# Research Test-Bed Unit

> **NIH NIH U54** · NORTHWESTERN UNIVERSITY · 2022 · $577,203

## Abstract

Research Test-Bed Unit: PROJECT SUMMARY
The overall goal of the U54 Northwestern University Center for Chromatin Nanoimaging in Cancer (NU-CCNIC)
is to develop and deploy a multi-scale chromatin nanoimaging platform together with molecular analyses and
computational modeling to characterize chromatin structure and transcriptional patterns associated with the
cancer stem cell (CSC) and chemoresistance phenotype. The immediate application of the proposed studies will
be ovarian cancer, a malignancy of unmet need. It has been speculated that CSCs represent the reservoir from
which recurrent, chemotherapy-resistant tumors arise. The key biological question addressed by this Center is
whether reprogramming of the transcriptome through epigenetic and chromatin organization-regulated
mechanisms leads to significant transcriptional plasticity, which is critical for CSCs to withstand and survive
stressors in the tumor environment, driving tumor initiation and progression. As part of NU-CCNIC, the Research
Test-Bed Unit (RTB) will provide source materials for the nanoimaging technologies developed by the
Technology Development Unit (TECH). These resources include cells and tissues at various transition points
between stem cell and non-stem cell phenotypes and between chemotherapy-sensitive and resistant states. The
studies conducted by the RTB will test the applicability of the Nanoscale Chromatin Imaging and Analysis (nano-
ChIA) platform and provide feedback to optimize its use. In addition, the RTB will perform state-of-the-art
computational genomic analyses of CSCs and chemotherapy-resistant cells, including single-cell mRNA
sequencing and genome mapping (e.g., Hi-C, ATAC-sequencing and ChIP-sequencing). The specific
objectives of this unit are: 1) To identify CSC-specific epigenomic features and 3D chromatin packing
conformations by integrating genome-wide maps of chromatin accessibility, contact frequency and gene
expression networks with high resolution nano-scale chromatin imaging features. 2) To identify whether the
transition to a chemotherapy-resistant state promotes stemness-like chromatin packing and conformation. Locus
specific epigenetic manipulations will be coupled with high resolution imaging technologies to investigate
resistant-state specific 3D chromatin packing and its relation to the CSC state. 3) To discover how global
epigenome manipulations induced by small enzymatic inhibitors block stemness and chemo-resistance through
alterations of chromatin packing. In all, the integrated interrogation of cancer through chromatin nanoimaging
methods (TECH) and genome-wide mapping (RTB) will discover how transcriptional plasticity of CSCs and
chemo-resistant cancer cells is regulated. The project is at the forefront of the field by using highly innovative
molecular and nanometer-scale chromatin imaging technologies to better understand the relationship between
higher level chromatin structure and key drivers of stemness and chemo-resistance in...

## Key facts

- **NIH application ID:** 10375271
- **Project number:** 1U54CA268084-01
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Daniela E Matei
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $577,203
- **Award type:** 1
- **Project period:** 2021-12-10 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10375271

## Citation

> US National Institutes of Health, RePORTER application 10375271, Research Test-Bed Unit (1U54CA268084-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10375271. Licensed CC0.

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