Federal Project Grant Award Summary

Cleveland Clinic Lerner College of Medicine of Case Western Reserve University received a $608,840 Project Grant from the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855), awarded July 7, 2026, with completion targeted for June 30, 2031. The research investigates the metabolic drivers underlying donor-specific antibody (DSA) development in solid organ transplantation, with particular focus on how obesity and overweight conditions alter B cell metabolism to increase DSA production through extrafollicular plasma cell pathways rather than traditional germinal center responses. This research addresses a critical gap in transplantation immunology, as DSA emergence—even in non-HLA-sensitized recipients—doubles the likelihood of graft loss within five years, and currently no FDA-approved treatment exists for antibody-mediated rejection (ABMR).

The project leverages high-fat diet mouse models to examine how obesity-associated metabolic changes in B cells, specifically those regulated by mTORC1 signaling, preferentially drive DSA production through extrafollicular pathways that are less responsive to conventional T cell-mediated immunosuppressive therapies. By elucidating these metabolic mechanisms, the research aims to identify novel therapeutic targets to prevent or reduce DSA development and improve long-term graft survival in transplant recipients. The work is conducted at Cleveland Clinic's Cleveland, Ohio facility.