Hongchao Guo
University of Utah, UT·Physiology·Early-career
Smoking damages blood vessels, but not everyone's vessels suffer equally. Part of the difference is inherited: common variants in genes that handle toxic chemicals or respond to nicotine can make the cells lining blood vessels more vulnerable to tobacco smoke.
- Fields
Physiology
Pharmacology
Medicine & Clinical Research
- Topics
ALDH2*2
endothelial dysfunction
cardiovascular disease
- Grants
- 2 known grants, through Jan 2031
What they work on
- Test whether a signaling chain from reactive oxygen species through the transcription factors FOXO1 and KLF5 to IL-18 and IL-1β drives endothelial dysfunction, using iPSC-derived endothelial cells and transgenic mice carrying the ALDH2*2 variant.
- Screen small molecules that target the ROS-FOXO1-KLF5 axis in cigarette smoke-exposed ALDH2*2 endothelial cells to see whether blocking this pathway restores endothelial function.
- Determine how the nuclear pore protein NUP210 interacts with the LINC complex to shape the response to blood-flow shear stress, mapping H3K27me3 marks on extracellular matrix genes with RNA-seq, ATAC-seq, ChIP-seq and single-cell RNA-seq.
- Generate patient-specific and isogenic iPSC-derived endothelial cell lines for three nicotinic acetylcholine receptor variants and compare their susceptibility to nicotine-induced vascular dysfunction.
- Define the molecular basis and secreted biomarkers of risk for these nicotinic receptor variants by combining high-throughput RNA sequencing with secretomics of the proteins the cells release.
- Build a drug screening platform in variant-carrying endothelial cells to test anti-inflammatory agents and mechanism-oriented small molecules against smoking-related vascular dysfunction.
More about the research
Work here takes blood or skin cells from people carrying such variants, reprograms them into induced pluripotent stem cells (iPSCs, cells that can be turned into nearly any tissue), and then turns them into endothelial cells, the cells that form the inner lining of blood vessels. That gives a human, patient-specific system in which to ask how a particular genetic background plus smoke exposure produces vascular disease, and to look for drugs that intervene.
Why it matters
Cardiovascular disease remains the leading cause of death worldwide, and smoking is a major contributor whose harm depends partly on a person's genes. By showing whether and how tobacco is especially dangerous for carriers of the ALDH2*2 variant, shared by roughly 540 million people, and of nicotinic receptor variants, this work could support precision-medicine advice about smoking risk and yield secreted biomarkers plus drug candidates aimed at protecting blood vessel linings.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Daniel Garry
University of Minnesota, MN·Medicine & Clinical Research
Test whether GFP-labeled pig stem cells with mismatched MHC immune genes can rescue pig embryos lacking the heart-building genes NKX2-5, TBX5 and HAND2, using blastocyst complementation.
Paul W. Burridge
Northwestern University, IL·Pharmacology
Test whether susceptibility to nilotinib-induced artery disease is intrinsic to patients' cells by generating induced pluripotent stem cell lines from 100 nilotinib-treated patients, differentiating them to endothelial cells, and comparing drug responses across six validated assays.
Dwight Stambolian
University of Pennsylvania, PA·Genetics
Differentiate eight patient-derived iPSC lines into retinal pigment epithelium, four with CFH risk alleles and four gene-corrected isogenic controls, and quantify mRNA, protein and function of complement components, regulators and receptors.
The school
University of Utah: 58 labs on PI Pages, $789M a year on research, 366 research doctorates a year.
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