# Integrative Approaches for Probing Cell Mechanotransduction in Health and Disease

> **NIH NIH R35** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2021 · $412,500

## Abstract

Project Summary
Notch receptors are mechanically activated transmembrane proteins that play important roles in regulating cell
fate, differentiation, proliferation, adhesion, and many other critical processes. However, the majority of studies
to date have been focused largely on understanding Notch from biochemical and genetic perspectives, and only
recently been explored as a mechanoreceptor. Given the varied roles Notch plays in both normal and pathological
states, it is necessary to formulate an integrated mechano-chemical perspective of Notch signaling and regulation
as such outlook is required to achieve a comprehensive view of this critical pathway. In this project, my lab will
leverage our expertise in chemical probe development and molecular tool design in order to address sharply
focused mechanistic questions regarding Notch mechanotransduction. In order to distinguish our contributions
from those of others, we will pursue a multi-scale understanding of the pathway by combining single molecule
studies and high-resolution imaging with the aim of understanding how the activation of the receptor is coupled
to biomechanical events that occur within the cell. In particular, new correlative light and electron microscopy
will be developed and applied to determine the precise timing and location of events surrounding Notch signal
transduction. In addition, in order to address important questions regarding the source and magnitude of the
external forces that are experienced by cells, we will also create synthetic versions of Notch and apply them as
genetically encoded “tensiometers.” Successful execution of this work will provide deep insights into the synergy
occurring between biochemical and mechanical cues as well as increase our overall understanding of the how
cells sense and interpret mechanical information.

## Key facts

- **NIH application ID:** 10241304
- **Project number:** 5R35GM128859-04
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** John Tuan Ngo
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $412,500
- **Award type:** 5
- **Project period:** 2018-08-23 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241304

## Citation

> US National Institutes of Health, RePORTER application 10241304, Integrative Approaches for Probing Cell Mechanotransduction in Health and Disease (5R35GM128859-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10241304. Licensed CC0.

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