Serge Rivest

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 33,700 citations and H factor 100.

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. Our ultimate goal is to develop a new medication based on new ligands that target the receptor NOD2 in innate immune cells to prevent and treat both diseases.

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.