Federal Project Grant Award Summary

The University of Arizona received a $562,733 Project Grant from the National Heart, Lung, and Blood Institute (NHLBI) under the Cardiovascular Diseases Research program (CFDA 93.837), awarded July 6, 2026, with completion targeted for May 31, 2027. The award funds research to develop small molecule therapeutics for heart failure by inhibiting tristetraprolin (TTP), a protein that regulates cardiac metabolism and inflammatory responses. The research leverages a novel approach to disrupt TTP's binding to CNOT1 (C-terminal binding domain), which mediates messenger RNA decay. This strategy aims to improve cardiac function through enhanced fatty acid oxidation and branched-chain amino acid metabolism while avoiding systemic inflammatory side effects that occur with global TTP inhibition.

The project builds on preliminary findings demonstrating that cardiac-specific deletion of TTP improves cardiac function following heart failure induction in mouse models. By selectively disrupting TTP's interaction with the CCR4-NOT complex rather than eliminating TTP entirely, the research seeks to achieve therapeutic benefit without the autoimmune complications observed in global TTP knockout animals. The work utilizes published crystal structures of CNOT1 binding to guide compound development, positioning this research to advance understanding of cardiac metabolic regulation and identify druggable targets for heart failure treatment.