# Investigating the relationship between macrophage ontogeny and function during pancreatitis

> **NIH NIH F31** · WASHINGTON UNIVERSITY · 2021 · $31,962

## Abstract

Project Summary/Abstract
Inflammation associated with pancreatitis initiates accumulation of leukocytes within the pancreas. Chief
among these cells are macrophages, neutrophils, and T cells. Although studies have identified important roles
for each of these cell types in pancreatitis, most of the focus has been on macrophages, as they are thought to
be potent drivers of inflammatory cytokine production. Despite this, targeting macrophage-produced cytokines
has not seen much success therapeutically. This, along with the fact that pancreatitis is a well described risk
factor for pancreatic cancer, illustrates the need for establishing better ways to target the cell types driving
disease progression. Although macrophages are an attractive therapeutic target in both pancreatitis and
pancreatic cancer, study thus far has primarily focused on those derived from infiltrating monocytes. Recent
lineage-tracing studies have shown that macrophages within tissues originate not only from monocytes, but
also from embryonic progenitors during fetal development. Further, it has been shown that in some models of
pathogenesis, including pancreatic cancer, embryonic-derived macrophages adopt unique functions from those
derived from monocytes. Study of pancreatic cancer also revealed that embryonic macrophages may uniquely
promote tumor progression and changes in fibrosis. However, it is not fully understood what mechanisms drive
macrophages of different origin to react differently, and how embryonic-derived macrophages might impact
tumor progression differently than those derived from monocytes. I hypothesize that macrophages of different
origin adopt functionally distinct roles in both pancreatitis and pancreatitis-associated pre-malignant
progression. Preliminarily, I have shown that both embryonic and monocyte-derived macrophages accumulate
in the pancreas during pancreatitis. Additional lineage-tracing mouse models will be used here to strengthen
this argument and allow me to investigate changes in activation of these populations between steady-state and
inflammation. Reducing monocyte-derived macrophages by genetic deletion of the CCR2 gene, involved in
monocyte trafficking, is not sufficient to restrain total macrophage numbers in the pancreas during pancreatitis,
and these mice show no difference in disease progression. Targeting the embryonic macrophage subset may
further help us understand the functional role of these cells and determine their therapeutic efficacy. These
aims will not only help expand our knowledge of macrophage biology, but also focus on my long-standing
interests in immunology and human disease. The training received through this proposal will also build upon
my technical skills in immunology and study of cancer biology. These invaluable skills will allow me to further
push towards my career goals of improving cancer immunotherapies and impact of immune modulation on
inflammatory disorders.

## Key facts

- **NIH application ID:** 10116955
- **Project number:** 5F31DK122633-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** John M Baer
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $31,962
- **Award type:** 5
- **Project period:** 2020-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10116955

## Citation

> US National Institutes of Health, RePORTER application 10116955, Investigating the relationship between macrophage ontogeny and function during pancreatitis (5F31DK122633-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10116955. Licensed CC0.

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