Chia‐Hung Yen

My interests are mainly on developing preventive and therapeutic agents for metabolic disorders, cancer and new emerging pathogens from natural occurring substances and synthetic compounds by using high-throughput and high content screening system. I am the Chief Investigator of Natural Product Libraries and High-Throughput Screening Core (NPS Core) facility. NPS Core provides unique plant extract libraries, helps users/collaborators to build up phenotype-based or target-based screening assays, provides high-throughput screening and active component identification services. In addition to HTS services, my lab works on drug discovery for fatty liver, anti-oxidative response regulation, and influenza infection. Fatty liver, a condition of too much triglyceride fat accumulate in liver cells, can cause the death of hepatocytes and non-alcoholic steatohepatitis (NASH), then lead to hepatic fibrosis and cirrhosis, thus increase the risk of hepatocellular carcinoma (HCC). Non-alcoholic fatty liver disease (NAFLD) has become the most frequent liver disease during the past decades in developed and developing countries. The prevalence of NAFLD is now around 30% in Taiwan and is growing rapidly. Thus, NAFLD is expected to be a huge burden for public health in the future. Therefore, understanding the molecular mechanisms from simple fatty liver to NASH to HCC will contribute to the development of novel diagnostic biomarkers and therapeutic methods. Despite the most efficient treatments are weight loss and exercise, pharmacological strategies are still urgently needed. We utilized a phenotypic assay in HTS to identify natural products that can reduce lipid accumulation in hepatic cells. We have identified several hit plants, and the active components and their molecular mechanisms of action are currently under investigation. The nuclear factor erytheroid-derived-2-like 2 (NRF2)‒Kelch-like ECH is the master regulator of redox and xenobiotic sensitive signaling that functions to protect cells against oxidative stress and environmental toxicants through the induction of cytoprotective genes. However, recent genetic analyses of human cancer revealed that NRF2 could be oncogenic and cause resistance to chemotherapy. Moreover, abnormally high expression of NRF2 is frequently seen in human tumor specimen and correlated with poor prognosis. Therefore, we aimed for identification of selected NRF2 regulators that specifically suppress NRF2 function in cancer cells but not in normal cells. Stable NRF2 reporter cells were established in both HCC and immortalized keratinocyte cell lines. Bidirectional NRF2 regulator was identified form a Taiwan indigenous plant by HTS. We also identified several synthetic molecules as normal cell specific NRF2 inducers. In addition to investigate the underlying molecular mechanisms, the discovery of cancer specific NRF2 inhibitors is still in progress.