# Clinical Trials in a Dish Using a Personalized Multi-Tissue Platform for Atopic Dermatitis

> **NIH NIH UG3** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $599,999

## Abstract

ABSTRACT
Drug development is an inefficient and expensive process, in which a drug can fail late in
phase 3 clinical trials or due to the unanticipated manifestation of severe side-effects after
release onto the market. For example, Dupilumab, an Interleukin-4 receptor antagonist for
 ,
atopic dermatitis (AD), often causes adverse reactions such as keratitis, eye pruritus and
dry eyes and nasopharyngitis. AD is one of the most common chronic inflammatory skin
diseases, affecting 15-20% of children and 1-3% of adults worldwide. AD is a complex
and multifactorial disease, and AD pathogenesis is driven by genetic factors, as well as
by environmental cues. The filaggrin (FLG) gene is believed to play a crucial role in the
pathophysiology of AD. Moreover, there is a link between AD lesions and Staphylococcus
Aureus (S. Aureus) colonization, since it is observed that ~90% of AD patients are
colonized with S. aureus in lesional skin, and increased S. Aureus loads correlate with
disease flares in the affected skin. Animal models have been developed to delineate AD
pathogenesis and for preclinical drug testing, however, these models fall short of faithfully
recapitulating the pleiotropic disease phenotypes since mice do not spontaneously
develop AD. Likewise,
in vitro models of AD do not recapitulate
the crosstalk between
different organs involved in AD. In this project, we will establish a functional network of
three tissue systems comprised of skin, cornea and nasal tissues, as well as circulating
T cells and microbiota (Sk-Co-Na-T-MB) to model AD. This platform will enable a multi-
factorial approach to delineating AD pathogenesis, as well as provide unprecedented
predictive power to detect drug toxicity/efficacy in a genetically-defined cohort of AD
patients iPSCs. We will validate the platform by examining the efficacy/toxicity of several
FDA-approved and emerging AD drugs, including Dupilumab (an Interleukin-4 receptor
antagonist), Apremilast (a PDE4 inhibitor) and Tofacitinib (a pan-JAK inhibitor). Finally,
we will also investigate the compounding effects of genetic and environmental risk factors
(microbiota and FLG mutations), and our AD patient cohort will reflect the gender and
ethnic diversity of patient populations receiving AD drugs, allowing us to perform clinically-
relevant and patient-specific Clinical Trials in a Dish for Atopic Dermatitis.

## Key facts

- **NIH application ID:** 10038233
- **Project number:** 1UG3AR079297-01
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Angela M Christiano
- **Activity code:** UG3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $599,999
- **Award type:** 1
- **Project period:** 2020-09-23 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10038233

## Citation

> US National Institutes of Health, RePORTER application 10038233, Clinical Trials in a Dish Using a Personalized Multi-Tissue Platform for Atopic Dermatitis (1UG3AR079297-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10038233. Licensed CC0.

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