Rafael Casellas, Ph.D.

Dr. Rafael Casellas received his Ph.D. in Molecular Immunology from the Rockefeller University in 2002. There, he worked under Dr. Michel Nussenzweig to study 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, where he continued his studies of B cell activation. In December 2003, Dr. Casellas moved to the Laboratory of Molecular Immunogenetics of NIAMS to create the Genomics & Immunity Group, where he is currently a senior investigator and branch chief. Dr. Casellas is also serving as an adjunct investigator at the Center for Cancer Research, NCI.

Rafael’s laboratory is interested in understanding how nuclear events (e.g. transcription, epigenetics, recombination) drive early development and peripheral activation of B lymphocytes. A recurrent theme has been exploring the role of V(D)J recombination, somatic hypermutation, and class switching in B cell tumorigenesis. Another emphasis has been the application of genome editing, genomics, and bioinformatic tools to explore B cell biology.

His most important findings include the discovery, together with David Levens (NCI), of transcriptome amplification, a process whereby the transcription program of naïve lymphocytes is globally and proportionally amplified as they engage in the immune response. Rafael’s lab also resolved a long-standing question about the origin of chromosomal translocations in B cell lymphomas. They showed that these genetic aberrations result from promiscuous DNA damage by AID, the immunoglobulin gene mutator, rather than the frequency by which translocating genes interact. Another key finding was that genes expressed in most tissues (e.g. Myc, Pim1) often change their entire enhancer repertoire during development, leading to differential promoter activity.

Rafael has organized collaborative projects between intramural and extramural laboratories using the latest technology. In 2011, he established the NIH Mouse Regulome Project, a program that seeks to elucidate how gene expression is regulated in the mouse genome using 3C, genome editing, genomics, and nanoscopy. This dynamic collaboration has so far produced 4 publications in Cell. Currently, the Casellas lab is also contributing to the 4D Nucleome Project, an NIH Director Program that explores the role of nuclear architecture in organismal development.