# Determining the Role of Discoidin Domain Receptor 2 in the Pathogenesis of Pancreatic Ductal Adenocarcinoma

> **NIH NIH F31** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $5,128

## Abstract

PROJECT SUMMARY/ABSTRACT
Pancreatic Ductal Adenocarcinoma (PDA) is an aggressive and lethal cancer characterized by a collagen-
dense microenvironment. The overproduction of collagen and the subsequent fibrosis that follows has been
studied in recent years; however, the impact of this prominent feature in PDA is left inconclusive. Extended
pancreatic injury, as seen in chronic inflammation (pancreatitis), results in a pro-fibrotic collagen-rich response
that promotes an initial process called acinar-ductal metaplasia (ADM). ADM is an event in which the epithelial
acinar cells transdifferentiate into duct-like cells with progenitor characteristics and is thought to be a precursor
to PDA in the presence of oncogenic Kras. Therefore, investigating the interactions between the acinar cells
with the collagen-dense stromal compartment may offer a point of intervention in the activation of ADM and the
gradual development of PDA.
New preliminary evidence suggests Discoidin Domain Receptor 2 (DDR2), a unique receptor tyrosine kinase
(RTK) that signals in response to binding to its collagen ligand may play a role in the development of PDA. To
date, the activation of DDR2 and the subsequent intracellular signaling that follows has not been studied in the
context of pancreatic diseases. DDR2 is a probable candidate in the study of PDA due to the dominant
collagen overproduction and its nature as an RTK that is amenable to drug intervention. With these facts in
place, this proposal will test the hypothesis that DDR2 activation is necessary to promote signaling between
tumor cells and stroma that is required for the progression and metastasis of PDA The following specific aims
will: 1.) Test the hypothesis that DDR2 in tumor cells is required for the development of PDA. 2.) Test the
hypothesis that DDR2 activation in tumor cells and fibroblasts is required for the invasion and metastasis of
PDA. To accomplish these specific aims, human cell lines and genetically engineered mouse models will be
used to perform the appropriate in vitro and in vivo experiments to study PDA progression and metastasis.
The results from these innovative studies will establish the role of DDR2 in the progression of PDA with the
overall future aim of identifying DDR2 as a diagnostic and therapeutic target for patients. The proposed
studies in this application follow the objectives of the Ruth L. Kirschstein National Research Service Award
(NRSA) for Individual Predoctoral Fellowship (Parent F31) in determining novel methods and generating
scientific ideas to promote the advancement of cancer research.

## Key facts

- **NIH application ID:** 10215381
- **Project number:** 5F31CA220966-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Jeanine Ruggeri
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $5,128
- **Award type:** 5
- **Project period:** 2018-08-01 → 2020-06-23

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10215381

## Citation

> US National Institutes of Health, RePORTER application 10215381, Determining the Role of Discoidin Domain Receptor 2 in the Pathogenesis of Pancreatic Ductal Adenocarcinoma (5F31CA220966-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10215381. Licensed CC0.

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