# High-throughput nanoIEA-based Assay for Screening Immune Cell-Vascular Interactions

> **NIH NIH R21** · CORNELL UNIVERSITY · 2024 · $237,913

## Abstract

PROJECT SUMMARY
Blood vessels play a central role in maintaining host immunity by transporting immune cells to sites of infection.
During the process, blood vessels experience endothelial junction remodeling to control vascular permeability
and immune cell extravasation. Under infection, blood vessels become permeable and allow immune cells to
extravasate and kill pathogens in the interstitium. Once the infection is resolved, permeable vessels become less
permeable and limit the number of interstitial immune cells. However, sometimes in inflammation, the remodeling
is perturbed, resulting in prolonged, hyper-permeable blood vessels. This vascular dysfunction contributes to
immune diseases, such as chronic inflammation, lupus, and autoimmune disease. It is known that endothelial
cell alignment is crucial to maintain intact cell-cell adhesion and promote junction maturation. Despite the
significance of the cell alignment in functional endothelium, currently available high-throughput methods, such
as real-time cell analysis (RTCA) and trans-epithelial/trans-endothelial electrical resistance (TEER) systems with
randomly seeded cells have not successfully measured cell impedance or electrical resistance through the in
vivo-like controlled endothelial cell morphology, alignment, and matured cell-cell junctions. Furthermore, the
current technologies lack pericyte co-culture with endothelial cells. In this proposal, we will develop a high-
throughput, high-content functional screening assay capable of faster drug screening and mechanistic studies
on blood vessel barrier function and immune cell extravasation. To achieve our goals, we will establish a
nanopatterned IEA-based functional assay for high-throughput phenotype screening of pericyte-covered
endothelium. To establish the nanopatterned IEA-based assay, we will determine conditions for junctional
maturation of human dermal and lung microvascular endothelial cells with or without pericytes, focusing on (i)
degree of cell alignment; (ii) expression of adherens junctions, polarization, and basement membrane markers;
(iii) vascular barrier function (Aim 1.1). We will then assess vascular gene expression profiles related to vessel
stabilization and immune cell adhesion. We will next evaluate immune cell extravasation through the endothelium
in the non-inflammatory condition to determine immune cell behaviors in steady-state blood vessels (Aim 1.2).
Next, we will validate the utility of the system for inflammation-induced blood vessel dysfunction. To achieve this
aim, we will examine the endothelial barrier function and immune cell extravasation in five different categories of
inflammatory cytokines and various levels of substrate stiffness considering skin and lung microenvironments
(Aim 2.1). Lastly, we will identify potential targets and drugs to reverse vessel dysfunction by focusing on
abrogation of the cytokine effect and the stiffness effect, separately or in combination (Aim 2.2). In summary, our...

## Key facts

- **NIH application ID:** 10830332
- **Project number:** 5R21AI168886-02
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Deok-Ho Kim
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $237,913
- **Award type:** 5
- **Project period:** 2023-04-19 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10830332

## Citation

> US National Institutes of Health, RePORTER application 10830332, High-throughput nanoIEA-based Assay for Screening Immune Cell-Vascular Interactions (5R21AI168886-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10830332. Licensed CC0.

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