Kuangyu Yen

Chinese Academy of Medical Sciences, China

My research interest lies in transcription regulation. Our goal is to understand how chromatin regulates transcription in a spatiotemporal manner and apply this knowledge towards better diagnosis and management of human diseases. We use the well-known hematopoietic development as both a technological and conceptual model. To date, we have identified a two-tipping point model to explain the dynamic progression of how cell fate transits using in house bioinformatic tools and in vitro differentiation system. We aim to gain an understanding of the molecular mechanisms that trigger this phenomenon. The influence of a range of factors, such as non-canonical nucleosomes and chromatin confirmation, on initiating the overcoming of tipping point was investigated to ascertain if transcription bursting and inflammation may potentially contribute to overcoming the first and second tipping point, respectively. Function is then assessed through CRISPR/Cas9-engineered depletion of factors, and through biochemical reconstitution of protein/DNA complexes on a genomic scale. Parallel strategies are being conducted in model human cell lines and clinical samples. We intend to identify the contributors that facilitate the tipping point overcoming and their treatment outcome so as to prevent precancer cells further mature into cancer cells.