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Probing sex differences in myocardial fibrosis at multiple length scales using biomaterials

Award Number: DP2HL173948
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/05/2023
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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Probing sex differences in myocardial fibrosis at multiple length scales using biomaterials - PROJECT SUMMARY My proposed research for the NIH Director’s New Innovator Award seeks to determine how biological sex modulates myocardial fibrosis and develop innovative models of sex-specific tissue remodeling using advanced biomaterial technologies. Myocardial fibrosis, or the aberrant remodeling of extracellular matrix in the heart, is a common outcome of several cardiac pathologies, including ventricular pressure overload, myocardial infarct, hypertension, cardiac inflammation, and/or genetic cardiomyopathies, all of which can lead to heart failure. Even though standard-of-care medications have been useful to help relieve heart failure symptoms, clinically effective therapeutics to halt and reverse myocardial fibrosis progression are not available. Biological sex is a potent modulator of myocardial fibrosis. For example, clinical studies have established that patients experiencing diastolic dysfunction and develop heart failure with preserved ejection fraction (HFpEF) are 2.84-fold more likely to be female. Unfortunately, the historical dependence on male-biased disease models for understanding myocardial fibrosis has left a significant gap in understanding female-specific heart failure mechanisms, causing significant health disparities in treatment outcomes for female patients. To change course, our laboratory will develop sex-specific cardiac fibrosis models and determine paths toward sex-specific therapies to halt disease progression and move toward equitable treatment outcomes. My proposal outlines an innovative research program to identify how X-chromosome dosage in cardiac myofibroblasts gives rise to sex differences in myocardial fibrosis after injury. Our three project thrusts centralize around the hypothesis that X-chromosome dosage regulates (1) myofibroblast activation signaling networks in cardiac fibroblasts, (2) extracellular matrix remodeling after myocardial injury, and (3) inflammation during myocardial fibrosis in females. Understanding sex-specific mechanisms of myocardial fibrosis may inform paths toward sex-specific treatment protocols and significantly impact clinical practice. If successful, the proposed research will significantly and broadly advance our fundamental understanding of sex-specific biology in myocardial fibrosis and other cardiovascular diseases.


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 = $960,000 )
2026	2026	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Trans-NIH Research Support	000	2	8/19/2026	EXTENSION WITH OR WITHOUT FUNDS	$960,000
														Subtotal = $960,000

Issue Date FY: 2023 ( Subtotal = $1,422,000 )
2023	2023	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DRIVE	LA JOLLA	CA	92093	SAN DIEGO	USA	Trans-NIH Research Support	000	1	9/5/2023	NEW	$1,422,000
														Subtotal = $1,422,000

Grand Total All Awards = $2,382,000

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Probing sex differences in myocardial fibrosis at multiple length scales using biomaterials

Award Number: DP2HL173948

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/05/2023

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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