# Biophysical regulation of genome architecture in meniscus cells

> **NIH NIH K01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $126,495

## Abstract

Project Summary
 My long-term career goal is to become an independent investigator and a leader in the fields of stem
cell engineering and regenerative medicine, with a focus on orthopedic applications. In particular, I will
contribute to improving cell therapeutic strategies for the repair and regeneration of dense connective tissues,
including meniscus and tendon. Meniscus injury and damage is the most common of knee injury, with over 1.8
million meniscal injuries being treated in the EU and the US each year. However, meniscal injuries have limited
repair and little is known regarding meniscus cell phenotype and mechano-regulation with development and
during disease/after injury. It is clear that the dynamic spatio-temporal organization of the genome is a central
determinant of gene expression and cell differentiation, and so it will be important to understand how 3D
genome architecture changes with meniscus development or in response to exogenous chemo-mechanical
cues to develop better cell therapeutic strategies. The goals of my proposed K01 work is to elucidate how
genome organization of cells within the knee meniscus change with development and degeneration, in both
animal and human cells. In addition, I will determine how chemo-mechanical cues (e.g. substrate stiffness and
mechanical loading) that change during development or degeneration regulate genome organization in
meniscus cells. Through the work, I will acquire expertise in 3D genome-architecture and techniques to
quantify chromatin fiber organization using super-resolution stochastic optical reconstruction microscopy
(STORM). I will also evaluate changes in epigenetic status using ChIP-PCR, and will evaluate gene expression
using the single cell-based fluorescent in situ hybridization (FISH) in meniscus cells as a function of tissue
development or after injury and in response to mechanical input. Aim 1 will identify chromatin organization and
histone modifications at the nanoscale during meniscus development and degeneration using super-resolution
stochastic optical reconstruction microscopy (STORM) imaging and genome wide analyses including ChIP-
PCR and RNA-FISH. Aim 2 will determine whether biophysical cues can establish and/or restore meniscus
specific genome organization, epigenetic landscape, and expression patterns in differentiating and
degenerative meniscus cells. This study will inform us to advance diagnostic and therapeutic strategies for
dense connective tissue repair and regeneration. Importantly, this K01 award will allow me to improve my
scientific knowledge and techniques, and will further provide important preliminary data for independent grant
applications.

## Key facts

- **NIH application ID:** 9953425
- **Project number:** 1K01AR077087-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Su Chin Heo
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $126,495
- **Award type:** 1
- **Project period:** 2020-05-15 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9953425

## Citation

> US National Institutes of Health, RePORTER application 9953425, Biophysical regulation of genome architecture in meniscus cells (1K01AR077087-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9953425. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*