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

> **NIH NIH R01** · STANFORD UNIVERSITY · 2022 · $683,859

## Abstract

PROJECT SUMMARY
Tyrosine kinase inhibitors (TKIs) have been shown to significantly decrease a variety of malignancy-related
mortality in the past two decades. However, concerns have been raised due to their potential vascular toxicity
that could lead to hypertension, myocardial infarction, stroke, and peripheral arterial diseases. Despite these
safety concerns, the mechanisms underlying TKI-induced vascular toxicity (TKI-VT) are poorly understood. To
overcome this challenge, we propose to leverage human iPSCs, state-of-the-art multi-omics methods, and
CRISPR screening to investigate molecular and cellular mechanisms of TKI-VT and identify druggable targets
that can be further tested in animal models. Specifically, in Aim 1, we will comprehensively profile human-induced
pluripotent stem cell-derived cardiac pericytes (iPSC-PCs), an important but rarely explored cardiac cell type, to
define cellular mechanisms of TKI-VT. In Aim 2, we will evaluate how TKIs induce disrupted cellular crosstalk
between iPSC-PCs and iPSC-derived endothelial cells (iPSC-ECs) by performing integrative omics on a 3D
vessel-on-chip (VoC) model. Finally, in Aim 3, we will perform CRISPR screening on TKI-treated iPSC-PCs and
iPSC-ECs to identify potential druggable targets and validate their therapeutic efficacy in mice. Successful
completion of these studies will lead to novel mechanistic insights into TKI-VT pathogenesis and help develop
promising therapeutic strategies that can prevent and/or treat TKI-VT in cancer patients. Moreover, this proposal
will help define the role of TKIs in vascular pathophysiology, which may have broad scientific and clinical
implications beyond cardio-oncology.

## Key facts

- **NIH application ID:** 10518663
- **Project number:** 2R01HL141851-05
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Lei Stanley Qi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $683,859
- **Award type:** 2
- **Project period:** 2018-08-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10518663

## Citation

> US National Institutes of Health, RePORTER application 10518663, Modeling Tyrosine Kinase Inhibitor-Induced Vascular Dysfunction Using Human iPSCs (2R01HL141851-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10518663. Licensed CC0.

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