NIH grant: Mechanisms of antigen-specific T cell activation in MOGAD (1K08AI199129-01)

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NIH grant 1K08AI199129-01: Mechanisms of antigen-specific T cell activation in MOGAD
Institute: {'code': 'AI', 'abbreviation': 'NIAID', 'name': 'National Institute of Allergy and Infectious Diseases', 'admin_org_id': '12500003', 'admin_funding_url': ''}. PI: Carson E Moseley. Award: $190836.
Start: 2026-06-18T00:00:00.
PROJECT SUMMARY / ABSTRACT
The overarching goal of this application is to train Dr. Carson E. Moseley, MD, PhD, who is a clinical neurologist
and a research immunologist, to become an independent investigator studying and treating neuroimmunologic
disorders. Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a recently
described, severe, neuroinflammatory syndrome of the central nervous system (CNS) with no approved
therapies. Although MOG-specific antibodies helped define the disease, MOG antibodies alone are not clearly
pathogenic and our understanding of MOGAD immunopathology is limited. CD4+ T cells are a dominant
lymphocyte population in MOGAD lesions, yet the targets of T cell responses to MOG and how T and B cells
interact to drive pathogenic immune response in MOGAD are unknown. This proposal uses a complementary
approach of human and mouse immunology along with new technologies in T cell repertoire mapping and
genome editing to dissect MOG-specific CD4+ T cell responses in MOGAD. Additionally, it will use new models
to investigate how B cells promote pathogenic T cell differentiation and select pathogenic T cell receptors.
The proposed training plan involves mentored training, seminars, formal learning, and advising to ensure
completion of the proposed research and Dr. Moseley’s career development. He will train at UCSF, which is an
outstanding institute for research and environment for physician-scientists. He will receive training in human
immunology and CRISPR-based gene editing technologies. He will be mentored by Dr. Scott Zamvil, a leader in
identifying antigen-specific T cell responses in neuroimmunologic disorders, and co-mentored by Dr. Alexander
Marson, an expert in CRISPR gene editing to understand lymphocyte function. This application will provide Dr.
Moseley with the long-term skills needed to become an independent investigator leading efforts to study and
treat neuroimmunologic disorders.

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