# Measuring Signaling Pathway Dynamics During Tissue Growth in Hydrogels

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $354,560

## Abstract

Project Summary: The studies herein are inspired by the concept that tumors can no longer be perceived
through enumeration of the genetic mutations within the malignancy. The tumor microenvironment contributes
key signals that influence cancer progression. Our long-term goal is aimed at modulating the local environment
to inhibit disease progression, and these studies are aimed at identifying paracrine signaling that may drive
abnormal growth. While the composition of the surrounding tumor microenvironment has been connected to
disease progression, strategies for identifying the key paracrine factors emanating from the stroma are limited.
Our approach is based on the intersection of secretomics (i.e., derived from RNAseq) with large-scale
measurements using a TRanscriptional Activity CEll aRray (TRACER) to quantify transcription factor (TF) and
micro RNA (miRNA) activity in order to identify key factors and pathways driving the observed phenotype.
Macrophages are the immune cells present at the greatest levels in a primary tumor. The components of the
tumor and its environment determine the phenotype of tumor associated macrophages (TAMs). The propensity
of the TAMs to promote tumor growth and metastasis, or act tumoricidal or tumorostatic, is an oncongenic cell
process that has been termed immune editing. The variable behavior of TAMs as a function of the tumor
properties may contribute to the differential outcomes among patients, and TAMs are being investigated for
their prognostic value. Specific Aim 1 will investigate paracrine communication between cancer cells and TAMs
that can impact the ability of TAMs to promote or inhibit invasive phenotypes. Initial studies will investigate the
bi-directional education of macrophage/monocyte populations and the cancer cells. Subsequently, mammary
epithelial cells or cancer cells will be co-cultured with macrophages of varying phenotypes (pre-infiltrating
monocytes, tissue-resident macrophages, and TAMs) and investigate the evolving communication between the
cells that leads to tumor-promoting or tumor-inhibiting microenvironments. Specific Aim 2 will extend the
TRACER technology to the single cell level (i.e., bioluminescence microscopy) to investigate signaling within
the most invasive cancer cells. Heterogeneity within the tumor population is increasingly appreciated as an
important contributor to the observed cancer phenotype. These studies capture the active TFs/miRNA
associated with invasion, and identify the factors with distinct activity that underlie the differential phenotype of
the invasive cell relative to the non-invasive cells within the population. The ability to capture the dynamic
activity of numerous TF/miRNAs at single cell resolution can be employed to track the cues driving cell fate
decisions, which is not achievable through other methods and provides novel perspectives into cancer biology
and cancer immunology. Finally, we investigate the paracrine signaling and TF/miRNA activity ...

## Key facts

- **NIH application ID:** 10226929
- **Project number:** 5R01CA214384-10
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** JACQUELINE SARA JERUSS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $354,560
- **Award type:** 5
- **Project period:** 2017-08-16 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10226929

## Citation

> US National Institutes of Health, RePORTER application 10226929, Measuring Signaling Pathway Dynamics During Tissue Growth in Hydrogels (5R01CA214384-10). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10226929. Licensed CC0.

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