Project Grant R01DK148345

The National Institute of Diabetes and Digestive and Kidney Diseases awarded Benaroya Research Institute At Virginia Mason $907,235 on September 1, 2026, under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847) to define the origins and effector function of avβ6-specific autoantibodies in ulcerative colitis.

The research dissects the repertoire, biochemical activity, and pathogenic functions of avβ6-specific autoantibodies in ulcerative colitis, integrating patient-based and mechanistic model systems. Nearly all ulcerative colitis patients produce high-titer autoantibodies to the epithelial integrin avβ6, which precede clinical disease by up to ten years and associate with worse outcomes. The avβ6 integrin is the dominant epithelial activator of transforming growth factor beta-1, a master regulator of mucosal immune balance and epithelial barrier repair. Preliminary findings demonstrate that a subset of patient autoantibodies block avβ6-mediated TGF-β1 activation, functioning as de facto anti-cytokine antibodies, while other antibodies bind without blocking catalytic activity. The research tests whether multiple mechanisms—including blocking TGF-β1 activation, conformational locking, or Fc-dependent effector functions—converge to destabilize epithelial-immune cross-talk and promote inflammation.

Performance occurs in Seattle, Washington. The period of performance runs from September 1, 2026, through May 31, 2030. This is a Project Grant, the assistance type under the NIDDK extramural research program for investigator-initiated biomedical research.