Single-cell, multi-omic investigation of epicardial adipose and coronary endothelial dysfunction in type 1 diabetes

Active Cooperative Agreement Awarded Last action

Award ID
U01DK142338
Recipient
Awarding agency
Obligated
$2,993,255

Award facts

Completion date 76% complete
Place of performance
La Jolla, CA 92093, USA

Award details come from USAspending.gov.

Description

Abstract
Cardiovascular disease (CVD) is the leading cause of mortality in patients with type 1 diabetes (T1D), driven by complex pathophysiological dysfunctions that remain poorly understood at the cellular and molecular level. Epicardial FAT accumulation and dysfunction have recently emerged as significant contributors to coronary artery disease (CAD) in T1D, potentially by inducing coronary artery endothelial dysfunction through pro-inflammatory adipocytokine secretion. This project utilizes the care-T1D consortium tissue bank to investigate the cellular and molecular dysfunctions in epicardial FAT and coronary vasculature in T1D. Specifically, we hypothesize that T1D induces dysfunction in epicardial adipocytes, causing the release of inflammatory adipocytokines that traffic to coronary endothelial cells disrupting their function. We propose to: 1) comprehensively identify T1D-specific cell states and regulators in epicardial FAT and coronary arteries by performing single cell epigenetic and RNA profiling on care-T1D flash-frozen samples. 2) genetically program "induced" T1D adipocytes in vitro to functionally characterize diabetes-specific adipocyte cellular responses and identify dysregulated adipocytokines. 3) integrate care-T1D coronary vascular profiles with functional genomic perturbations in endothelial cells to define molecular mechanisms of T1D-specific endothelial dysfunction and test identified adipocytokines on endothelial functions such as angiogenesis, adhesion and migration. This research promises to elucidate the cellular mechanisms of CVD in T1D, offering insights into novel therapeutic targets and a genomic atlas of single cell resolution data for future investigation.

Transactions

Action Obligated Date
Amendment $991,069
Amendment $0
Amendment $0
Amendment $993,436
Original award $1,008,750

Subawards

Subrecipient Amount Awarded
Brigham & Womens Hospital Inc. Mod: 358,000.00 11/13/2025 Mod: -60,636.82 11/13/2025 Sub: 358,000.00 03/04/2025 The Gupta Lab will lead all activities in Aim 3 of this proposal: Integrate… $655,363

Quick answers

Who received award U01DK142338?

U01DK142338 was awarded to University Of California, San Diego by National Institute of Diabetes and Digestive and Kidney Diseases (National Institutes of Health) on September 18, 2024.

How much is award U01DK142338 worth?

$2,993,255 has been obligated on U01DK142338.

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