After I finished my clinical training in internal medicine at NTU, I attended the University of Washington for a PhD degree in genetics. There, I worked on the regulatory mutations of the human lipoprotein lipase gene (hLPL) in association with familial combined hyperlipidemia under the guidance of Professor Samir S. Deeb. In that line of research, I characterized the functional alterations of a few promoter mutations of the hLPL gene using various methods of molecular biology.
　　After my return to NTU for a faculty position and endocrine fellow training at the same time, I switched my research interest to obesity, diabetes mellitus (DM), insulin resistance, metabolic syndrome (MetS) and adipocyte biology. I was lucky at the time to have jumped straight into the genetic and clinical studies of adiponectin, a growing research focus worldwide, through my first few grant-based projects. Working with Professors Lee-Ming Chuang and Kuo-Chin Huang of NTU, I was able to publish quite a few interesting observations regarding adiponectin and kicked off my research career on a good note. Altogether, we found that hypo-adiponectinemia is a hallmark of the MetS and its related components, both in adults and adolescents. In my later work with Professor Chih-Jen Chang of National Cheng-Kung University, we also determined the genetic polymorphisms of adiponectin associated with obesity, insulin resistance, the MetS and DM in Taiwanese.
　　Along the way, many physicians from other diverse disciplines asked to join my lab for their PhD thesis. After I took on the first student, I soon began to feel that being an advisor to physicians outside my field was a distraction at best and a burden at worst to my research focus and efforts. But seeing as these PhD students had nowhere else to turn to, I simply could not just leave them alone. I decided to devote the efforts that I could spare to guide them. Therefore, I was able to publish many papers in various fields, including nuclear medicine, OBS & GYN, hearing, myostatin, neurology, cardiovascular and GI systems and even surgery. I also learned a lot from guiding them. I am especially proud this year, as my first two doctorate students, Drs. YW Wu and MJ Chen were just promoted to professorship this year respectively in National Yang-Ming University and NTU.
　　In the meantime, I was able to team up my very first master student Dr. PL Chen more than 15 years ago with Professor Tien-Chun Chang in NTU and Professor Cathy SJ. Fann in Academia Sinica to investigate the human genetics behind Graves’ disease in Taiwanese. We have discovered the associations of genetic variants in CTLA-4 and HLA regions with this auto-immune thyroid disease. This group was also the first in the world to report the risk HLA alleles for anti-thyroid drug-induced agranulocytosis, a potentially deadly side effect previously of unknown etiology. This finding was very soon replicated by others.
　　In the mist of these tangential but nonetheless valuable lures, I continue my journey on adipocyte biology and biomarker discovery. Based on our lab’s own observations, I postulated that reduced adiponectin gene expression is a biomarker of adipose tissue-specific insulin resistance. Using 3T3-L1 mouse adipocyte as a model and treatment of pro-inflammatory cytokine IL-1b to mimic insulin resistance, I performed a genetic screening under this condition that suppressed adiponectin expression. Among the genes in the list, we recently showed that knockdown of RNaseL gene reduced adipocyte differentiation and that reduced serum level of RNaseL was associated with the MetS. Furthermore, we also found that serum RNaseL level was reduced in gestational DM as well. Similarly, knockdown of Spot14 gene also reduced adipocyte differentiation. We also demonstrated that the serum Spot14 level was related to thyroid status, adiposity and serum triglycerides. Although it has already been fruitful and rewarding, my research journey will not end here and will hopefully continue to flourish in the company of my colleagues in endocrinology & metabolism at NTU.