Kaifu Chen

Title : System methods to define master regulator of cell identity in development and diseases

Abstract:

A cell type is determined by the network function of its cell identity genes, including master transcription factors that govern the expression status of this network. Cell identity transition is fundamental in normal differentiation and development, whereas a cell that loses its normal identity may cause disease including cancers. Targeting the driver genes for an abnormal cell identity holds great promise for new therapy. However, our understanding of cell identity regulators is incomplete. Integrating over >10,000 genomic and epigenomic profiles, we uncovered that cell identity genes as a unique group are distinct from other genes in the mechanisms to regulate their expression. These including epigenetic mechanism from the regulation of transcription by chromatin modifications to the post-transcriptional regulation of gene expression by RNA modifications. These discoveries laid the foundation for us to develop novel machine learning techniques, which utilize expression regulation mechanisms for systematic identification of driver genes for normal cell differentiation. By applying these techniques to endothelial cell, we successfully recaptured reported endothelial lineage factors. The techniques further revealed new endothelial lineage regulators, which were experimentally verified as required for the maintenance of normal endothelial cell identity, the differentiation from iPSCs to endothelial lineage, and the development of blood vessels. Applying these techniques to cancer samples further revealed new tumor suppressors and oncogenes that were hard to identify by conventional mutation analysis methods. The driver genes identified by our new techniques will lead to new therapeutic targets and diagnostic markers, as successfully verified in cell, xenograft, and PDX model for cancers, and thus, will benefit numerous patients.

Audience Take Away: 

• Epigenetic regulation mechanism at cell identity genes.
• Artificial intelligence techniques to uncover cell identity genes.
• Cell identity regulation in cell differentiation and tissue development.
• Role of MECOM in endothelial cell identity regulation and cardiovascular diseases.

Biography:

Dr. Chen is a computational biologist interested in computational modeling of cell identity regulation. He received PhD degree from the renowned Beijing Institute of Genomics. Thereafter, he joined the Dan L Duncan Cancer Center at Baylor College of Medicine as a postdoctoral fellow. Dr. Chen started his bioinformatics lab as an Assistant Professor in the Cornell University Weill Cornell Medical College at Houston Methodist Hospital Research Institute, where he further became an Associate Professor and was designated as the founding Director to develop a Center for Bioinformatics and Computational Biology. Dr. Chen is currently an Associate Professor in the Harvard Medical School at Boston Children’s Hospital.