M.D. -National Taiwan University
Ph.D. -Academia Sinica and National Taiwan University Joint Ph.D. Program of Translational Medicine
- Associate Professor, Graduate Institute of Medical Genomics and Proteomics, Medical College, National Taiwan University
- Attending Physician, Department of Endocrinology and Metabolism, National Taiwan University Hospital
- Vice CEO, Center for Bariatric and Metabolic Surgery, National Taiwan University Hospital
We focused on East Asian-specific genetic variants of type 2 diabetes, obesity, fatty liver, and kidney diseases. We use transgenic mice to dissect the molecular mechanism, develop small-molecular drugs, and conduct clinical trials.
East Asians are relatively genetically isolated. We participated in large-scale East Asian whole-genome scanning cooperation projects, such as TOPMed and SAPPHIRe. We discovered several novel East Asian-specific genetic variants for diabetes and obesity, such as the acetaldehyde dehydrogenase (ALDH2) mutation (E487K) and Canton-type G6PD genetic mutations.
We found that the ALDH2 East Asian-specific knockin mice developed obesity, abnormal glucose homeostasis, fatty liver, impaired renal function, and cardiomyopathy. We collaborated with Stanford University and pharmaceutical companies to develop potent ALDH2 activators which can scavenge harmful aldehydes and rescue these pathological conditions in mice. Among them, the preventive effect of acute kidney injury of ALDH2 activators will enter the second phase of clinical trials. We are also testing the therapeutic effects of small-molecule G6PD activators that can reverse obesity, abnormal glucose homeostasis, cardiomyopathy, and nephropathy caused by the Canton-type G6PD mutation in mice.
In addition, we also identified endogenous PPARγ ligands and used genetic knockout mice to confirm that increasing the endogenous PPARγ ligand can reduce obesity, fatty liver, and improve glucose homeostasis without the side effect of synthetic PPARγ ligands (thiazolidinediones) such as obesity, water retention, and osteoporosis. We further develop small-molecule PTGR2 inhibitors that can increase endogenous PPARγ ligands, improve glucose homeostasis, and reduce obesity and fatty liver in mice.
A common East-Asian ALDH2 mutation causes metabolic disorders and the therapeutic effect of ALDH2 activatorsNature Communications, Sep 25, 2023
ER ribosomal-binding protein 1 regulates blood pressure and potassium homeostasis by modulating intracellular renin traffickingJournal of Biomedical Science, Feb 19, 2023