# Delineating the Genetic Susceptibility of Smoking-Induced Vascular Dysfunction

> **NIH NIH R00** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2024 · $249,000

## Abstract

PROJECT SUMMARY
This proposal describes a five-year career development program to prepare Dr. Hongchao Guo for a career as
an independent investigator. This program will build on Dr. Guo’s background as a molecular stem cell biologist
by providing him expertise in bioinformatics, secretomics, and drug discovery techniques, and knowledge on
environmental health, immunology and cardiovascular biology to advance our understanding on how genetic
differences in individuals contribute to their susceptibility to smoking-related cardiovascular disease. Dr. Guo will
be mentored by Dr. Joseph Wu, Director of Stanford Cardiovascular Institute, who is an expert in cardiovascular
disease modeling using induced pluripotent stem cells (iPSCs). In addition, Dr. Guo will be co-mentored by Dr.
Kari Nadeau, Director of the Sean N. Parker Center for Allergy and Asthma Research at Stanford University,
who is an expert in studying aerosolized pollutants including tobacco smoke on the development of immune
dysfunction in primary immune disease, allergy and asthma. The K99 phase of Dr. Guo’s training will consist of
structured mentorship by the primary mentor and co-mentor, close interactions with collaborators,
complementary meeting with advisory committee members, a provocative research project, and a tailored
program for career development and transition. In Dr. Guo’s previous works, he has recapitulated key features
of nicotine-induced vascular dysfunction in patients using patient-specific iPSC-derived endothelial cell (iPSC-
EC). He has also shown that genetic variants in nicotinic acetylcholine receptor exacerbated nicotine-induced
EC dysfunction via increasing inflammation cytokines expression and apoptosis, which allow for analysis of the
molecular mechanism in iPSC-EC model with a level of depth and resolution never before achieved. With the
current advancement in high-throughput RNA sequencing and the cutting-edge secretomics and drug screening
technologies, Dr. Guo is in a unique position to stratify the patient risk of genetic variants in nicotinic receptors
for smoking-induced vascular diseases, and to study the potential mechanisms, with the ultimate goal to discover
biomarkers and precise treatment for cardiovascular diseases and risks. In the K99 phase, Dr. Guo will generate
and characterize patient-specific and isogenic iPSC-EC models for studying the susceptibility of three different
nAChR variants to nicotine-induced vascular dysfunction (Aim 1). With the platform, Dr. Guo will then integrate
high-throughput RNA sequencing and cutting-edge secretomics technologies to define the key molecular basis
and secretomic biomarkers for the risk of these variants to smoking-mediated vascular diseases (Aim 2). In the
R00 phase, Dr. Guo will develop a screening platform to examine the beneficial effect of anti-inflammatory drugs
and screen mechanism-oriented small molecules in iPSC-EC carrying these risk variants (Aim 3). Collectively,
Dr. Guo’s proposed work wi...

## Key facts

- **NIH application ID:** 10895572
- **Project number:** 5R00HL150319-04
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Hongchao Guo
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $249,000
- **Award type:** 5
- **Project period:** 2023-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10895572

## Citation

> US National Institutes of Health, RePORTER application 10895572, Delineating the Genetic Susceptibility of Smoking-Induced Vascular Dysfunction (5R00HL150319-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10895572. Licensed CC0.

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