Gonçalo Castelo-Branco

Multiple sclerosis (MS) is a neurological disease characterized by autoimmune attack in the central nervous system, targeting oligodendroglia (OLG), and their myelin, which ensheaths neuronal axons. Environment factors and genetic susceptibility play important roles in the etiology of MS. Immune genes harbors MS risk single nucleotide polymorphisms (SNPs)/variants. Thus, genetic predisposition affecting the adaptive immune system is currently thought to be involved in MS. Despite the extraordinary progress in immune-based therapies for MS, these have limited efficacy in the progression of MS. While OLG are mostly considered as mere passive targets in MS, our research indicates that OLG might have an active role in MS and that risk SNPs/variants might contribute to MS by affecting OLG biology. My research group aims to investigate  the role of OLG in disease etiology and progression in MS. We aim to perform detailed single-cell and spatial mapping of the transcriptomic and epigenomic landscapes of OLG in MS. We will assess functional roles of OLG in MS etiology and progression, by developing humanized models to study OLG biology in neuroinflammation, and by performing functional analysis of candidate MS-risk SNPs in OLG. Combining single-cell/spatial omics, genome-editing and functional assays in humanized mice models of MS will lead to unique insights on the role of OLG and SNPs in MS etiology and progression, and advances in the discovery of novel targets for MS therapies.