# Developmental toxicants and congenital pancreas malformations

> **NIH NIH R21** · UNIVERSITY OF MASSACHUSETTS AMHERST · 2022 · $230,340

## Abstract

Project Summary
 Early life stage exposures to xenobiotics can result in aberrant pancreatic development, which may
predispose an individual to pancreatitis and metabolic dysfunction. A common mode of toxicity shared by
numerous compounds is the generation of reactive oxygen species (ROS) and redox stress. ROS and cellular
redox potential play fundamental roles in normal embryonic development and cell signaling. Perturbation of
these processes resulting from xenobiotic exposure can alter cell fate decisions, resulting in functional or
structural alterations that only become apparent with subsequent stress or age. However, surprisingly little is
known about how embryos respond to redox stress, or the impact of xenobiotic exposures on pancreas
development.
 Congenital pancreas malformations in humans are estimated to occur in approximately ten percent of the
population and are associated with obesity, pancreatitis, Type 1 and Type 2 diabetes mellitus. The causes of
these malformations are not well understood, and cannot be fully explained by genetic polymorphisms,
suggesting a strong exogenous component. We have found that early life exposures to PFAS compounds and
pro-oxidants results in a short exocrine pancreas. This grant takes a systems-level approach in transgenic
zebrafish (Danio rerio) embryos to investigate a potential mechanism of oxidative stress in this deformity, and
seeks to establish the functional outcomes of the truncated exocrine pancreas phenotype. Zebrafish are a well-
established, widely used, and powerful model organism for studying vertebrate embryonic development in vivo.
This work will facilitate advancement of a mechanistic understanding of how early-life xenobiotic exposures
and redox stress can damage the developing pancreas and predispose humans to metabolic diseases.

## Key facts

- **NIH application ID:** 10465237
- **Project number:** 5R21ES033532-02
- **Recipient organization:** UNIVERSITY OF MASSACHUSETTS AMHERST
- **Principal Investigator:** Alicia R Timme-Laragy
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $230,340
- **Award type:** 5
- **Project period:** 2021-08-10 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10465237

## Citation

> US National Institutes of Health, RePORTER application 10465237, Developmental toxicants and congenital pancreas malformations (5R21ES033532-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10465237. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*