Federal Project Grant Award Summary

The University of Pittsburgh has received a $764,245 Project Grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847), effective June 1, 2026 through March 31, 2031. The award funds research into branched chain amino acid (BCAA) metabolism and related inborn errors of metabolism (IEMs), specifically addressing the cellular mechanisms underlying BCAA metabolic disorders and developing novel therapeutic interventions.

The research delivers three primary products: (1) visualization of BCAA metabolism enzyme organization within mitochondria using high-resolution cryo-electron tomography to characterize disruptions in patient-derived cells; (2) development and testing of a novel therapeutic compound (PMA010) designed to reduce pathogenic lysine propionylation and normalize protein succinylation in cells from patients with propionic acidemia (PA) and methylmalonic acidemia (MMA); and (3) targeted metabolic interventions to improve cellular bioenergetics in patients with these organic acidemias. The research is conducted at the University of Pittsburgh's Pittsburgh, Pennsylvania facility and represents investigator-initiated biomedical research aimed at improving understanding and treatment of metabolic disease mechanisms.