# Dissection of in situ myeloid signaling using image-guided synthetic control

> **NIH NIH DP2** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $2,520,000

## Abstract

A major goal of systems biology has been to comprehend how molecular circuitry governs information
processing and decision-making in multicellular communities. A growing and largely descriptive single-cell
atlas of tissues and pathologies has begun providing rich insight into the composition and spatial organization
of microenvironments, yet it remains a challenge to understand cause-and-effect relationships from such
data. How does the signaling state of one cell affect that of its neighbors? This simple question is complicated
by reaction/diffusion transport in tissue, feedback loops based on cellular response to signaling, and dynamic
cell migration. Despite this complexity, understanding principles of multi-scale intercellular communication
promises to be a key component in designing cellular- and signaling-based therapies. Unfortunately, it has
been difficult to directly parse signal propagation in tissue because technological gaps have limited our ability
to manipulate and monitor cell behavior in situ within native disease microenvironments.#
Our proposal addresses these questions by leveraging recent advances in in vivo imaging, nanotechnology,
and synthetic biology to generate a framework for image-guided manipulation, real-time monitoring, and
systems-level analysis of signal propagation within microenvironmental niches. As an initial application, we
will use this framework to understand how myeloid polarization signaling influences the tumor
microenvironment in metastatic ovarian cancer. We focus in particular on monocyte-derived dendritic cells
and macrophages, since they are highly implicated in drug resistance, they are therapeutically manipulated
via targeted drugs or adoptive cell therapies, and it remains unclear how their signaling across the spectrum
of pro- and anti-inflammatory states can spread to neighboring cells over space and in time. Although this
project will yield fundamental insights into myeloid signaling propagation, we also aim to extend image-
guided genetic reprogramming to translationally-relevant modalities with potential therapeutic application.
The novel integration of technologies to achieve these goals promises to be flexible and useful for diverse
biological applications where myeloid cells play a role, in cancer and beyond.#

## Key facts

- **NIH application ID:** 9997419
- **Project number:** 1DP2CA259675-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Miles A Miller
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,520,000
- **Award type:** 1
- **Project period:** 2020-09-04 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9997419

## Citation

> US National Institutes of Health, RePORTER application 9997419, Dissection of in situ myeloid signaling using image-guided synthetic control (1DP2CA259675-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9997419. Licensed CC0.

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