# An intra-vital metabolic microscope to reveal the mechanisms of radiation resistance in  head and neck carcinomas

> **NIH NIH P20** · UNIVERSITY OF KENTUCKY · 2022 · $303,995

## Abstract

PROJECT SUMMARY
Given the clinical importance of radio-resistance in head and neck squamous cell cancer (HNSCC),
understanding how radio-resistant tumors rewire their metabolic pathways and vascular network to escape
radiotherapy (RT) is critical towards developing strategies to eliminate residual tumor cells and/or prevent
subsequent recurrence. Currently, no techniques are available to provide a systems level approach to image the
major axes of metabolism and the associated vasculature at a spatial resolution that can elucidate the modulation
of cancer cell metabolism or vascular reprogramming in vivo. Our technological goal is to create innovative
solutions in microscopy, automated algorithms and experimental strategies to image tumor metabolism, vascular
function and architecture at a spatial resolution that allows for visualization of primary tumors, residual disease
and recurrence following RT to facilitate the understanding of tumor biology and function, assessment of
recurrence risk and design of therapies to mitigate residual disease and/or recurrence altogether in pre-clinical
models. Our technological approach fills an important gap that exists between in vitro cell studies and whole-
body imaging, and is complementary to metabolomics and immunohistochemistry. The Specific Aims of this
proposal are to develop a portable multi-parametric microscope that combines structured illumination microscopy
and dark field microscopy in a re-emission geometry to image key metabolic and vascular endpoints
simultaneously (Specific Aim 1); and use the technology with in vivo HNSCC orthotropic models to test the
novel hypothesis that RT-induced hypoxia-inducible factors (HIF-1α and HIF-2α) expression and subsequent
changes in metabolism/vasculature underlie HNSCC radio-resistance (Specific Aim 2). This proposal will set
the foundation for translating our technology to patient-derived xenograft models that have been shown to
faithfully recapitulate many of the micro-environmental features of patient tumors, allowing us to move our
technique forward towards translational pharmaceutical research.

## Key facts

- **NIH application ID:** 10271869
- **Project number:** 2P20GM121327-06
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Caigang Zhu
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $303,995
- **Award type:** 2
- **Project period:** 2017-03-01 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10271869

## Citation

> US National Institutes of Health, RePORTER application 10271869, An intra-vital metabolic microscope to reveal the mechanisms of radiation resistance in  head and neck carcinomas (2P20GM121327-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10271869. Licensed CC0.

---

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