in a Patient With Nemaline Myopathy
Journal ArticleFront Neurol, 12 , 2021.
Triggering Innate Immune Receptors as New Therapies in Alzheimer's Disease and Multiple Sclerosis
Journal ArticleCells, 10 (8), 2021.
A founder mutation in the PLPBP gene in families from Saguenay-Lac-St-Jean region affected by a pyridoxine-dependent epilepsy
Journal ArticleJIMD Rep, 59 (1), 2021.
Conditional genetic deletion of CSF1 receptor in microglia ameliorates the physiopathology of Alzheimer's disease
Journal ArticleAlzheimers Res Ther, 13 (1), 2021.
Correction to: Selective Immunomodulatory and Neuroprotective Effects of a NOD2 Receptor Agonist on Mouse Models of Multiple Sclerosis
Journal ArticleNeurotherapeutics, 18 (2), 2021.
Active projects
- Acquisition d’équipements pour les activités de recherche en oncologie de précision au Nouveau Complexe hospitalier, from 2022-03-24 to 2027-03-23
- Chaire de recherche du Canada en neuroimmunologie, from 2023-07-01 to 2030-06-30
- Chercheur d'un jour, from 2023-01-01 to 2025-12-31
- Développement de marqueurs génétiques de maladies rares., from 2016-02-11 to 2024-03-31
- Therapeutic properties of innate immune cells and system for brain diseases, from 2022-04-01 to 2025-03-31
Recently finished projects
- Chaire de recherche du Canada en neuroimmunologie, from 2016-07-01 to 2023-06-30
- Chercheur d'un jour, from 2021-01-01 to 2022-12-31
- Programme de soutien aux organismes de recherche et d'innovation (MESI_CATALIS Volet 2 - Recherche clinique) , from 2020-04-23 to 2022-03-31
- Soutenir les établissements dans l'augmentation de leur capacité en recherche - agir sur la phase de démarrage des projets, Phase 2, from 2020-04-01 to 2022-03-31
- Therapeutic properties of innate immune cells and system for brain diseases., from 2015-07-01 to 2022-06-30