Project Grant R01HL187387

The National Heart, Lung, and Blood Institute awarded Rhode Island Hospital $712,858 on August 20, 2026, under the Cardiovascular Diseases Research program (CFDA 93.837) to investigate the role of DELTEX E3 ubiquitin ligase 3L (DTX3L) in sepsis-induced insulin resistance and cardiac dysfunction.

The research examines whether muscle-specific DTX3L mediates ubiquitination and degradation of HDAC4 as a mechanism to mitigate septic cardiac depression and insulin resistance. The project uses CRISPR/CAS9 gene editing to develop muscle-specific DTX3L knockout genetic mouse models to test this hypothesis. Sepsis induces rapid insulin resistance and cardiac dysfunction that drive multi-organ failure and high mortality; current interventions lack mechanism-based approaches targeting these two critical events. Prior work by the principal investigator identified that DTX3L declines in muscle during sepsis and that muscle-targeted DTX3L silencing enhances inflammatory cytokine release, and found DTX3L forms a unique association with HDAC4 in cardiac muscle.

Work is performed in Providence, Rhode Island. The period of performance extends from August 20, 2026, through April 30, 2030. This is a Project Grant, the standard assistance type for NHLBI research funding.