Federal Grant Award Summary

Cincinnati Children's Hospital Medical Center received a $445,500 Project Grant from the National Institute on Aging (Aging Research program, CFDA 93.866) awarded on May 15, 2026, with a completion date of April 30, 2028. This award funds a research project investigating proteomic identification of nuclear rupture-associated proteins in laminopathy hearts, with a focus on understanding mechanisms underlying LMNA-related dilated cardiomyopathy (LMNA-DCM). The research deliverables include systematic identification of proteins recruited to nuclear rupture sites using proximity labeling techniques (BioID) in cardiomyocyte-specific LMNA-knockout mice, validation of candidate protein localization and association with ruptured versus repaired nuclei, and functional characterization of selected proteins through in vivo depletion studies to assess their roles in cellular outcomes following nuclear rupture.

The project addresses a critical gap in understanding age-associated nuclear envelope dysfunction by identifying and characterizing proteins that regulate divergent cellular responses to nuclear rupture—ranging from pathological consequences such as gene expression defects and DNA damage to endogenous repair mechanisms. The research utilizes three rupture-associated protein markers (BANF1, LEMD2, and catalytically inactive cGAS) as experimental baits to discover novel protein interactions at nuclear rupture sites. Findings from this investigation are intended to enable development of therapeutic strategies to prevent nuclear rupture or promote repair mechanisms in cardiac tissue affected by LMNA-DCM and potentially other age-associated conditions involving nuclear envelope integrity.