# Dissecting the role of Notch signaling in the pancreatic cancer microenvironment.

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $521,831

## Abstract

Project Summary/Abstract
Pancreatic cancer is marked by an immunosuppressive tumor microenvironment contributing to the overall
therapeutic resistance seen in this deadly malignancy. Although Notch signaling is integral in the progression of
pancreatic neoplasia, its role in the establishment and maintenance of the immunosuppressive tumor
microenvironment is unclear. The long-term goal is to define the role of intercellular signaling pathways like Notch
in the treatment resistance in pancreatic cancer. The overall objective of this application is to define how Notch
regulates myeloid and, as a consequence, T cell polarization in the pancreatic tumor microenvironment to
regulate its immunosuppressive nature. The central hypothesis of the application is that Notch serves as one of
the key regulatory pathways promoting the establishment of immunosuppressive myeloid and exhausted or
anergic T cell populations. The rationale for this proposal is that understanding the mechanistic basis and effects
of Notch signaling on the pancreatic tumor microenvironment will identify new approaches to sensitize pancreatic
cancer to existing therapies including immunotherapy.
The central hypothesis will be tested through three specific aims –
1. Dissect Notch signaling in the pancreatic cancer microenvironment;
2. Define the mechanism and direct effects of Notch signaling on myeloid polarization and function;
2. Target Notch signaling to alleviate immune suppression in pancreatic cancer.
We will use a combination of human and mouse pancreatic cancer samples, genetically engineered mouse
models, orthotopic tumor models, and human and murine tumor cell lines will be used. In addition, we will use
human organoids and cancer associated fibroblasts, together with patient-matched immune cells. Notch
signaling will be disrupted via genetic and pharmacologic approaches both in vivo and in vitro to define its role
in myeloid compartment function. The proposed work is innovative because it defines novel roles of Notch
signaling in pancreatic cancer outside its known epithelial function.
It is significant because it allows for the potential development of new immunomodulatory treatments for this
deadly disease.

## Key facts

- **NIH application ID:** 10464043
- **Project number:** 1R01CA271510-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Filip Bednar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $521,831
- **Award type:** 1
- **Project period:** 2022-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10464043

## Citation

> US National Institutes of Health, RePORTER application 10464043, Dissecting the role of Notch signaling in the pancreatic cancer microenvironment. (1R01CA271510-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10464043. Licensed CC0.

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