Dr Rafael Casellas, Chief, Genomics and Immunity Section and Acting Chief, Laboratory of Molecular Immunogenetics, NIAMS, National Institutes of Health. Adjunct Investigator at the Center for Cancer Research, National Cancer Institute, Bethesda, US.
A key finding of the ENCODE project is that the enhancer landscape of mammalian cellsundergoes marked alterations during ontogeny. However, the nature and extent of these changes are unclear. As part of the NIH Mouse Regulome Project, we have combined DNAseI hypersensitivity, ChIP-Seq, and ChIA-PET technologies to map the promoterenhancer interactomes of pluripotent ES cells and differentiated B lymphocytes. We confirm that enhancer usage varies widely across tissues. Unexpectedly, we find that this regulation extends to broadly-expressed genes, including Myc and Pim1 cell cycle regulators, which associate with an entirely different set of enhancers in ES and B cells. By means of highresolution CpG methylomes, genome editing, and digital footprinting we show that these enhancers recruit lineage-determining factors. Furthermore, we demonstrate that the loss or acquisition of enhancers during development directly modulate gene transcription levels. We propose that organisms rely on a dynamic enhancer landscape to control basic cellular functions in a tissue-specific manner.
Dr Rafael Casellas received his PhD in Molecular Immunology in 2002 from the Rockefeller University under Dr Michel Nussenzweig. There he studied the role of immunoglobulin gene expression and recombination in the establishment of B cell tolerance and peripheral activation. From 2002 to 2003 he did postdoctoral training with David Baltimore at the California Institute of Technology. In January 2004, Rafael was recruited to the National Institutes of Health to create the laboratory of Genomics & Immunity. In 2012 he was given tenure and in 2013 he became a branch chief. His laboratory combines mouse genetics, genomics, and bioinformatic tools to explore B cell development and tumorigenesis. For the past two years Rafael has also headed the NIH Mouse Regulome Project, an initiative that comprehensively characterizes gene regulatory domains and their connectivity in the mouse genome.