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Research Outline      2016-07-20 14:09:51

The major research interest of my lab is in exploring the molecular basis of human diseases using the tools or concepts of stem cells. My research in the past five years is focused on two main areas. First, we have been establishing disease-specific induced pluripotent stem cells (iPSCs) or induced neurons for disease modeling in vitro and for drug screening. The successful examples include the establishment of human Pompe disease-specific iPSCs, which has been published in Human Molecular Genetics 2011. Currently we are developing disease-specific iPSCs for varied diseases, such as genetic heart diseases. We are also exploring the function of some novel mutated genes found in these diseases using embryonic stem cells/iPSCs-derived cardiomyocytes. For the second part, we have been exploring the roles of serine proteases, the substrates, and the inhibitors in controlling the fate of stem cells. We are also interested in understanding how these molecules are involved in causing human diseases when they are mis-regulated. A good example is HGFA and its inhibitors HAI-1/-2 in liver development; the former is capable of enhancing the hepatocyte differentiation from hepatic progenitor cells, while the later two play an exactly opposite role. Moreover, the overexpression of HAI-1/-2 may promote the progression of certain types of cholangiopathy, such as biliary atresia. Currently, we are trying to identify the key serine proteases/inhibitors that play decisive roles in controlling differentiation of stem cells using systemic methods that include functional proteomics.