# Interrogation of the Impact of Selection on the Evolution of Human PancreaticCancer Precursor Lesions

> **NIH NIH U01** · JOHNS HOPKINS UNIVERSITY · 2024 · $163,750

## Abstract

Project Summary
This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA-
24-029.
Intraductal papillary mucinous neoplasms (IPMN) are premalignant lesions that can develop into invasive
pancreatic ductal adenocarcinoma (PDAC). Most pancreatic premalignancies are microscopic and not
identifiable by current imaging exams. The only PDAC precursor that can be diagnosed by imaging test are the
IPMNs. Since not all IPMN develop into PDAC, it is critical to understand the evolution of this premalignant
lesions to develop diagnostic tools to discriminate the ones that require therapeutic intervention to prevent
cancer. The Parent U01 award proposes a systems biology approach, combining DNA-sequencing, RNA-
sequencing and refined computational tools, to characterize the clonal evolution of IPMN by examining clinical
specimens and patient derived organoid models. Although DNA- and RNA-sequencing have demonstrated
power to study the evolutionary trajectory and functional impact of molecular perturbations, respectively, the bulk
profiling does not allow proper interpretation of the TME composition and the cellular interactions happening
within the premalignant microenvironment. Therefore, we propose a new collaboration with Dr. Luciane
Kagohara to include on our systems biology approach the spatial transcriptomics analysis of human IPMN
samples to examine within the tissue context the transcriptional state of the premalignant microenvironment (Aim
1) and understand the intercellular interactions that are associated with the clonal evolution of these PDAC
precursors (Aim 2). This project enables further experimental and computational techniques to broaden the
comprehensive investigation of PDAC progression that could identify potential signatures for early detection and
therapy.

## Key facts

- **NIH application ID:** 11070533
- **Project number:** 3U01CA271273-03S1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Elana Fertig
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $163,750
- **Award type:** 3
- **Project period:** 2022-09-15 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11070533

## Citation

> US National Institutes of Health, RePORTER application 11070533, Interrogation of the Impact of Selection on the Evolution of Human PancreaticCancer Precursor Lesions (3U01CA271273-03S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11070533. Licensed CC0.

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