# Imaging nanoscale chromatin folding in early carcinogenesis

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $456,914

## Abstract

PROJECT ABSTRACT
This application is to evaluate the potential of a super-resolution microscopy system to image disrupted
nanoscale chromatin folding as an early event in carcinogenesis and explore its potential to improve cancer
risk stratification. Abnormal chromatin structure is among the most universal characteristics of tumor cells and
has been used for clinical cancer diagnosis for two centuries. However, due to the diffraction-limited resolution
of conventional light microscopy, only microscale structural abnormalities can be observed. As a result, cells
undergoing early stages of malignant transformation often appear normal. Such limitation in image resolution
has compromised our ability to accurately risk-stratify precursor lesions or distinguish aggressive from indolent
forms. Recent advances in super-resolution fluorescence nanoscopy now enable us to image molecular-level
chromatin structure down to a resolution of ~20-30 nm. Our group recently improved the throughput and
robustness in stochastic optical reconstruction microscopy (STORM)-based super-resolution microscopy and
enabled robust imaging of chromatin folding on the most widely used clinical samples. Built upon our
preliminary studies that revealed a significant and gradual disruption of nanoscale chromatin folding in early
carcinogenesis, this project will first further confirm the disrupted chromatin folding that accompanies
carcinogenesis and identify their molecular characteristics and functional consequences. Second, we will
optimize the workflow of super-resolution imaging system, sample preparation and image analysis to enable
efficient and reproducible analysis of nanoscale chromatin folding in clinical tissue samples. We will also
validate our finding of disrupted chromatin folding in patients with various colorectal precursor lesions and
cancer. Third, we will evaluate the potential of imaging nanoscale chromatin folding to in patients with
colorectal adenomatous polyps. This study will establish the scientific basis and underlying molecular profile of
disrupted nanoscale chromatin folding in early carcinogenesis, opening a new avenue for risk stratification,
facilitating the development and evaluation of new preventive strategies.

## Key facts

- **NIH application ID:** 10071252
- **Project number:** 1R01CA254112-01
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Yang Liu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $456,914
- **Award type:** 1
- **Project period:** 2020-08-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10071252

## Citation

> US National Institutes of Health, RePORTER application 10071252, Imaging nanoscale chromatin folding in early carcinogenesis (1R01CA254112-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10071252. Licensed CC0.

---

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