# Metaplastic Tuft Cells in Pancreatic Cancer

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $477,977

## Abstract

Abstract
Pancreatic ductal adenocarcinoma (PDA) is the 3rd most common cause of cancer-related
death in the United States. This dismal outcome is in part due to the lack of understanding of
the unique pathology of PDA that includes pronounced epithelial plasticity and evolution of an
extensive reactive fibroinflammatory stroma. We have discovered an unusual cell type within
preneoplasia and neoplasia known as the metaplastic tuft cell (MTC), which has been proposed
to act as both a tumor initiating cell and as a chemosensory cell that drives the
fibroinflammatory host response. Normal tuft cells are found in normal glandular tissues and are
marked by the expression of the microtubule kinase DCLK1. There they sample the luminal
environment and respond to signals by modifying the Type 2 immune response. While there are
no tuft cells found in the normal pancreas, they arise in a transdifferentiation event to become
part of the metaplastic and neoplastic epithelium during oncogenesis or tissue injury. Besides
their chemosensory function, they have been hypothesized to be a tumor initiating progenitor
cell. In order to definitively determine the origins and functions of the metaplastic tuft cell, we
have created a dual recombinase driven mouse model of pancreatic neoplasia combined with
an inducible Cre recombinase that specifically targets MTCs that will allow us to alternatively
trace and target the metaplastic tuft cells independent of neoplastic transformation in vivo. We
have also devised human and mouse organoid culture systems that preserve tuft cell
differentiation, so that we can study their genesis, fate and chemosensory function in more
detail. Together, these tools will be used to rigorously determine the function of the metaplastic
tuft cell and whether manipulating their functions can be used to treat pancreatic cancer.

## Key facts

- **NIH application ID:** 9997360
- **Project number:** 1R01CA247516-01A1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Howard C. Crawford
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $477,977
- **Award type:** 1
- **Project period:** 2020-03-09 → 2020-12-04

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9997360

## Citation

> US National Institutes of Health, RePORTER application 9997360, Metaplastic Tuft Cells in Pancreatic Cancer (1R01CA247516-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9997360. Licensed CC0.

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