# Unraveling the Role of p53 in Endothelium Homeostasis after Ionizing Radiation Exposure

> **NIH NIH K99** · STANFORD UNIVERSITY · 2024 · $149,948

## Abstract

Project summary
Radiation therapy is an important component of cancer treatments, yet its usage has been hampered due to side
effects to normal tissue. The current K99/R00 project seeks to investigate the molecular landscape of radiation
induced coronary heart disease (RICHD), a leading cause of morbidity and mortality among cancer survivors.
The complex nature of RICHD necessitates a comprehensive understanding of patient-specific risk factors and
underlying genetic variations. Focusing on the pivotal role of endothelial to mesenchymal transition (EndMT) and
its correlation with variations in p53 signaling due to TP53 mutations, I will utilize human-induced pluripotent
stem cells (iPSCs) from cancer patients with TP53 mutations and transgenic mouse models in the mentored K99
phase. In my first aim, I will utilize 3D vessel-on-a-chip model (VoC) lined with iPSC-derived endothelial cells
and smooth muscle cells from cancer patients with or without TP53 mutations for longitudinal endothelial lineage
tracing analysis with vascular functional assays after exposure to 2 Gy of X-rays radiation. In my second aim, I
will generate a novel endothelial lineage tracing mouse model with TP53 mutations and elucidate the functional
and molecular alterations after exposure to 20 Gy of X-rays radiation on the heart. Both projects employ in-depth
single cell RNA-sequencing (scRNA-seq) analysis to map the gene regulatory networks perturbations across
different cell-types at varied time points post-irradiation. This project will be guided by an advisory committee
constituted of researchers bringing their distinct expertise: Joseph Wu (Precision Medicine), Laura Attardi (TP53
Biology), Sharon Gerecht (Vascular Engineering), Billy Loo (Radiation Oncology), Kristy Red-Horse (Lineage
Tracing), Michael Snyder (Integrative Omics Analysis). The training received under this mentorship will equip me
with invaluable expertise in tissue engineering, lineage tracing and scRNA-seq analysis. Ultimately, this will foster
my transition to the independent phase (R00), where I aim to establish genotype-phenotype correlations for
RICHD in iPSC-derivatives. Functional radiogenomics on vascular cells will provide novel insights and a
roadmap for stratifying TP53 mutations in RICHD offering a significant advancement for cancer patients
undergoing radiation therapy.

## Key facts

- **NIH application ID:** 10866250
- **Project number:** 1K99HL173685-01
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Won Suk Jahng
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $149,948
- **Award type:** 1
- **Project period:** 2024-08-09 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10866250

## Citation

> US National Institutes of Health, RePORTER application 10866250, Unraveling the Role of p53 in Endothelium Homeostasis after Ionizing Radiation Exposure (1K99HL173685-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10866250. Licensed CC0.

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