Federal Grant Award Summary

The National Institute of Allergy and Infectious Diseases (NIAID) awarded Boston Children's Hospital a $889,904 Project Grant under the Allergy and Infectious Diseases Research program (CFDA 93.855) effective June 10, 2026, with completion targeted for May 31, 2031. This research initiative will deliver mechanistic understanding of how the integrin α4β7 protein mediates leukocyte rolling and firm adhesion during extravasation, with particular focus on improving therapeutic interventions for ulcerative colitis and Crohn's disease. The research will produce high-resolution cryo-electron microscopy (cryo-EM) structures of unliganded α4β7 and its complexes with ligands and medically relevant antibodies, revealing ligand recognition mechanisms, conformational changes upon ligand binding, and structural specializations that enable rolling adhesion—ultimately informing improved drug design strategies to enhance the limited efficacy of the currently approved antibody therapeutic vedolizumab.

The project will generate peer-reviewed scientific data and structural biology products characterizing how therapeutically relevant antibodies modulate α4β7 function, with investigation into the kinetics of ligand binding and dissociation, conformational change pathways, and the role of actin cytoskeleton activation in the transition from rolling to firm adhesion. These research deliverables will advance understanding of integrin biology and contribute to the translational science objectives of NIAID's infectious disease and immunologic disorder research portfolio, with potential applications to inflammatory bowel disease treatment development.