Thursday, October 23, 2025 10/23/2025

FAT cadherins and vascular remodeling

Award Number: R01HL163635
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/15/2022
PERIOD OF PERFORMANCE END DATE: 11/30/2026

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FAT cadherins and vascular remodeling - FAT cadherins and vascular remodeling Vascular remodeling is a critical process in the pathogenesis of major vascular diseases such as atherosclerosis, restenosis, saphenous vein graft occlusion, and transplant-associated arteriosclerosis. Factors that control the activities of vascular smooth muscle cells (SMCs) during vascular remodeling remain incompletely understood. Fat cadherins belong to an ancient family of large, single pass type I transmembrane proteins found throughout Metazoans; conserved functions of these proteins affect cell growth and polarity and span from Drosophila to mammals. The FAT1 cadherin is expressed by SMCs in multiple animal models of vascular disease and in injured human arteries. We have found that inactivation of the Fat1 locus in SMCs permits dramatic increases in proliferation and neointimal formation in a mouse model of vascular injury. Interestingly, the FAT1 molecule undergoes complex processing: while cleavage and translocation of the FAT1 intracellular domain (ICD) to the cell nucleus was reported several years ago, we found an accumulation of FAT1 fragments within mitochondria, wherein these FAT1mito species interact selectively with inner membrane proteins and exert critical regulatory control over oxidative phosphorylation, limiting the activities of respiratory Complexes I and II and inhibiting cell growth. FAT1 also has substantial effects on SMC gene expression, promoting expression of SMC marker genes both in vitro and in vivo; interestingly, the FAT1ICD is also found in the cell nucleus, raising the possibility of more direct involvement in gene regulation. In this project, we will assess how FAT1 signals from different locations within the cell, and assess whether these activities are complementary, oppositional, or overlapping to control SMC phenotype. We will investigate intra- and extracellular sequences in FAT1 and interactions with structurally-related proteins FAT4 and DCHS1 that may control how FAT1 is processed and thereby directed to distinct compartments. To assess relevance to key disease processes in vivo, we will assess how these signaling activities affect vascular remodeling and atherosclerosis in mouse models.


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: 2025 ( Subtotal = $586,008 )
2025	2025	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Cardiovascular Diseases Research	000	3	11/15/2024	NON-COMPETING CONTINUATION	$527,407
2025	2025	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Cardiovascular Diseases Research	001	3	8/18/2025	NON-COMPETING CONTINUATION	$58,601
														Subtotal = $586,008

Issue Date FY: 2024 ( Subtotal = $574,288 )
2024	2024	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Cardiovascular Diseases Research	000	2	11/9/2023	NON-COMPETING CONTINUATION	$527,407
2024	2024	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Cardiovascular Diseases Research	001	2	6/26/2024	NON-COMPETING CONTINUATION	$46,881
														Subtotal = $574,288

Issue Date FY: 2023 ( Subtotal = $619,976 )
2023	2023	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Cardiovascular Diseases Research	000	1	12/9/2022	NEW	$619,976
														Subtotal = $619,976

Grand Total All Awards = $1,780,272

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FAT cadherins and vascular remodeling

Award Number: R01HL163635

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/15/2022

PERIOD OF PERFORMANCE END DATE: 11/30/2026

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