# Notch signaling and adhesion regulation

> **NIH NIH R01** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2021 · $412,500

## Abstract

Project Description and Summary
 The goal of this proposal is to characterize a new mechanism by which the Notch
receptor regulates changes in cell adhesion dynamics. Notch signaling is highly conserved
across the animal kingdom to regulate cell fates during development, and its dysregulation has
been implicated in a variety of vascular inflammatory diseases, developmental abnormalities,
and cancers. Binding of ligand to Notch receptor leads to proteolytic cleavages that release the
intracellular domain (ICD) as a transcriptional activator, and this mechanism has been the
primary focus in describing the role of Notch in development and disease. The investigator has
recently found that shear stress caused by blood flow activates Notch, which in turn leads to
rapid assembly of endothelial cell-cell junctions and heightened barrier function. In this work,
they demonstrated that the transmembrane domain (TMD) left behind after Notch proteolysis
initiates the formation of a cortical signaling complex that is responsible for stimulating junction
assembly. Here, the investigator will identify the components, underlying mechanisms, and
cellular impact of this previously unappreciated non-transcriptional, cortical pathway for Notch
and elucidate the biological contexts in which this pathway is engaged. These objectives will be
achieved through an interdisciplinary program built around three Aims: Specific Aim 1 will be to
define mechanisms underlying the non-canonical cortical Notch signaling pathway. Specific Aim
2 will examine crosstalk between adhesion, force, and the cortical Notch signaling pathway.
Specific Aim 3 will be to explore the extent to which the cortical Notch pathway generalizes to
broader biological contexts. Together, these studies will offer important insights into this new
arm of Notch signaling, and provide a molecular basis for how transcriptional and adhesive
programs might be coordinated by a single receptor.

## Key facts

- **NIH application ID:** 10164623
- **Project number:** 5R01HL147585-03
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** CHRISTOPHER S CHEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $412,500
- **Award type:** 5
- **Project period:** 2019-06-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10164623

## Citation

> US National Institutes of Health, RePORTER application 10164623, Notch signaling and adhesion regulation (5R01HL147585-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10164623. Licensed CC0.

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