# Defining the role of chromatin remodeling complexes in pancreatic cancer stem cells

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $39,805

## Abstract

Project Summary
Pancreatic adenocarcinoma (PDAC) is a devastating disease characterized by high rates of metastasis and
poor therapeutic response. It is currently the 4th leading cause of cancer related deaths in developed countries
and despite efforts to improve therapy, the five-year survival rate remains at 9%. Therefore it is critical to
identify new programs that drive pancreatic cancer progression and therapeutic resistance. To define new
cancer dependencies, work in the Reya lab has focused on characterizing stem cell programs that drive cancer
initiation, propagation, and relapse. Previously published studies have demonstrated that the fate determinant
Musashi2 functionally marks a stem population in pancreatic cancer, and more recent work has revealed that
this stem cell population is characterized by a highly unique transcriptional and epigenetic profile. Given the
crucial role for epigenetic regulation in development and dysregulation in cancer, it is logical to hypothesize
that differentially expressed epigenetic regulatory factors could be responsible for the establishment or
maintenance of this unique stem cell state in pancreatic cancer. Using functional screens to profile the impact
of inhibition of candidate epigenetic factors on stem cells in vitro, the gene Smarcd3 has been identified as a
potential critical mediator of stem cell growth in pancreatic cancer. Smarcd3 encodes Baf60c, a component of
the SWI/SNF nucleosome remodeling complex that is known to be dysregulated in pancreatic cancer.
Preliminary studies have shown that Smarcd3 inhibition leads to reduced growth of KPf/fC pancreatic cancer
stem cells in vitro and in vivo. Smarcd3 inhibition also leads to reduced anchorage-independent growth of
human pancreatic cancer cell lines in vitro. Based on these data, the aims of this proposal are to test the
hypotheses that (1) Smarcd3 is required for pancreatic cancer growth and stem cell expansion in genetically
engineered mouse models, and (2) Smarcd3 is required for growth of human pancreatic cancer cell lines and
patient-derived pancreatic cancer xenografts.

## Key facts

- **NIH application ID:** 10090454
- **Project number:** 5F31CA247489-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Lesley Paige Ferguson
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $39,805
- **Award type:** 5
- **Project period:** 2020-01-06 → 2022-01-05

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10090454

## Citation

> US National Institutes of Health, RePORTER application 10090454, Defining the role of chromatin remodeling complexes in pancreatic cancer stem cells (5F31CA247489-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10090454. Licensed CC0.

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