Grant Award Summary

The University of Pennsylvania received a $635,421 Project Grant from the National Heart, Lung, and Blood Institute (NHLBI) under the Cardiovascular Diseases Research program (CFDA 93.837), effective May 1, 2026, through January 31, 2030. This research project investigates the regulatory mechanisms by which the transcription factor RUNX1 (Runt-Related Transcription Factor 1) controls inflammatory responses in granulocyte-monocyte progenitors and neutrophils. The funded research will produce scientific outputs including mechanistic understanding of how RUNX1 restrains type I interferon signaling, characterization of epigenomic signatures in patient-derived cells, and identification of neutrophil subpopulation differences relevant to Familial Platelet Disorder with Predisposition for Myeloid Malignancy (FPDMM).

The project deliverables encompass both preclinical discoveries using mouse models and translational research validating findings in human samples from FPDMM patients. Specifically, the research will yield data on RUNX1's regulation of inflammatory cytokine and chemokine production, the relationship between elevated type I interferon signaling and retroelement accessibility, the impact of inflammation on innate immune training, and comparative epigenomic and functional analysis of neutrophils from patient populations. These research outputs are intended to advance understanding of how inflammation contributes to clonal hematopoiesis and leukemia risk in RUNX1-mutant individuals, potentially informing therapeutic strategies for inflammatory and immune complications associated with FPDMM.