# TBEL Project 3

> **NIH NIH U54** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2024 · $286,893

## Abstract

PROJECT 3 - ABSTRACT
Pancreatic cancer arises from non-invasive precursor lesions that are curable if detected and treated early.
Pancreatic intraepithelial neoplasia (PanIN) is the most common of these precursor lesions and represents a
critical target of early detection and cancer prevention approaches. Previous studies from our group have
highlighted critical genomic alterations that drive clonal expansion and neoplastic progression in some PanINs.
These studies have also demonstrated that expansion and progression can occur without the accumulation of
additional driver genomic alterations, suggesting that diverse driver mechanisms operate in different PanINs.
The overall hypothesis of this proposal is that the transition to HG PanIN can be driven by genomic or precursor
microenvironment (PME) alterations, with distinct drivers dominating in different lesions. To investigate this
hypothesis, the proposed studies will evaluate both cell intrinsic and cell extrinsic drivers of neoplastic
progression in human PanIN samples. We will employ a novel approach that allows both three-dimensional
reconstruction and molecular analysis of human PanIN samples. We will perform multi-region whole exome
sequencing and evolutionary reconstruction in order to correlate genomic alterations with expansion and
progression of neoplastic cells in three dimensions. In order to identify non-genetic drivers of neoplastic
progression, we will analyze immune and stromal cell subsets in the same three-dimensionally reconstructed
PanIN samples using imaging mass cytometry, allowing us to determine the variability of key components of the
PME across multiple regions of these PanIN samples. This complementary analysis will allow us to correlate the
microenvironmental features with the molecular alterations in associated PanIN cells. We will also integrate
predicted neoantigens and T-cell receptor sequencing on the same PanIN regions, providing a multi-dimensional
analysis of the immune response to PanINs. Taken together, these approaches will systematically evaluate
potential drivers of progression in the neoplastic cells and associated immune response, providing crucial
biological insights and a rational foundation for novel early detection and prevention approaches.

## Key facts

- **NIH application ID:** 10922846
- **Project number:** 5U54CA274371-03
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Laura DeLong Wood
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $286,893
- **Award type:** 5
- **Project period:** 2022-09-21 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10922846

## Citation

> US National Institutes of Health, RePORTER application 10922846, TBEL Project 3 (5U54CA274371-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10922846. Licensed CC0.

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