Project Grant R01HL182780

The National Heart, Lung, and Blood Institute awarded The Methodist Hospital Research Institute $755,573 on August 21, 2026, under the Cardiovascular Diseases Research program (CFDA 93.837) to investigate the role of the muscle-specific E3 ligase TRIM55 in autoimmune myocarditis pathogenesis.

The research uses monogenic autoimmune myocarditis models based on TREX1 deficiency to examine how innate immune responses shape disease development. The work combines in vitro studies using human fibroblasts from Aicardi-Goutieres syndrome patients carrying TREX1R114H/R114H mutations—which exhibit elevated type I interferon production—with in vivo studies using TREX1-deficient mice that spontaneously develop autoimmune myocarditis. Through small-interfering RNA screening, the research identified TRIM55 as a critical driver of the disease cascade; TRIM55 knockout in TREX1-deficient mice completely rescued lethal autoimmune myocarditis phenotypes, including reduced cardiac inflammation, autoantibody production, and mortality. The study also examines spermine metabolism and its relationship to cytosolic mitochondrial DNA and cell death in cardiomyocytes as mechanisms underlying TRIM55-driven pathogenesis.

Performance occurs in Houston, Texas, with work concluding May 31, 2030. This is a Project Grant, an assistance type supporting investigator-initiated research under the NHLBI's competitive research funding program.