本實驗室主要研究目的有以下幾個大方向:

1. 特發性肺纖維化(idiopathic pulmonary fibrosis, IPF)是一種特殊的原因不明之慢性纖維化間質性肺炎，病灶局限於肺部。它的特點是呼吸困難和肺功能漸進性惡化，且預後很差。IPF發病率在全世界迅速上升，主要由肺器官中一連串由發炎引發的纖維化過程所造成。尤其最近，大多數嚴重的 COVID-19 患者會出現過度發炎的症狀和肺炎，COVID-19 的主要危險因素與 IPF相同，即老年、男性以及合併症如高血壓和糖尿病。目前用作IPF的一線治療藥物有pirfenidone 和 nintedanib，但由於存在多種副作用，使病人的生活質量和生存率均未得到明顯改善。因此，需要開發IPF肺纖維化的新型治療方法，以提高患者的生存率。本實驗室的目的是研究針對 TGF-β 相關機制之抗肺纖維化的新型藥物，並確定這些抗肺纖維化作用的藥物之分子機制。新藥的治療活性將在細胞/動物模型（IPF 細胞/肺纖維化小鼠肺切片）實驗中進行探討。

2. 肝炎病毒 (Hepatitis virus): 我們的研究在於探討肝炎病毒之生活史及其致病機轉，希望透過對這些病毒之瞭解，能開發治療肝炎病毒之新藥。B型肝炎病毒(HBV)會造成人類肝臟急性或慢性的感染；並伴隨著嚴重的肝臟疾病，例如肝硬化及肝癌。D型肝炎病毒(HDV)會與B型肝炎病毒(HBV)共同感染（co-infection）或重疊感染（super-infection），引起嚴重的慢性肝炎，甚至猛爆性肝炎。我們希望瞭解在B型及D型肝炎病毒感染初期，研究宿主細胞運輸作用參與在B型及D型肝炎病毒生活史中的功能角色，進一步，我們也將研究B型及D型肝炎病毒在宿主細胞上的受體NTCP蛋白與病毒之間的作用關係。透過這個研究，除了有助於B型及D型肝炎病毒致病機轉的了解之外，並且可作為病毒藥物開發的模式。

3. 脂肪肝(Fatty liver disease)/代謝症候群(Metabolic syndrome): 目前已知肥胖和胰島素失調與許多疾病間存在關聯性，例如心血管疾病、第二型糖尿病、脂肪肝等等，這類疾病常涉及脂類代謝異常或醣類代謝異常。舉例而言，脂肪肝屬於非酒精性脂肪肝疾病的初始階段，是一種現代人常見的代謝症狀，主要是由脂質代謝失衡所造成。目前已有為數不少的臨床經驗顯示，脂肪肝會導致肝硬化，並且伴隨著脂肪性肝炎及肝壞死等問題的發生。我們的研究在於發展新藥在治療代謝疾病之用途，利用疾病小鼠之模型，希望可以改善多種新陳代謝疾病。

4. 益生菌與腸道菌相(Healthy Food and Gut Microbiota): 益生菌或健康食品針對腸道菌相之影響，透過健康食品來穩定有益於宿主代謝的腸道菌叢生態，此機制將可證明健康食品是否為好的益生質，可應用於肥胖及相關代謝疾病的治療或預防。本實驗室希望瞭解健康食品對抗脂肪肝/代謝症候群的機制，並配合其低毒性之特性，將有助於評價健康食品作為脂肪肝治療與降低血脂血糖的可能性，可以作為將來開發植物新藥的基礎。另外，我們也將掌握健康食品具有抑制脂肪肝及肥胖效果的成份，改善腸道菌相的關鍵方法，完成效果驗證; 也將利用我們建立的腸道菌相分析平台，積極發展健康食品或中草藥之治療疾病導向的微生物群系技術。

1. Idiopathic pulmonary fibrosis (IPF) is a progressive inflammatory disorder driven by a fibrotic cascade in the lungs in a sequential manner. IPF incidences were raising rapidly across the world. Recently, most severe COVID-19 patients develop hyper-inflammation and pneumonia. The major risk factors for severe COVID-19 are shared with IPF, namely increasing age, male sex, and comorbidities such as hypertension and diabetes. However, the role of antifibrotic therapy in patients with IPF is poorly defined. FDA approved pirfenidone and nintedanib (tyrosine kinase inhibitors) are being used as a first-line treatment drugs for IPF, however, neither the quality of life nor survival rates have been improved because of multiple side effects. Thus, the development of novel therapeutic approaches targeting TGF-β mediated cascade of fibrotic events is urgently needed to improve the survival of the patients.The aim of our lab is to investigate and validate the anti-fibrotic properties of novel drugs against TGF-β mediated fibrosis in in vitro and in vivo models and to determine the molecular mechanisms that mediate these anti-fibrotic effects.

2. Hepatitis B virus (HBV) causes acute and chronic infections in humans; such infections are often associated with severe liver diseases, including cirrhosis and hepatocellular carcinoma (HCC). Hepatitis delta virus (HDV) causes fulminant hepatitis and progressive chronic liver cirrhosis in patients superinfected or coinfected with HBV. We examined the roles of clathrin-mediated trafficking pathway involved in the life cycle of HBV/HDV. In addition, the receptor on the plasma membrane which is required for the infection of HBV/HDV is NTCP. We have established HBV/HDV infection model in vitro and in vivo. Our model will help us to develop new drugs for treatment of HBV/HDV infection. Our study suggests new strategies for manipulating HBV/HDV for therapeutic purposes in treating disorders associated with liver injury and cirrhosis.

3. Fatty liver and metabolic syndrome: Obesity and dysregulated insulin action in the liver are strongly associated and are currently a worldwide health problem. Fatty liver, the initial stage of nonalcoholic fatty liver disease (NAFLD), is a common metabolic symptom, and is caused by an imbalance of lipid metabolism. The purpose of our proposal is to develop drugs for metabolic syndrome. We will design a process of pharmacology experiments for development of new drugs. In addition, we will complete additional safety evaluation for new drugs.

4. Healthy Food and Gut Microbiota: The biological activity of healthy food or herbal medicines to affected the gut microbiota. The gut microbiota is correlated to host metabolism, and healthy food or herbal medicines will be proved to be a good prebiotics. Therefore, we try to understand the mechanism of healthy food or herbal medicines against fatty liver, and with its low toxicity and non-mutagenic nature, it will help to evaluate the possibility of healthy food or herbal medicines to be developed as new botanical drugs. In addition, we will also grasp the key ingredients of healthy food or herbal medicines that have the effect on inhibiting fatty liver and obesity, and improve the gut microbiota. The gut microbiota analysis platform will be further used as the technology to evaluate healthy food or traditional Chinese herbal medicines for the treatment of diseases.