Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Proteomic identification of nuclear rupture-associated proteins in laminopathy hearts

Award Number: R21AG098113
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/15/2026
PERIOD OF PERFORMANCE END DATE: 04/30/2028

Group Awards By:

View Award Description

Proteomic identification of nuclear rupture-associated proteins in laminopathy hearts - Project Summary The nuclear envelope can rupture in various age-associated conditions, including cellular senescence, neurodegenerative disorders, cancer, myocardial infarction, and premature aging. Nuclear rupture can lead to pathological consequences, such as gene expression defects, DNA damage, and innate immune activation, or instead be resolved through endogenous repair. How these divergent outcomes are regulated remains unknown. This is a critical gap in our understanding, because uncovering the underlying mechanisms could enable strategies to prevent rupture or promote repair. We hypothesize that proteins recruited to nuclear rupture sites – most of which remain unidentified – regulate these cellular responses. To test this hypothesis, we will systematically identify proteins recruited to nuclear rupture sites. Our disease model is LMNA-related dilated cardiomyopathy (LMNA-DCM), a fatal heart disease. LMNA encodes Lamin A/C, a nuclear lamina protein that maintains nuclear envelope integrity. We have developed cardiomyocyte-specific Lmna-knockout mice (LmnaCKO) as a model of LMNA-DCM and observed frequent nuclear rupture in the heart, as in the patient hearts. In Aim 1, we will identify proteins recruited to nuclear rupture sites in LmnaCKO cardiomyocytes using in-vivo BioID. As baits, we will use three rupture-associated proteins that we found to accumulate at rupture sites in LmnaCKO hearts: namely, BANF1, which binds DNA at rupture sites; LEMD2, a transmembrane protein implicated in membrane repair; and catalytically inactive cGAS (icGAS), which marks both ruptured and repaired nuclei. In Aim 2A, we will validate the localization of candidate proteins identified in Aim 1 and determine whether they preferentially associate with ruptured or repaired nuclei. In Aim 2B, we will assess the functional roles of select candidates by depleting them in vivo and measuring their effects on nuclear rupture and repair frequencies. If successful, this project will yield the first systematic identification of nuclear rupture-associated proteins in any cellular context. By defining the “rupture proteome”, this project has the potential to uncover novel regulators of nuclear rupture and repair, offering the potential therapeutic targets for LMNA-DCM and other age-related conditions characterized by nuclear envelope rupture.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $445,500 )
2026	2026	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Aging Research	000	1	5/11/2026	NEW	$445,500
														Subtotal = $445,500

Grand Total All Awards = $445,500

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Proteomic identification of nuclear rupture-associated proteins in laminopathy hearts

Award Number: R21AG098113

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/15/2026

PERIOD OF PERFORMANCE END DATE: 04/30/2028

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer