U54HL170326
Cooperative Agreement
Overview
Grant Description
Sex differences in cardiometabolic health and disease - overall summary
The objective of our score on "Sex Differences in Cardiometabolic Health and Disease" is to identify factors that determine sex-specific cardiometabolic disease risk, which may lead to better diagnosis and treatment for both sexes. A unique feature of our program is the investigation of sex differences from multiple perspectives, including effects of estrogen, of XX vs. XY sex chromosome genes, and of genetic variation among individuals.
Our program consists of three research projects and three cores, and will use preclinical mouse models, human induced pluripotent stem cell lines (iPSCs), and existing human population datasets (genomic, transcriptomic, proteomic, and metabolomic) to translate findings from our model systems to humans.
Project 1, "Epigenetic Sex Determinants of Cardiometabolic Disease and Prevention," will build on our identification of X and Y chromosome genes that influence sex differences in both the development of diet-induced obesity and susceptibility to adverse effects of statin drugs. We will elucidate the role of three X-Y histone demethylase genes in epigenetic sex differences in mouse adiposity and human adipocyte differentiation. We will also identify the epigenetic determinants of sex-biased statin adverse effects on mitochondrial function.
Project 2, "Gene-by-Sex Interactions in Heart Failure with Preserved Ejection Fraction (HFPEF)," seeks to understand the mechanisms underlying increased prevalence of HFPEF in women compared to men. Using a "systems genetics" approach and a panel of genetically distinct mouse strains, the goals are to understand sex differences in HFPEF traits at the molecular level, including the role of gonadal hormones and sex chromosomes, and to create sex-specific biologic networks that can be generalized to humans. Recent findings implicate sex differences in the mitochondrial enzyme, ACSL6, as causal for HFPEF, and further studies will characterize the role of mitochondrial dysfunction in HFPEF.
Project 3, "The Impact of Estrogen Receptor Alpha on Cardiomyocellular Metabolism and Health," will test the hypothesis that estrogen receptor alpha action in cardiomyocytes impacts mitochondrial metabolism, cardiac tissue integrity, and heart function. Findings with unique cardiomyocyte estrogen receptor alpha knockout or overexpression mouse models will then be integrated with human data in collaboration with our human translational bioinformatics core.
The human translational bioinformatics core will serve as a hub for computational analyses to translate findings from the three projects for association and relevance to cardiometabolic traits in humans using existing large human genetic and -omics datasets.
The career enhancement core will foster research in sex differences in metabolism by administering a pilot & feasibility grant program, and will educate researchers and students about SABV through courses, hands-on laboratory 'bootcamp,' and a library of SABV videos.
The administrative core will ensure effective leadership and management of this score.
The objective of our score on "Sex Differences in Cardiometabolic Health and Disease" is to identify factors that determine sex-specific cardiometabolic disease risk, which may lead to better diagnosis and treatment for both sexes. A unique feature of our program is the investigation of sex differences from multiple perspectives, including effects of estrogen, of XX vs. XY sex chromosome genes, and of genetic variation among individuals.
Our program consists of three research projects and three cores, and will use preclinical mouse models, human induced pluripotent stem cell lines (iPSCs), and existing human population datasets (genomic, transcriptomic, proteomic, and metabolomic) to translate findings from our model systems to humans.
Project 1, "Epigenetic Sex Determinants of Cardiometabolic Disease and Prevention," will build on our identification of X and Y chromosome genes that influence sex differences in both the development of diet-induced obesity and susceptibility to adverse effects of statin drugs. We will elucidate the role of three X-Y histone demethylase genes in epigenetic sex differences in mouse adiposity and human adipocyte differentiation. We will also identify the epigenetic determinants of sex-biased statin adverse effects on mitochondrial function.
Project 2, "Gene-by-Sex Interactions in Heart Failure with Preserved Ejection Fraction (HFPEF)," seeks to understand the mechanisms underlying increased prevalence of HFPEF in women compared to men. Using a "systems genetics" approach and a panel of genetically distinct mouse strains, the goals are to understand sex differences in HFPEF traits at the molecular level, including the role of gonadal hormones and sex chromosomes, and to create sex-specific biologic networks that can be generalized to humans. Recent findings implicate sex differences in the mitochondrial enzyme, ACSL6, as causal for HFPEF, and further studies will characterize the role of mitochondrial dysfunction in HFPEF.
