# Super-Resolution Imaging of Higher-Order Heterochromatin Structure for Early Detection of Lung Carcinogenesis

> **NIH NIH R21** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $222,122

## Abstract

PROJECT SUMMARY/ABSTRACT
Lung cancer is the leading cause of cancer-related death in the United States. Overall, patients diagnosed with
early-stage lung cancer have a much better prognosis. Cigarette smoking is the major cause of lung cancer
and screening for lung cancer is currently recommended for high-risk current and former smokers. Compared
with nonsmokers, smokers have an almost 30-fold increased risk of developing lung cancer. Unfortunately,
despite significant efforts, early detection of lung cancer remains sub-optimal with conventional approaches
suffering from high false-positive rates or limited sensitivity. Improved understanding of the early events
underlying smoking-related lung cancer development is crucial to the identification of new biomarkers and
targets for early detection and prevention. Further, new methods that detect those early events in lung cancer
development in a non-invasive and cost-effective manner with high sensitivity and specificity are urgently
needed. Recent advances in super-resolution microscopy revolutionize the field of optical microscopy and offer
a new ability to visualize molecular structure at nanometer resolution that is invisible under a conventional light
microscope. We propose an innovative approach to adapt super-resolution microscopy to improve the early
detection of lung cancer. Our approach is built upon our recent discovery that chromatin folding becomes
gradually fragmented in early lung carcinogenesis, even when cells still appear normal under conventional light
microscope. Our ultimate goal is to detect such nanoscale chromatin “misfolding” in bronchial cells present in
sputum to improve early detection of lung cancer. In this project, we will first establish disrupted nanoscale
chromatin folding as an early event in lung carcinogenesis utilizing a mouse model of carcinogen-induced lung
adenocarcinoma as well as existing well-annotated human lung tissue specimens (Aim 1). In addition, we will
evaluate the feasibility of super-resolution imaging of nanoscale chromatin “misfolding” for early detection of
lung cancer using existing sputum samples and data from the Pittsburgh Lung Screening Study, a community-
based research cohort of current and ex-smokers, screened with low-dose computed tomography and followed
for lung cancer (Aim 2).

## Key facts

- **NIH application ID:** 10435645
- **Project number:** 1R21CA259787-01A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Yang Liu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $222,122
- **Award type:** 1
- **Project period:** 2022-03-15 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10435645

## Citation

> US National Institutes of Health, RePORTER application 10435645, Super-Resolution Imaging of Higher-Order Heterochromatin Structure for Early Detection of Lung Carcinogenesis (1R21CA259787-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10435645. Licensed CC0.

---

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