Federal Project Grant Award Summary

Vanderbilt University Medical Center received a $1.77 million Project Grant from the National Heart, Lung, and Blood Institute (NHLBI) under the Cardiovascular Diseases Research program (CFDA 93.837), awarded June 10, 2026, with completion targeted for March 31, 2030. The grant funds research into TBX4-driven pulmonary hypertension (PH), the second most common cause of heritable pulmonary arterial hypertension (PAH), which predominantly affects pediatric patients. The research aims to elucidate molecular mechanisms underlying TBX4 mutations and develop therapeutic intervention strategies.

The project delivers integrated research products through three primary research tools and multiple investigative aims. Researchers will employ chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) to identify direct binding targets of the TBX4 transcription factor, utilize a postnatal TBX4 knockout mouse model that phenocopies human disease, and conduct single-cell RNA-seq analysis to map cellular changes. Specific deliverables include testing the hypothesis that TBX4 loss derepresses RGS5 and impairs angiogenesis through PI3K inhibition in pericytes via pericyte-specific knockouts (Aim 1), examining TBX4 roles in fibroblasts and smooth muscle through cell-specific knockouts (Aim 2), and validating therapeutic targets through pharmacologic PI3K induction and siRNA knockdown of RGS5 in precision-cut lung slices (Aim 3). These research products are designed to identify novel therapeutic targets for treating TBX4-driven PAH.