Project Grant P01HL187163

The National Heart Lung and Blood Institute awarded New York University a project grant of $2,567,368 on September 1, 2026, under the Cardiovascular Diseases Research program (CFDA 93.837) to investigate macrophage signaling, cell-intrinsic and cell-cell communications, and ischemic injury in diabetes through the RAGE/DIAPH1 axis.

The research focuses on mitochondrial dysfunction in cardiac and skeletal muscle cells driven by RAGE ligands in diabetes and hypoxia/ischemia conditions. Project 1 (P1) will test the hypothesis that the RAGE-DIAPH1-mitofusin 2 (MFN2) signaling hub mediates mitochondrial-driven pathogenic mechanisms exacerbating inflammation, cell death, and cardiac dysfunction in diabetes and ischemia-reperfusion injury via cell-intrinsic and cell-cell communication mechanisms. Project 2 (P2) will examine how RAGE ligands activate DIAPH1 and its intracellular interactome, including MFN2 and cofilin1 (CFL1), to induce mitochondrial dysfunction and release of mitochondrial damage-associated molecular patterns that amplify downstream dysfunction. The research will explore depot- and cue-dependent molecular reprogramming that exacerbates ischemic injury in diabetes and the role of DIAPH1 interaction with MFN2 and CFL1 in trained immune responses.

The award funds research performance in New York, New York 10016 with a period of performance through June 30, 2031. This is assistance funding characterized as a project grant, the principal assistance type for NIH hypothesis-driven basic and translational research.