Federal Grant Award Summary

Baylor College of Medicine received a $798,854 Project Grant award from the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855), effective June 16, 2026, through May 31, 2031. The project focuses on developing brain-penetrant molecular glue degraders targeting VAV1 (Vav guanine nucleotide exchange factor 1), a key signaling protein implicated in T and B lymphocyte activation and multiple sclerosis (MS) pathogenesis. The research aims to deliver optimized VAV1 molecular glue degraders with enhanced potency, brain penetration, and favorable pharmacokinetic properties through advanced computational modeling and medicinal chemistry approaches.

The award supports three primary research objectives: (1) optimization of lead VAV1 molecular glue degraders for improved efficacy and CNS penetration; (2) evaluation of optimized degraders in preclinical mouse models of MS (experimental autoimmune encephalomyelitis) to assess disease amelioration, reduced CNS inflammation, and demyelination; and (3) investigation of structure-activity relationships for a novel VAV1 degron motif to advance understanding of molecular glue-mediated protein degradation mechanisms. This research addresses significant unmet medical needs in MS treatment by developing therapeutics capable of targeting both enzymatic and scaffolding functions of VAV1 to mitigate neuroinflammation, potentially delivering novel therapeutic candidates and expanded knowledge applicable to other challenging disease targets.