# Drug Screening with a Biofrabricated 3-D Immunocompetent Skin Model for Drug Discovery in Psoriatic Disease

> **NIH NIH U18** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $641,186

## Abstract

Project Summary
Psoriasis affects 2-3% of the US population. Currently, there are no high throughput screening
methodologies to develop new psoriasis drugs. To meet this significant unmet pharmaceutical
need, we will screen for drugs to treat this disease by using a 3D skin system established with
3D bioprinting, induced pluripotent stem cell (iPSC) reprograming and CRISPR genome-editing
technologies. We successfully constructed 3D skin using exclusively iPSC-derived fibroblasts
iFBs) and keratinocytes (iKCs), demonstrating the feasibility of this approach. 3D bioprinting can
allow us to reproducibly construct complex structures to recapitulate human tissues/organs, and
miniaturize the 3D fabricated skin for high throughput screening. Psoriasis is an inflammatory
skin disorder with abnormal epidermal hyperproliferation, compromised barrier function,
upregulated keratin 16 (KRT16), downregulated filaggrin (FLG) and excessive secretion of
cytokines such as IL-8, which can be monitored with transepithelial/transendothelial electrical
resistance (TEER), fluorescence reporters and IL-8 ELISA as readouts. We postulate that
compounds will manifest their anti-psoriatic effects through the reduction in disease phenotypes
that can be detected by relevant readouts. Psoriasis can be recapitulated and assessed using
cytokine treatment on skin constructs derived from primary fibroblasts (FBs) and keratinocytes
(KCs), however it is labor intensive and inefficient to produce large quantity of T cells and
reporter-containing iPSC-derived keratinocytes (iKCs), Therefore, in this project, we will use
cytokine treatment and skin constructs fabricated with primary cells for initial screening and then
use iPSC-derived 3D skin containing T cells and reporters for subsequent compound validation,
confirmation and the mechanism of actions (MOA) studies. Specifically, we will use FBs and
KCs to bioprint 3D skin in a 96 well format, and treat with a cytokine cocktail containing TNF-a,
IL-1a, IL6 and IL17A, for a pilot screen of 50 inflammation-related compounds to optimize the
high throughput procedure that then will be applied to screen a library of 1000 compounds using
TEER and IL-8 ELISA. Subsequently, we will validate the lead compounds using lactate
dehydrogenase (LDH) toxicity assays and iPSC-derived skin constructs that are generated from
healthy donor cells and containing GFP reporters for KRT16 and mCherry for FLG. Finally,
bioprinted psoriasis-specific iPSC derived skin constructs containing reporters and Th17/Th1
cells will be used to confirm the lead hits and delineate the MOA of compounds using RNA-seq.
Completion of this project will provide us with compounds that may be developed into drugs to
treat psoriasis. Moreover, our 3D skin model-based high throughput system can be easily
adapted to screen for drugs to treat other inflammatory skin diseases.

## Key facts

- **NIH application ID:** 10249327
- **Project number:** 5U18TR003211-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Angela M Christiano
- **Activity code:** U18 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $641,186
- **Award type:** 5
- **Project period:** 2020-08-28 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10249327

## Citation

> US National Institutes of Health, RePORTER application 10249327, Drug Screening with a Biofrabricated 3-D Immunocompetent Skin Model for Drug Discovery in Psoriatic Disease (5U18TR003211-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10249327. Licensed CC0.

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