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Academic Talk: The Pivotal Role of Hippo/YAP in Stem Cell Pluripotency
Ian Y. Lain Assistant Professor, Lamar University Google Scholar
Dr. Lian is a trained bioengineer with expertise in gene expression assays(microarray, qPCR and Illumina sequencing platform), accumulated over 10 years of experience in designing and developing cDNA & Oligo based high-throughput detection platforms. He is also experienced in manipulation, characterization and analysis of multiple stem/iPS cell lines. During graduate training under the supervision of Dr. Shu Chien, he has focused on the optimization, algorithm development and data analysis for various high-throughput gene expression assays and cross-platform comparison/validation. For his postdoctoral research, he worked under the mentorship of Dr. Kun-Liang Gaun and investigate the role of Hippo/YAP signaling pathway. His study has established the pivotal roles of YAP transcription coactivator in cancer and stem cells, leading to the discoveries in novel therapeutic targets for cancer and inflammatory diseases. As an independent investigator for the past two years, he combined basic science and engineering approaches to study the effect of cellular microenvironment on the metastatic potential of cancer cells.
Abstract The Hippo signaling pathway has recently been recognized as an important player in both organ size control and tumorigenesis, which are physiological and pathological processes that share common cellular signaling mechanisms. In this study, we report that the target of Hippo pathway kinase cascade, Yes-Associated-Protein (YAP), is inactivated during ES cell differentiation as indicated by the decreased protein levels and increased phosphorylation. Consistently, YAP is elevated during iPS cell reprogramming. YAP knockdown leads to a loss of ES cell pluripotency while ectopic expression of YAP prevents ES cell differentiation and maintains stem cell henotypes even under differentiation conditions. Moreover, YAP directly binds to promoters of a large number of genes known to be important for stem cells and stimulates their expression. Our observations establish a critical role of YAP in maintaining stem cell pluripotency.