Project 3, "The Impact of Estrogen Receptor Alpha on Cardiomyocellular Metabolism and Health," will test the hypothesis that estrogen receptor alpha action in cardiomyocytes impacts mitochondrial metabolism, cardiac tissue integrity, and heart function. Findings with unique cardiomyocyte estrogen receptor alpha knockout or overexpression mouse models will then be integrated with human data in collaboration with our human translational bioinformatics core.
The human translational bioinformatics core will serve as a hub for computational analyses to translate findings from the three projects for association and relevance to cardiometabolic traits in humans using existing large human genetic and -omics datasets.
The career enhancement core will foster research in sex differences in metabolism by administering a pilot & feasibility grant program, and will educate researchers and students about SABV through courses, hands-on laboratory 'bootcamp,' and a library of SABV videos.
The administrative core will ensure effective leadership and management of this score.
Funding Goals
TO FOSTER HEART AND VASCULAR RESEARCH IN THE BASIC, TRANSLATIONAL, CLINICAL AND POPULATION SCIENCES, AND TO FOSTER TRAINING TO BUILD TALENTED YOUNG INVESTIGATORS IN THESE AREAS, FUNDED THROUGH COMPETITIVE RESEARCH TRAINING GRANTS. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, USE SMALL BUSINESS TO MEET FEDERAL RESEARCH AND DEVELOPMENT NEEDS, FOSTER AND ENCOURAGE PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY SOCIALLY AND ECONOMICALLY DISADVANTAGED PERSONS, AND INCREASE PRIVATE-SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, FOSTER TECHNOLOGY TRANSFER THROUGH COOPERATIVE R&D BETWEEN SMALL BUSINESSES AND RESEARCH INSTITUTIONS, AND INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL R&D.
Grant Program (CFDA)
Awarding / Funding Agency
Place of Performance
Los Angeles,
California
900958347
United States
Geographic Scope
Single Zip Code
Related Opportunity
Analysis Notes
Amendment Since initial award the total obligations have increased 497% from $747,581 to $4,462,990.
Los Angeles University Of California was awarded
Sex Differences in Cardiometabolic Health: Investigating Factors
Cooperative Agreement U54HL170326
worth $4,462,990
from National Heart Lung and Blood Institute in September 2018 with work to be completed primarily in Los Angeles California United States.
The grant
has a duration of 9 years 9 months and
was awarded through assistance program 93.837 Cardiovascular Diseases Research.
The Cooperative Agreement was awarded through grant opportunity Specialized Centers of Research Excellence (SCORE) on Sex Differences (U54 Clinical Trial Optional).
Status
(Ongoing)
Last Modified 7/25/25
Period of Performance
9/20/18
Start Date
6/30/28
End Date
Funding Split
$4.5M
Federal Obligation
$0.0
Non-Federal Obligation
$4.5M
Total Obligated
Activity Timeline
Subgrant Awards
Disclosed subgrants for U54HL170326
Transaction History
Modifications to U54HL170326
Additional Detail
Award ID FAIN
U54HL170326
SAI Number
U54HL170326-2912416480
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Public/State Controlled Institution Of Higher Education
Awarding Office
75NH00 NIH National Heart, Lung, and Blood Institute
Funding Office
75NH00 NIH National Heart, Lung, and Blood Institute
Awardee UEI
RN64EPNH8JC6
Awardee CAGE
4B557
Performance District
CA-36
Senators
Dianne Feinstein
Alejandro Padilla
Alejandro Padilla
Budget Funding
| Federal Account | Budget Subfunction | Object Class | Total | Percentage |
|---|---|---|---|---|
| Office of the Director, National Institutes of Health, Health and Human Services (075-0846) | Health research and training | Grants, subsidies, and contributions (41.0) | $749,999 | 50% |
| National Heart, Lung, and Blood Institute, National Institutes of Health, Health and Human Services (075-0872) | Health research and training | Grants, subsidies, and contributions (41.0) | $747,581 | 50% |
Modified: 7/25/25