# A Multimodal 3D Atlas of Colorectal Cancer Across Ages of Onset

> **NIH NIH U01** · VANDERBILT UNIVERSITY · 2024 · $1,063,411

## Abstract

PROJECT SUMMARY
We propose the construction of a three-dimensional (3D) multimodal molecular atlas of colorectal cancer
(CRC) across different ages of onset of the disease. We aim to address the emerging clinical challenge
of rising early-onset CRC cases by exploring molecular differences between early-onset and later-onset
CRCs. We hypothesize that aberrant interactions between the carcinogenic microbes, tumor metabolic
niche, and the tumor microenvironment lead to accelerated transitions of precancerous cell states to
malignant states. Our atlas will focus on spatially mapping transitions from precancerous to cancerous
components within the same tumor, utilizing a "phylogeographic" mapping approach to create
individualized and global progression trajectories between tumor subtypes (early onset CRCs, later-onset
microsatellite stable CRCs, later-onset microsatellite unstable CRCs). We employ cutting-edge
technologies, such as customized spatial transcriptomics, co-detection by indexing highly multiplexed
immunofluorescence microscopy, untargeted imaging mass spectrometry, and histological and
autofluorescence imaging, to comprehensively characterize CRC tissue at various molecular levels and
spatial scales. We employ a 3D multimodal strategy by reconstructing volumes from interleaving serial
tissue sections evaluated by different technologies. Paired whole exome sequencing and single-cell
RNA-sequencing data will anchor our spatial analyses to our previous Human Tumor Atlas Network
(HTAN) data. We leverage our previous success in building colorectal atlases within the HTAN and
ensure that data are released for open-access use to the research community. We have a strong team
with expertise in genomic profiling, multi-omic spatial analysis, biostatistics, and artificial intelligence. Our
proposal emphasizes our team's extensive track record in CRC research, with active programs in CRC,
gut epithelial biology, CRC microbiome, epidemiology, and pathology. Our goal is to provide
unprecedented insights into the genetic, transcriptomic, metabolomic, microbial, and architectural
features of CRC in a spatially resolved manner to better understand CRCs across various age groups.

## Key facts

- **NIH application ID:** 10994992
- **Project number:** 1U01CA294527-01
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Ken S Lau
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,063,411
- **Award type:** 1
- **Project period:** 2024-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10994992

## Citation

> US National Institutes of Health, RePORTER application 10994992, A Multimodal 3D Atlas of Colorectal Cancer Across Ages of Onset (1U01CA294527-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10994992. Licensed CC0.

---

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