Jisun Paik
University of Washington, WA·Pharmacology
Obesity and its complications remain widespread, and safe drugs that can be taken long term are still in short supply. One place to intervene is vitamin A metabolism.
- Fields
Pharmacology
Physiology
Medicine & Clinical Research
- Topics
obesity
retinoic acid
vitamin A
- Grants
- 1 known grant, through Jun 2027
What they work on
- Test whether N42, a newly developed selective inhibitor of the retinoic acid-making enzyme ALDH1A1, suppresses weight gain in obese mice kept on a high-fat diet and accelerates weight loss in obese mice given reduced calories.
- Assess potential organ toxicity of N42 using standard clinical and toxicologic pathology protocols, addressing the side effects seen with the broad ALDH1A inhibitor WIN 18,446.
- Map metabolic consequences of losing ALDH1A1 by applying global metabolomics and gene expression profiling to N42-treated and Aldh1a1-knockout mice, and link metabolites and retinoid levels to drug efficacy as candidate biomarkers.
- Separate the roles of liver and fat using tissue-specific Aldh1a1 knockout mice, and use an adipocyte lineage mouse model to determine whether losing the enzyme in adults alters formation of new fat cells versus enlargement of existing ones.
- Identify tissue-autonomous functions of ALDH1A1 by combining a perifusion method that maintains living tissue under controlled nutrient flow with metabolomics and systems-biology analysis.
More about the research
Vitamin A is converted into retinoic acid, a signaling molecule that switches on genes controlling how the body handles sugar and fat and whether precursor cells become fat cells. Three related enzymes, ALDH1A1, ALDH1A2 and ALDH1A3, make retinoic acid in different tissues at different times. ALDH1A1 is the main one in liver and fat, two tissues central to metabolism, making it an appealing drug target.
Why it matters
Obesity and its co-morbidities affect large populations in the United States and worldwide, and existing long-term treatments are limited. By testing a selective ALDH1A1 inhibitor in mice and mapping its metabolic effects and possible organ toxicity, this work could validate a new drug target for obesity, provide a prototype compound, and identify biomarkers that would help select patients and monitor response in future clinical use.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Sona Kang
University of California-Berkeley, CA·Physiology
Define how FAM3D, a protein genetically linked to type 2 diabetes, suppresses heat production and mitochondrial function in mouse and human brown fat cells.
Margo Emont
University of Chicago, IL·Physiology·Early-career
Track how human adipocyte subpopulations change during weight loss, using single-nucleus RNA sequencing of fat tissue collected during and after bariatric surgery.
Diana Monsivais
Baylor College of Medicine, TX·Medicine & Clinical Research
Define how retinoic acid production by ALDH1A1 and ALDH1A3 controls stem cell regeneration and maturation in the endometrium, using new creERT2-tdTomato reporter mice for lineage tracing and transcriptomic studies in endometrial organoids.
The school
University of Washington: 81 labs on PI Pages, $1.7B a year on research, 694 research doctorates a year.
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