# Intestinal Stem Cell Responses to Cryptosporidium Infection

> **NIH NIH R21** · CREIGHTON UNIVERSITY · 2020 · $218,250

## Abstract

Summary
Cryptosporidium remains an important opportunistic pathogen in AIDS patients who do not have access to
HAART treatment. This parasite infects the gastrointestinal epithelium in humans; infection in AIDS patients
often leads to life-threatening illness. Cryptosporidium is also a common cause of diarrhea in young children in
developing countries. Indeed, infection with Cryptosporidium shows significant association with mortality in
young children and appears to predispose children to enteric infection with lasting deficits in age-appropriate
body growth and cognitive development. The underlying molecular mechanisms are unclear. The primary
infection site of Cryptosporidium in human is the small intestine, one of tissues in the body that regenerates the
most quickly. In our preliminary study, we observed that Cryptosporidium infection is limited to the villi (mainly
enterocytes) of intestinal epithelium. Nevertheless, infection causes a significant decrease in intestinal stem
cell (ISC) numbers (as well as the expression levels of several ISC markers). We also identified a panel of
genes whose expression levels are significantly altered in enterocytes following infection. Some of these genes
code important components of the signaling pathways in the enterocyte-ISC network and thus, may be
involved in Cryptosporidium-induced ISC dysfunction. Therefore, we hypothesize that Cryptosporidium
infection in the villi of intestinal epithelium impedes ISC function in the crypts through changes of signaling
pathways in the enterocyte-to-ISC network. We will use in vitro, ex vivo, and in vivo infection models and
complementary biochemical, molecular, and morphologic approaches to characterize the dysfunction of ISC
populations (ISC plasticity) during Cryptosporidium infection (Aim 1) and identify the signaling pathways
pertinent to ISC dysfunction induced by infection (Aim 2). With the completion of these aims, we will have
determined the ISC plasticity during Cryprosporidium infection and identified which signaling pathways are
specifically affected by infection leading to ISC dysfunction. These outcomes will establish a foundation on
which to build long-term, mechnistic studies to define the pathogenesis (particularly the long-lasting effects) of
Cryptosporidium infection in the intestine.

## Key facts

- **NIH application ID:** 9931993
- **Project number:** 1R21AI141325-01A1
- **Recipient organization:** CREIGHTON UNIVERSITY
- **Principal Investigator:** Xian-Ming Chen
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $218,250
- **Award type:** 1
- **Project period:** 2020-01-29 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9931993

## Citation

> US National Institutes of Health, RePORTER application 9931993, Intestinal Stem Cell Responses to Cryptosporidium Infection (1R21AI141325-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9931993. Licensed CC0.

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