Project Grant F32AI197563

Federal Project Grant Summary

New York University School of Medicine received a $153,560 Project Grant from the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855), awarded September 30, 2026, with completion targeted for March 31, 2029. The three-year training plan develops antibody-based therapeutic interventions to address transplant rejection driven by donor-specific antibodies (DSAs) that recognize mismatched human leukocyte antigens (HLAs) on transplanted organs. The project focuses specifically on HLA-DQ mismatches, which represent a major driver of antibody-mediated rejection (AMR) but lack precise targeted treatments.

The grant supports two primary research objectives: Aim 1 involves mapping and characterizing epitopes of anti-HLA-DQ antibodies using yeast-displayed library screening and high-throughput techniques, with structural validation through cryo-electron microscopy (cryo-EM). Aim 2 focuses on engineering recombinant antibodies (rAbs) with Fc-silenced modifications to prevent complement activation and Fc-mediated damage, creating blocking antibodies that repurpose pathogenic DSAs into allograft-protective agents. This approach addresses critical limitations of current immunosuppressive strategies, which rely on global immunosuppression rather than precise targeting and are ineffective in patients with pre-existing DSAs, offering potential therapeutic benefit to both treatment-naive and pre-sensitized transplant recipients.