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Imaging nanoscale chromatin folding in early carcinogenesis

早期致癌过程中纳米级染色质折叠的成像

基本信息

批准号：
10605199
负责人：
Yang Liu
金额：
$ 6.75万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-01 至 2023-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10605199
关键词：
Adenocarcinoma Affect Archives Biological Cells ChIP-seq Characteristics Chromatin Chromatin Structure Clinical Clinical Management Colonoscopy Colorectal Colorectal Adenoma Colorectal Cancer Colorectal Neoplasms Computer software DNA Damage DNA biosynthesis Data Development Distal Early Diagnosis Evaluation Event Fluorescence Fluorescence Microscopy Formalin Gene Expression Genes Genome Image Image Analysis Indolent Intestines Lesion Location Maintenance Malignant - descriptor Malignant Neoplasms Microscopy Molecular Molecular Profiling Nanoscopy Nobel Prize Normal tissue morphology Ontology Optics Outcome Paraffin Embedding Pathology Pathway interactions Patient Care Patients Preparation Prevention strategy Preventive Protocols documentation Recurrence Reproducibility Resolution Risk Sampling Structural defect System Techniques Tissue Embedding Tissue Sample adenoma biological research cancer diagnosis cancer risk carcinogenesis clinically significant high risk high throughput analysis imaging system improved innovation intestinal tumorigenesis light microscopy molecular imaging mouse model nanoscale neoplastic cell novel premalignant reconstruction research clinical testing risk prediction risk stratification screening success superresolution imaging superresolution microscopy transcriptome sequencing tumor tumor growth ultra high resolution

项目摘要

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.

项目摘要