# Integrated Imaging Tools for Intercellular Chemokine Signalling

> **NIH NIH R61** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $207,850

## Abstract

Chemokines and their G-protein coupled receptors (GPCRs) are key mediators of intercellular
signaling between cancer cells and multiple stromal cell types. Cancer cell proliferation, local
invasion, systemic metastasis, recruitment of immune cells and angiogenesis all are regulated by
spatial and temporal dynamics of chemokines. The central role of chemokines in tumor biology
has made them an attractive target for therapies designed to inhibit or enhance chemokine
signaling. However, much of the complex biochemistry of chemokines remains to be discovered,
due to the technical challenges of tracing their presence and function in living systems.
Chemokines are effective at signaling at very low levels, and their spatial distribution is complex
due to their ability to bind to cell surfaces and extracellular matrix. Furthermore, internalization of
chemokines by GPCRs and scavenger receptors shape local chemokine gradients by
sequestering and degrading chemokines. Experimental evidence and computational modeling by
our lab show that short-range, steep local gradients of chemokine CXCL12 over distances of a
single cell most effectively drive signaling and chemotaxis through receptor CXCR4. To enable
transformative studies of chemokines and ultimately advance applications of drugs targeting
chemokines in cancer, we propose to develop a new suite of quantitative molecular imaging tools
to measure the spatial and temporal dynamics of chemokine distribution, association, and
signaling in hundreds of single cells. These tools will allow us to measure cell signaling patterns
during chemotaxis and identify potential mechanisms underlying intercellular heterogeneity in
responses to chemokines. We will 1) Generate an integrated, multiplexed bioluminescence and
fluorescence microscopy toolbox for single-cell imaging of extracellular and intracellular steps in
chemokine signaling; and 2) Test our chemokine imaging technology as a generalizable,
quantitative approach applicable to patient-derived cells. We will uniquely combine dynamic,
single-cell bioluminescence and fluorescence microscopies technologies to measure numerous
molecular events cells use to convert chemokine inputs into signaling outputs and chemotaxis.
We will couple our multiplexed imaging readouts with advanced image processing methods to
generate high-dimensional quantitative data sets needed for basic studies of chemokines and
integration with other large-scale data. Our innovative imaging tools will allow an unprecedented
view of chemokine gradients and heterogeneity of cellular responses in complex environments.
This technology will transform investigations of chemokines in cancer and advance ongoing
efforts to target chemokines for therapy.

## Key facts

- **NIH application ID:** 10903923
- **Project number:** 5R61CA281657-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Gary D Luker
- **Activity code:** R61 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $207,850
- **Award type:** 5
- **Project period:** 2023-08-09 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10903923

## Citation

> US National Institutes of Health, RePORTER application 10903923, Integrated Imaging Tools for Intercellular Chemokine Signalling (5R61CA281657-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10903923. Licensed CC0.

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