# Modeling Tyrosine Kinase Inhibitor-Induced Vascular Dysfunction Using Human iPSCs

> **NIH NIH R01** · STANFORD UNIVERSITY · 2021 · $562,562

## Abstract

PROJECT SUMMARY
The development of small molecule tyrosine kinase inhibitors (TKIs) has led to a dramatic increase in life
expectancy for patients suffering from cancers such as leukemias, carcinomas, and melanomas. TKIs inhibit
the kinase phosphorylation activity of hyperactive receptor tyrosine kinases (RTK), thereby stymying the
enhanced cell survival, proliferation, and migration phenotypes that are hallmarks of cancer progression.
However, some TKIs are linked to severe vascular side effects such as endothelial toxicity and hypertension.
Therefore, methods for accurately assessing TKI-induced vascular toxicity (TKI-VT) must be established. In
vitro modeling of vascular toxicity and cardiovascular disease is of interest as human adult vascular
endothelial cells are difficult to isolate and propagate long-term in culture, and animal models have often
proven non-predictive of the drug response in patients. Patient-specific human induced pluripotent stem cell-
derived endothelial cells (iPSC-ECs) represent a novel technology for modeling cardiovascular diseases.
Human iPSC-ECs have already been successfully applied to understanding basic mechanisms of pulmonary
hypertension and obesity-induced endothelial dysfunction. Human iPSC-ECs have also been used to screen
for efficacy and toxicity of various cardiovascular drugs. Indeed, our preliminary data shows endothelial
dysfunction in patient-specific iPSC-ECs when treated with TKIs. Here, in our multi-PI resubmission, we
hypothesize that human iPSC-ECs represent a novel platform for studying the mechanisms and validity of
genomic hits in regulating TKI-VT.

## Key facts

- **NIH application ID:** 10191012
- **Project number:** 5R01HL141851-04
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** THOMAS QUERTERMOUS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $562,562
- **Award type:** 5
- **Project period:** 2018-08-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10191012

## Citation

> US National Institutes of Health, RePORTER application 10191012, Modeling Tyrosine Kinase Inhibitor-Induced Vascular Dysfunction Using Human iPSCs (5R01HL141851-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10191012. Licensed CC0.

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