# Roles of mechanotransduction in organ regeneration and fibrosis

> **NIH NIH R35** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2023 · $99,180

## Abstract

Project Abstract
Environmental biomechanical cues play a critical role in cell growth and functional homeostasis.
Many human diseases, such as organ fibrosis, cardiovascular diseases, and cancers, have been
associated with aberrant biomechanical cues that promote disease progression. However, how
cells sense and propagate biomechanical cues into biochemical signals, a process known
as mechanotransduction, is poorly understood. In particular, the precise signaling transduction
mechanisms and transcriptional outputs of mechanotransduction remain unknown. Unveiling the
roles and signaling cascades of mechanotransduction is important for understanding fundamental
development and disease mechanisms and for advancing therapeutic strategies.
I have been developing a research program, supported by R35GM142504, to elucidate the roles
and mechanisms of mechanotransduction in tissue growth control and disease development, with
a current focus on how mechanotransduction controls regeneration and fibrosis during organ
injury, repair, and carcinogenesis. The main challenge in understanding mechanotransduction in
these disease contexts is the lack of knowledge of mechanotranscriptomes and signaling
cascades that are triggered by a combination of force-, cell-, and microenvironment-specific
factors. In this proposal, I aim to answer 3 main questions to advance our understanding in the
field: (i) what role does mechanotransduction play in regulating cellular functions
and transcriptomes, particularly in the context of tissue repair and fibrosis? (ii) what are the
signaling cascades that connect plasma membrane mechanosensors to mechanotranscriptomes?
(iii) how do biomechanical cues and wound-healing signals integrate to control cellular functions
and transcriptomes?
I will use endothelial cells and the liver as my main models to study these questions, as they are
classical models for studying mechanotransduction and tissue repair, respectively. We will
characterize endothelial mechanotransductionfor its roles in liver regeneration and fibrosis mainly
using (i) in vitro or ex vivo bioengineered models with human primary endothelial cells, and (ii) in
vivo mouse models of liver injury.
We propose to use an Avatar Duo System for the in vitro and ex vivo experiments in the original
proposal. This system can save us from the efforts of in-house manufacturing several devices to
perform the work in the original proposal, more efficiently enabling us to conduct the experiments
proposed in R35GM142504 under the biomechanical and biophysical environments that
resemble physiological and pathophysiological conditions.
I expect that this new instrument will allow my research program to more efficiently advance the
fundamental understanding of mechanotransduction in normal and diseased contexts, thus
helping identify new druggable targets from mechano-signaling cascades for organ fibrosis and
other diseases.

## Key facts

- **NIH application ID:** 10798540
- **Project number:** 3R35GM142504-03S1
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** ZHIPENG MENG
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $99,180
- **Award type:** 3
- **Project period:** 2021-07-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10798540

## Citation

> US National Institutes of Health, RePORTER application 10798540, Roles of mechanotransduction in organ regeneration and fibrosis (3R35GM142504-03S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10798540. Licensed CC0.

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