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Defining the role of Cartilage Oligomeric Matrix Protein (COMP) in Heart Failure Pathogenesis

Award Number: F32HL186720
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 03/01/2027
PERIOD OF PERFORMANCE END DATE: 02/29/2028

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Defining the role of Cartilage Oligomeric Matrix Protein (COMP) in Heart Failure Pathogenesis - PROJECT SUMMARY/ABSTRACT Heart failure remains a leading cause of morbidity and mortality globally. Heart failure pathophysiology is characterized by cellular, molecular, and structural remodeling of the heart which leads to progressive cardiac dysfunction. The diverse cell types that comprise the adult heart are central to mediating this remodeling process. Signaling cues from various cell populations act via paracrine mechanisms to alter the cardiac microenvironment, and promoting disease progression. Modulating these signaling pathways offers a promising but incompletely explored therapeutic avenue. This proposal seeks to define the mechanisms of a previously uncharacterized fibroblast-derived signaling ligand, Cartilage Oligomeric Matrix Protein (COMP), in heart failure pathogenesis. Preliminary data show that COMP expression is tightly correlated with disease severity, and that COMP signaling directly alters cardiomyocyte physiology and activates pathological gene expression programs. In vivo Comp overexpression is sufficient to induce cardiac dysfunction. To define the role of COMP in heart failure, this project applies multidisciplinary approaches integrating cell and organ physiology, stem cell–based disease models, mouse molecular genetics, and transcriptional/epigenomic assays across three specific aims: i) Define the molecular pathways by which COMP induces cardiomyocyte remodeling and dysfunction; ii) Assess the role of COMP in vivo by modeling increased circulating COMP and using conditional knockout approaches; and iii) Elucidate the regulatory mechanisms that govern stress-induced COMP expression by fibroblasts. This work will define the specific role of COMP as a paracrine effector in heart failure and establish a broader framework for how stress-induced secreted ligands drive disease progression, enabling future therapeutic targeting of these pathways. The postdoctoral training will be conducted under the primary mentorship of Dr. Michael Alexanian, with support from a multidisciplinary team of co-mentors at the University of California, San Francisco and the Gladstone Institutes. The institutional environment, extensive resources, and strong commitment to trainee development provide an exceptional setting for the proposed research and training goals.


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 = $86,824 )
2026	2026	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Cardiovascular Diseases Research	000	1	9/4/2026	NEW	$86,824
														Subtotal = $86,824

Grand Total All Awards = $86,824

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Defining the role of Cartilage Oligomeric Matrix Protein (COMP) in Heart Failure Pathogenesis

Award Number: F32HL186720

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 03/01/2027

PERIOD OF PERFORMANCE END DATE: 02/29/2028

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