Rafael C. Casellas, Ph.D.

Senior Investigator

Laboratory of Lymphocyte Nuclear Biology


Building 10, Room 13C103D
10 Center Drive
Bethesda, MD 20814



Research Topics

Dr. Casellas is a molecular biologist focusing on how nuclear events (e.g. transcription, epigenetics, recombination) drive cellular development and transformation, particularly of B lymphocytes. To explore these questions his laboratory has developed genome editing, genomics, and bioinformatic tools. Some highlights of their research are the discovery of transcriptome amplification, whereby the transcription program of G0 lymphocytes is globally and proportionally amplified during the immune response. They have also helped resolve the long-standing question of why certain oncogenes become translocated to antibody gene loci in human B cell tumors. In 2010, Dr. Casellas organized the NIH Regulome Project, a collaborative program between intramural and extramural investigators that seeks to elucidate mechanisms of gene expression. These efforts have revealed that oncogenes expressed in most tissues (e.g. Myc, Pim1) often change their entire enhancer repertoire during development, leading to differential promoter activity. In addition, their studies have shed light on how nuclear architecture regulates transcription, and how architectural enzymes can drive the formation of chromosomal translocations in some human cancers. More recently, they have solved the structure of the megadalton Mediator complex which provides insights into its function at regulating Pol II activity in mammalian cells.


Rafael Casellas received a Ph.D. in Molecular Immunology from the Rockefeller University in 2002, where he worked in the laboratory of Michel Nussenzweig. From 2002 to 2003, he did postdoctoral training with David Baltimore at the California Institute of Technology. In December 2003, Dr. Casellas moved to the NIAMS where he is currently a senior investigator and head of the Laboratory of Lymphocyte Nuclear Biology. Dr. Casellas is also serving as head of the NIH Regulome project.

Selected Publications

  1. El Khattabi L, Zhao H, Kalchschmidt J, Young N, Jung S, Van Blerkom P, Kieffer-Kwon P, Kieffer-Kwon KR, Park S, Wang X, Krebs J, Tripathi S, Sakabe N, Sobreira DR, Huang SC, Rao SSP, Pruett N, Chauss D, Sadler E, Lopez A, Nóbrega MA, Aiden EL, Asturias FJ, Casellas R. A Pliable Mediator Acts as a Functional Rather Than an Architectural Bridge between Promoters and Enhancers. Cell. 2019;178(5):1145-1158.e20.

  2. Zhang X, Zhang Y, Ba Z, Kyritsis N, Casellas R, Alt FW. Fundamental roles of chromatin loop extrusion in antibody class switching. Nature. 2019;575(7782):385-389.

  3. Vian L, Pękowska A, Rao SSP, Kieffer-Kwon KR, Jung S, Baranello L, Huang SC, El Khattabi L, Dose M, Pruett N, Sanborn AL, Canela A, Maman Y, Oksanen A, Resch W, Li X, Lee B, Kovalchuk AL, Tang Z, Nelson S, Di Pierro M, Cheng RR, Machol I, St Hilaire BG, Durand NC, Shamim MS, Stamenova EK, Onuchic JN, Ruan Y, Nussenzweig A, Levens D, Aiden EL, Casellas R. The Energetics and Physiological Impact of Cohesin Extrusion. Cell. 2018;173(5):1165-1178.e20.

  4. Ba Z, Lou J, Ye AY, Dai HQ, Dring EW, Lin SG, Jain S, Kyritsis N, Kieffer-Kwon KR, Casellas R, Alt FW. CTCF orchestrates long-range cohesin-driven V(D)J recombinational scanning. Nature. 2020;586(7828):305-310.

  5. Xu J, Xu K, Jung S, Conte A, Lieberman J, Muecksch F, Lorenzi JCC, Park S, Schmidt F, Wang Z, Huang Y, Luo Y, Nair MS, Wang P, Schulz JE, Tessarollo L, Bylund T, Chuang GY, Olia AS, Stephens T, Teng IT, Tsybovsky Y, Zhou T, Munster V, Ho DD, Hatziioannou T, Bieniasz PD, Nussenzweig MC, Kwong PD, Casellas R. Nanobodies from camelid mice and llamas neutralize SARS-CoV-2 variants. Nature. 2021;595(7866):278-282.

This page was last updated on September 15th, 2021