Principal Investigator

Thomas D
Awardee Organization

University Of Michigan At Ann Arbor
United States

Fiscal Year
Activity Code
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

Early detection of colorectal cancer in the traditional and serrated pathways

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 peptidebased 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.


  • Shirazi A, Sahraeibelverdi T, Lee M, Li H, Yu J, Jaiswal S, Oldham KR, Wang TD. Miniature side-view dual axes confocal endomicroscope for repetitive in vivo imaging. Biomedical optics express. 2023 Jul 26;14(8):4277-4295. doi: 10.1364/BOE.494210. eCollection 2023 Aug 1. PMID: 37799693
  • Wu X, Chen CW, Jaiswal S, Chang TS, Zhang R, Dame MK, Duan Y, Jiang H, Spence JR, Hsieh SY, Wang TD. Near-Infrared Imaging of Colonic Adenomas In Vivo Using Orthotopic Human Organoids for Early Cancer Detection. Cancers. 2023 Sep 29;15. (19). PMID: 37835489
  • Li G, Lee M, Chang TS, Yu J, Li H, Duan X, Wu X, Jaiswal S, Feng S, Oldham KR, Wang TD. Wide-field endoscope accessory for multiplexed fluorescence imaging. Scientific reports. 2023 Nov 9;13(1):19527. PMID: 37945660
  • Lee M, Li H, Birla MB, Li G, Wang TD, Oldham KR. Capacitive Sensing for 2-D Electrostatic MEMS Scanner in a Clinical Endomicroscope. IEEE sensors journal. 2022 Dec 15;22(24):24493-24503. Epub 2022 Oct 27. PMID: 37497077
  • Li T, Chang TS, Shirazi A, Wu X, Lin WK, Zhang R, Guo JL, Oldham KR, Wang TD. Scaling down the dimensions of a Fabry-Perot polymer film acoustic sensor for photoacoustic endoscopy. Journal of biomedical optics. 2024 Jan;29(Suppl 1):S11514. Epub 2024 Jan 2. PMID: 38169937