# Mechanisms of Hereditary Pancreatitis

> **NIH NIH R01** · MAYO CLINIC  JACKSONVILLE · 2020 · $352,125

## Abstract

Abstract:
 Hereditary pancreatitis (HP) is an autosomal-dominant disorder with recurrent episodes of acute
pancreatitis (AP) that eventually develops into chronic pancreatitis (CP). Cationic trypsinogen gene (or
PRSS1) mutations are the most common causes of HP. Importantly, HP patients have an extremely high
risk of developing pancreatic cancer than other forms of CP. Unfortunately, the development of targeted
preventive or therapeutic interventions for HP has been hampered by gaps in our understanding of its
pathophysiology, which is mainly due to the practical difficulties in obtaining tissues from the pancreas
during the early stages of the disease and the lack of animal models that recapitulate the human form of
the disease. Recently we have developed a novel model of HP by expressing a common mutant of
human PRSS1 (PRSS1R122H) in mice at a level equivalent to that found in human HP. This new model
will provide us with a powerful tool to fulfill our long-term goal of understanding the initiating events of
HP and developing specific strategies for its prevention and therapy. In this proposal, we will use our
unique humanized pancreatitis model to test our central hypothesis that etiological factors interact with
genetic changes to increase trypsin activity, which causes pancreatitis by cell-autonomous cell death
signaling pathways and non-cell-autonomous inflammatory pathways. We will characterize these
signaling pathways in the HP model and investigate their roles by both pharmacological and genetic
approaches. We expect these studies will significantly improve our understanding of the specific role of
intracellular human trypsinogen activation during the pathogenesis of HP and provide new insights for
preventive and therapeutic interventions. Importantly, our novel clinically relevant model will provide a
powerful tool for developing and testing such interventions.

## Key facts

- **NIH application ID:** 9976505
- **Project number:** 5R01DK117910-02
- **Recipient organization:** MAYO CLINIC  JACKSONVILLE
- **Principal Investigator:** Baoan Ji
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $352,125
- **Award type:** 5
- **Project period:** 2019-07-12 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9976505

## Citation

> US National Institutes of Health, RePORTER application 9976505, Mechanisms of Hereditary Pancreatitis (5R01DK117910-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9976505. Licensed CC0.

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