Olivia Thomas

Multiple sclerosis (MS) is common among young adults. Serious neurological deficits evolve. There are efficient treatments, but with risks. Progressive disease ensues despite treatments. Development of precise treatments is hampered by insufficient knowledge of the pathogenesis. Autoimmunity to the central nervous system (CNS) tissue is a likely mechanism, perhaps triggered by molecular mimicry to pathogens like Epstein Barr virus (EBV), along with other lifestyle/environmental factors. They interact with MS disposing genes. We will: 1) determine how molecular mimicry between MS associated pathogens may lead to and perhaps perpetuate MS. 2) Establish the relevance of viral cross-reactive immune responses to central nervous system (CNS) tissue antigens by extensively characterizing their frequency, function and pathogenicity. 3) Identify novel autoantigenic targets of pathogenic immune responses, not necessarily resulting from pathogen molecular mimicry. 4) Test the CNS inflammatory pathogenic potential of selected mimicry antigens, and other novel autoantigens in mouse models experimental autoimmune encephalomyelitis (EAE). 5) Use spatial transcriptomics, to localize target autoantigens and their expression in MS brains/lesions, healthy human brains and in EAE. 6) The Epstein Barr virus1, EBNA1 molecule has a central role in molecular mimicry and viral replication. We therefore will construct a mouse transgenic model for immune and therapeutic studies.