Rafael Casellas, Ph.D.

Rafael  Casellas, Ph.D.
Adjunct Investigator
Head, Genomics and Immunity Group, NIAMS

The major goal of our laboratory is to unravel the molecular mechanisms driving early development and peripheral activation of B lymphocytes. In particular, we are interested in the processes that assemble, diversify, and provide effector functions to antibody receptors, namely V(D)J recombination, somatic hypermutation, and class switching. Another major interest of our laboratory is to understand how deregulation of these reactions leads to B cell tumorigenesis. To achieve these goals, our laboratory is combining molecular biology, genome editing, mouse genetics, genomics and bioinformatic tools.

Visit the Casellas' Lab for more information.

Areas of Expertise
1) genomics 2) mouse genetics 3) B cell immunology 4) epigenetics

Contact Info

Rafael Casellas, Ph.D.
Center for Cancer Research
National Cancer Institute
Building 10, Room 13C103-D
Bethesda, MD 20892
Ph: 301-402-7858
rafael.casellas@nih.gov

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.

Scientific Focus Areas:
Genetics and Genomics, Immunology
View Dr. Casellas' Complete Bibliography.

Selected Recent Publications

  1. Qian, J., Wang, Q., Dose, M., Pruett, N., Kieffer-Kwon, K-R., Resch, W., Liang, G., Tang, Z., Mathé, E., Benner, C., Dubois, W., Nelson, S., Vian, L., Oliveira, T.Y., Jankovic, M., Hakim, O., Gazumyan, A., Pavri, R., Awasthi, P., Song, B., Liu, G., Chen, L., Zhu, S., Feigenbaum, L., Staudt, L., Murre, C., Ruan, Y., Robbiani, D.F., Pan-Hammarström, Q., Nussenzweig, M.C., and R. Casellas
    Cell. 159: 1524-1537, 2014. [ Journal Article ]
  2. Meng FL, Du Z, Federation A, Hu J, Wang Q, Kieffer-Kwon KR, Meyers RM, Amor C, Wasserman CR, Neuberg D, Casellas R, Nussenzweig MC, Bradner JE, Liu XS, and Alt FW
    Cell. 159: 1538-1548, 2014. [ Journal Article ]
  3. Kieffer-Kwon, K.-R., Z. Tang, E. Mathe, J. Qian, M.H. Sung, G. Li, W. Resch, S. Baek, N. Pruett, L. Grontved, L. Vian, S. Nelson, H. Zare, O. Hakim, D. Reyon, A. Yamane, H. Nakahashi, A.L. Kovalchuk, J. Zou, J.K. Joung, V. Sartorelli, C.L. Wei, X. Ruan, G. Hager, J. Ruan, and R. Casellas
    Cell. 155: 1507-1520, 2013. [ Journal Article ]
  4. Kouzine, F., D. Wojtowicz, A. Yamane, W. Resch, K.-R. Kieffer-Kwon, R. Bandle, N. Steevenson, H. Nakahashi, P. Awasthi, L. Feigenbaum, H. Menoni, J.H. Hoeijmakers, W. Vermeulen, H. Ge, T.M. Przyticka, D. Levens, and R. Casellas
    Cell. 153: 988-999, 2013. [ Journal Article ]
  5. Hakim, O., Resch, W., Yamane, A., Klein, I., Kieffer-Kwon, K-R., Jankovic, M., Oliveira, T., Bothmer, A., Voss, T.C., Ansarah-Sobrinho, C., Mathe, E., Liang, G., Cobell, J., Nakahashi, H., Robbianni, D., Nussenzweig., A., Hager, G.L., Nussenzweig, M.C., and Casellas, R.
    Nature. 484: 69-74, 2012. [ Journal Article ]
Name Position
Marei Dose Postdoctoral Fellow (Bioinformatics)
Kyong-Rim Kieffer-Kwon Research Fellow
Philippe Kieffer-Kwon Research Fellow
Jordan Krebs NIH UGSP Scholar
Ewy Mathe Staff Scientist (Bioinformatics)
Steevenson Nelson Biologist
Nathan Pruett Postdoctoral Fellow
Wolfgang Resch Staff Scientist (Bioinformatics)
Evan Stevens MD-PhD Student
Laura Vian Visiting Fellow
Jianliang Xu Postdoctoral Fellow