# Center for Enteric Diseases in Engineered Tissues

> **NIH NIH U19** · TUFTS UNIVERSITY BOSTON · 2020 · $21,880

## Abstract

Enteric infectious diseases are important causes of morbidity and mortality worldwide, with diarrheal diseases
being among the leading causes of death in the young. Detailed understanding of the interaction between
enteropathogens and the human host is limited due to the inaccessibility of pathogens while growing within
host tissues. Workers generally reconstruct human disease events using animal infection and tissue culture-
based models to analyze the pathogen-host interface. Human diseases, however, are often poorly reproduced
in animal models, while tissue culture models lack the complexity to fully reconstruct events during disease that
bring in a complex group of host cells. To address these issues and provide more physiologically relevant
models for use by workers studying enteropathogenesis, this application proposes a Center on Enteric
Diseases in Engineered Tissues (CEDET) to generate bioengineered three-dimensional models of human
tissue derived from human clinical intestinal cells. The engineered tissues developed by the CEDET team will
be challenged directly with enteropathogens in a quest to develop analytic strategies that more accurately
mimic events that occur in the human host compared to work in known tissue culture models.
The CEDET brings investigators from the Engineering and Medical campuses of Tufts University together with
a gastroenterologist to focus on identifying new strategies for analyzing the interface between enteropathogens
and intestinal cells of clinical origin. The proposed CEDET will develop engineered tissue platforms for
pathogens having specific metabolic requirements, described as individual but synergizing projects. In Project
1, the engineered tissues will be used to generate a model system in which the apical and basal faces of the
epithelium will be exposed to different O2 tensions, to allow the study of Clostridium difficile, a strict anaerobic
organism. Project 2 will develop a 3D in vitro tissue model of the human intestine tunica mucosa and study
infections of human epithelium by Vibrio cholera and enteropathogenic Yersinia spp. This Project will allow the
development of a tractable 3D human intestinal tissue model system for studying the specific mechanistic
steps that are important for enteric pathogens to successfully colonize the host intestine. Finally, in Project 3,
the 3D intestinal models will be used to overcome the technical hurdle of developing a system for continuous
propagation of Cryptococcus, investigation of host-parasite interactions in primary human cells and a system
for drug screening recapitulating human gut structure. Each of the Projects is driven by Aims that propose to
construct artificial tissues of increasing complexity, bringing in immune cells, primary cells derived from
endoscopic isolation in the clinic, and human microbiome samples in O2-controlled environments. The entire
Center will be driven by Administrative and Scientific Cores, which have the express purpose o...

## Key facts

- **NIH application ID:** 10071561
- **Project number:** 3U19AI131126-03S1
- **Recipient organization:** TUFTS UNIVERSITY BOSTON
- **Principal Investigator:** Ralph R. Isberg
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $21,880
- **Award type:** 3
- **Project period:** 2017-04-07 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10071561

## Citation

> US National Institutes of Health, RePORTER application 10071561, Center for Enteric Diseases in Engineered Tissues (3U19AI131126-03S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10071561. Licensed CC0.

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