# Interrogation of the Impact of Selection on the Evolution of Human Pancreatic Cancer Precursor Lesions

> **NIH NIH U01** · JOHNS HOPKINS UNIVERSITY · 2024 · $515,949

## Abstract

Project Summary
Pancreatic cancer arises from precancerous lesions that are curable if detected and treated early enough.
Recent multi-region genomic analyses of one type of precancerous pancreatic lesion, intraductal papillary
mucinous neoplasm (IPMN), suggest unique evolutionary and selective pressures in IPMNs compared to
invasive cancers, underscoring the potential importance of selection in the progression of precancerous
lesions. We propose to characterize the role of selective forces in IPMNs using comprehensive molecular
analyses and computational data integration of both human IPMN tissue samples and organoid cultures. We
will determine the molecular features of progressed subclones in human IPMN samples using multi-region
whole genome sequencing and RNA-sequencing. In addition, we will develop and apply novel multi-omics
computational methods to integrate DNA and RNA-sequencing data to delineate selective forces in human
IPMNs. We will determine the function of progressed clones identified by whole genome DNA sequencing with
gene signatures inferred from bulk transcriptional data in a new semi-supervised framework. We will then
employ a three-dimensional in vitro organoid culture model of human IPMN cells to characterize the relative
contributions of selective pressures over time. We will use combined DNA sequencing and single-cell RNA-
sequencing to identify gene expression signatures of progressed subclones in our organoid model, further
adapting our computational framework to single cell RNA-sequencing data. Taken together, the proposed
studies combine direct analysis of human tissue samples and manipulation of human precancerous cells in
three-dimensional culture with novel multi-omics computational integration to greatly expand our knowledge of
the role of selection in pancreatic cancer precursor lesions.

## Key facts

- **NIH application ID:** 10911181
- **Project number:** 5U01CA271273-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Elana Fertig
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $515,949
- **Award type:** 5
- **Project period:** 2022-09-15 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10911181

## Citation

> US National Institutes of Health, RePORTER application 10911181, Interrogation of the Impact of Selection on the Evolution of Human Pancreatic Cancer Precursor Lesions (5U01CA271273-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10911181. Licensed CC0.

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