# Fluid shear stress mechanotransduction at endothelial cell-cell junctions

> **NIH NIH R01** · YALE UNIVERSITY · 2023 · $84,568

## Abstract

Summary of the funded parent grant
The goal of our project “Fluid shear stress mechanotransduction at endothelial cell-cell junctions” is to
elucidate mechanisms by which vascular endothelial cells sense fluid shear stress (FSS) from blood flow,
which is a major determinant of blood vessel embryonic development, adult physiology and multiple diseases
including atherosclerosis and vascular malformations. While a great many pathways and genes that respond to
FSS have been identified, major questions about fundamental molecular mechanisms by which cell convert
FSS into biochemical information remain unanswered. The project is based on published and preliminary data
showing that cell-cell junctions are a major site of shear stress mechanotransduction via a complex of
membrane proteins consisting of the homophilic adhesion receptors PECAM-1 (hereafter PECAM) and VE-
cadherin, and the receptor tyrosine kinases VEGF receptor 2 and 3. More recently, we have identified the
adhesion GPCR latrophilin1 (ADGRL2) as another junctional protein that appears to be the initial upstream
trigger that activates the junctional pathway [1]. This pathway is highly relevant to vascular disease as
polymorphisms in PECAM-1 are linked to atherosclerosis, while ADGRL2 is linked to hypertension and
ischemic stroke.

## Key facts

- **NIH application ID:** 10688712
- **Project number:** 3R01HL155543-03S1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Chenxiang Lin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $84,568
- **Award type:** 3
- **Project period:** 2021-01-27 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10688712

## Citation

> US National Institutes of Health, RePORTER application 10688712, Fluid shear stress mechanotransduction at endothelial cell-cell junctions (3R01HL155543-03S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10688712. Licensed CC0.

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