# Integrative Single-Cell Atlas of Host and Microenvironment in Colorectal Neoplastic Transformation

> **NIH NIH U2C** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2021 · $211,782

## Abstract

PROJECT SUMMARY: Overall Colorectal cancer (CRC) is among the top three most prevalent cancers in
global incidence and mortality. Most of these cancers develop from pre-cancerous adenomas. Colonoscopy is
currently the most effective CRC prevention strategy. However, colonoscopy may fail to prevent carcinoma in
as many as 24% of cases, is less effective at preventing proximal CRCs, is expensive for health care systems
to implement, carries economic and psychosocial burdens for patients, and can be complicated by bleeding,
perforation, and other adverse events. There is an unmet need to develop new preventive strategies and risk
stratification models to address these and other issues. By analysis of whole human tissue, seminal work from
Bert Vogelstein and co-workers demonstrated that CRC develops from an accumulation of genetic events as
tumors evolve from small to large adenomas and, eventually, to cancers. More recently, our group reported the
first comprehensive proteogenomic characterization of CRC, which also was from a bulk analysis of whole
tissue Despite this wealth of data on CRC, we believe that the ability to provide the most effective precision
diagnostics and preventive strategies can only be achieved with single-cell analysis. Through such a single-cell
analysis, we propose to map spatial relationships across the spectrum of normal colon, early polyps, and late
adenomas, including their unique stromal and microbial microenvironments. Aim 1: To construct a pre-cancer
atlas of colorectal adenoma progression that depicts the spatial landscape of the tumor ecosystem, including
the stroma and biofilm-associated microbiome, using single-cell (sc)RNA-seq, whole exome sequencing,
multiplex immunofluorescence (MxIF), and species-specific bacterial fluorescence in situ hybridization (FISH).
Aim 2: To integrate the activities and data from the Biospecimen, Tissue Characterization and Data Analysis
Units for the prospective standardized collection and analysis of colorectal tissue, associated biospecimens,
and related clinical and epidemiological data from 1,800 participants undergoing colonoscopy or surgical
resection. Aim 3: To disseminate the pre-cancer atlas, related biospecimens, primary data sets and analytical
tools to the Human Tumor Atlas Network (HTAN), the broader scientific community, and the lay public. To
accomplish these aims, we have assembled a highly interactive and established team of investigators with
complementary expertise (epidemiologists, gastroenterologists, pathologists, surgeons, systems biologists,
bioinformaticians, cancer biologists, immunologists, and biofilms/infectious disease experts). To further
optimize our novel methodologies for application to the prospectively collected samples from 1,800 atlas
participants, we will leverage our existing large repository of colorectal adenomas and supporting
biospecimens, generated and curated through an ongoing epidemiological project through 3 cycles of the
Vanderbilt GI...

## Key facts

- **NIH application ID:** 10380489
- **Project number:** 3U2CCA233291-01S1
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Robert J. Coffey
- **Activity code:** U2C (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $211,782
- **Award type:** 3
- **Project period:** 2018-09-20 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10380489

## Citation

> US National Institutes of Health, RePORTER application 10380489, Integrative Single-Cell Atlas of Host and Microenvironment in Colorectal Neoplastic Transformation (3U2CCA233291-01S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10380489. Licensed CC0.

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