My long term goal is to reveal novel functions of autophagy in normal cellular physiology and pathology through the analysis of the double-membrane autophagosome and autophagic machinery using cell and animal models.
• Autophagy regulates cellular metabolism to protect cell from stress-caused damages through degradation machinery. Over 20 autophagy related genes (Atg) are responsible for two major ubiquitination-like conjugation systems. Accumulating evidence shows that autophagosome selectively recruits cargos (aggregated protein, damaged organelle, pathogen and microRNA) in cytosol, followed by fusion with the lysosome for degradation. In our studies, we are the first to reveal that autophagosome selectively recruit oncogenic microRNA (miR-224) and protein (Cyclin D1) to regulate the tumorigenesis of hepatocellular carcinoma. These data indicate that autophagosome recognizes and recruits specific molecules followed by degradation.
• Another function of autophagy called secretory autophagy (also called autosecretion or type III secretion) is getting more attention. Different from the traditional degradative autophagy, the recruited cytosolic molecules are carried by the double-membrane autophagosome and exported to extracellular environment. However, physiological and pathological role of secretory autophagy remains poorly understood.
1. 鑑定由分泌型細胞自噬所運送到細胞外微環境的蛋白與物質: Identification of the cargos
delivered to extracellular environment through secretory
2. 釐清降解型細胞自噬與分泌型細胞自噬之間的關聯性: Clarification of the relationship between degradative and secretory autophagy.
3. 藉由調控細胞自噬活性之藥物來發展對於癌症，糖尿病等相關疾病之治療策略: Regulation of autophagy for the therapy of tumorigenesis, diabetes mellitus and other diseases.