# Calcineurin in pancreatitis

> **NIH NIH R01** · STANFORD UNIVERSITY · 2020 · $400,584

## Abstract

   
DESCRIPTION (provided by applicant):  Pancreatitis is a major life-threatening health problem. An important iatrogenic cause of pancreatitis occurs after a common GI procedure called an endoscopic retrograde cholangiopancreatography (ERCP). Although recent pancreatic duct stenting and anti-inflammatory prophylaxis have improved post-ERCP pancreatitis (PEP) outcomes, PEP is still a formidable problem that is recognized by NIDDK as a disease of interest. Furthermore, the molecular mechanisms underlying PEP remain elusive. Our lab actively examines the role of aberrant Ca2+ signals in the pathogenesis of pancreatitis. In preliminary data, we have identified that the radiocontrast (RC) instilled into the pancreatico-biliary ducts during ERCP triggers robust cytosolic Ca2+ signals in pancreatic acinar cells and induces the activation of the Ca2+ phosphatase calcineurin (Cn). Thus the overall goal of the proposal is to examine the role of Ca2+ and Cn in mediating PEP, with emphasis on RC exposure. Our overarching hypothesis is that a primary mechanism for PEP is the induction of aberrant pancreatic acinar cell Ca2+ signals and activation of Cn. Our specific aims are (Aim 1) to examine how RC exposure to the pancreas (1a) induces aberrant acinar cell Ca2+ signals and (1b) activates Cn; (Aim 2) to examine whether Cn activation by RC is critical to inducing (2a) NF- κB inflammatory signals and (2b) pancreatic injury; and (Aim 3) to determine (3a) whether acinar cells are a critical site of Cn activation during PEP and (3b) whether targeted delivery of Cn inhibitors to the pancreas will prevent PEP. We believe that the proposal will provide a solid basis to examine the role of Ca2+ and Cn pathways in mediating PEP and pancreatitis, with the anticipated goal to devise targeted therapies for preventing PEP and potentially treating pancreatitis with Cn inhibitors.

## Key facts

- **NIH application ID:** 10004607
- **Project number:** 5R01DK093491-10
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Sohail Z Husain
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $400,584
- **Award type:** 5
- **Project period:** 2019-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10004607

## Citation

> US National Institutes of Health, RePORTER application 10004607, Calcineurin in pancreatitis (5R01DK093491-10). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10004607. Licensed CC0.

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