# Project 3 ADM

> **NIH NIH U54** · UNIVERSITY OF FLORIDA · 2023 · $116,025

## Abstract

ABSTRACT – FULL PROJECT 3
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most devastating cancers with poor prognosis
and rising incidence. To combat this deadly disease, we should direct our efforts towards preventing PDAC or
halting the progression of precursor lesions to invasive disease parallel to developing novel treatments. One of
the earliest known initiating events for PDAC is the process of acinar-to-ductal metaplasia (ADM).
Understanding and reduction of ADM formation may reduce early PDAC development and progression. Blacks
display a significantly increased incidence and mortality from PDAC compared to other races for unknown
reasons. The role of race on pancreatic ADM and its contributions to the development and progression of
PDAC need to be addressed. In our previous studies, we used normal pancreatic acinar tissues from Black,
White and Hispanic donors to study the impact of race on acinar-to-ductal metaplasia (ADM) and found that
Blacks undergo ADM to a greater extent than Whites or Hispanics. In this competitive renewal, we will expand
on and extend our previous study by including diseased tissues from CP and PDAC from White, Black, and
Hispanic donors since accumulating evidence suggest that chronic pancreatitis (CP) is a major precursor to the
development of PDAC. We will investigate the impact of race on the cellular and molecular events regulating
the interplay between ADM and the microenvironment. Guided by our published and unpublished results, we
hypothesize that the racial disparities seen in PDAC are related to differences in how the pancreas
microenvironment develops during ADM, which means that ADM and its surrounding microenvironment can be
used as a target to treat PDAC. We propose the following specific aims to address this hypothesis: Aim 1: The
impact of race on ADM from the healthy pancreas, CP, and PDAC tissues. Aim 2: The roles of pancreatic
stellate cells and macrophages in ADM and ADM reversal. Aim 3: Contributions of the race to ADM reversal
and cell heterogeneity. The proposed studies will impact the field of pancreatic cancer by providing a missing
link between disparities, ADM, tumor microenvironment, and potential treatments for CP and PDAC. The
specific focus on the racial contributions of microenvironment remolding during pancreatic metaplasia aligns
with the Florida-California Cancer Research, Education and Engagement (CaRE2) Health Equity Center’s
overall goal to eliminate cancer health disparities among Blacks and Latinos in California, Florida, and across
the U.S..

## Key facts

- **NIH application ID:** 10762126
- **Project number:** 2U54CA233444-06
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** THOMAS D. SCHMITTGEN
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $116,025
- **Award type:** 2
- **Project period:** 2018-09-17 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10762126

## Citation

> US National Institutes of Health, RePORTER application 10762126, Project 3 ADM (2U54CA233444-06). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10762126. Licensed CC0.

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