# Early detection of colorectal cancer in the traditional and serrated pathways

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $345,230

## Abstract

Project Summary/Abstract
 Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide. Conventional
colonoscopy with white light illumination frequently misses pre-malignant lesions that are either flat or subtle in
appearance. CRC arises from either the traditional or serrated pathways in >95% of all known cases.
Development of imaging biomarkers expressed in these two pathways can improve methods for early CRC
detection. Successful completion of the aims will result in proof-of-concept for a targeted imaging strategy to
improve the effectiveness of colonoscopy for early CRC detection.
 Peptide monomers specific for cMet and peroxiredoxin-1 will be optimized and arranged in a heterodimer
configuration. These molecular targets are over expressed by pre-malignant lesions that arise from the
traditional and serrated pathways, respectively. IRDye800 will be used as a near-infrared fluorescence label.
Specific binding will be validated with cells in vitro and human colon specimens ex vivo using known
antibodies.
 A flexible fiber endoscope accessory will be developed to image the heterodimer in vivo. The scalable
optical design scans a low numerical aperture beam at large angles to achieve diffraction-limited resolution
over a wide field-of-view. A miniature scanner will be developed based on parametric resonance with mixed
stiffness-softening dynamics to deflect the beam at large angles. The compact form factor allows the
instrument to be passed forward through the biopsy channel of standard medical endoscopes.
 Patient-derived organoids will be used to validate specific binding by the peptide heterodimer and verify
the flexible fiber endoscope in vivo. These colonoids will be developed from traditional adenomas, sessile
serrated adenomas, and normal mucosa, and will be implanted orthotopically in immunocompromised mice.
These pre-malignant lesions appear endoscopically with flat and subtle features. Target expression levels and
genetic heterogeneity are representative of pre-malignant lesions seen in the clinic.
 This collaborative work will be led by PI TD Wang, an expert in development and validation of peptide-
based imaging agents. KR Oldham is an authority in microsystems-based scanning technologies, and JR
Spence is an expert in development of primary human organoid cultures.

## Key facts

- **NIH application ID:** 10244933
- **Project number:** 5R01CA249851-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Thomas D Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $345,230
- **Award type:** 5
- **Project period:** 2020-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10244933

## Citation

> US National Institutes of Health, RePORTER application 10244933, Early detection of colorectal cancer in the traditional and serrated pathways (5R01CA249851-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10244933. Licensed CC0.

---

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