BIOGRAPHICAL SKETCH Rafael Casellas Branch Chief, Genomics

BIOGRAPHICAL SKETCH
NAME
POSITION TITLE
Rafael Casellas
Branch Chief, Genomics & Immunity
NIAMS-NCI/NIH
INSTITUTION AND LOCATION
DEGREE
YEAR(s)
FIELD OF STUDY
Brigham Young University (USA)
Rockefeller University (PI. Michel Nussenzweig)
Caltech (PI. David Baltimore)
National Institutes of Health
National Institutes of Health
National Institutes of Health
Bachelor’s degree
Ph.D.
Post-doc
Tenure track
Senior Investigator
Branch Chief
1992-1996
1996-2002
2002-2003
2004-2011
2011-2013
2013-present
Chemistry
Molecular Immunology
Molecular Biology
Genomics & Immunity
Genomics & Immunity
Genomics & Immunity
A. Personal Statement
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, gene targeting, transgenic techniques, as
well as genomic and bioinformatic tools.
B. Positions and Honors
1996 Hypercube Scholar (best graduating student)
1996-1997 NIH Predoctoral Fellowship
1997-2001 NSF Predoctoral Fellowship
2002-2003 NIH Postdoctoral Fellowship
2003-2004 NCI Mentored Career Development Award (K01)
2008 Member of the Henry Kunkel Society
2008 NIH MERIT Award
2010 NIH Director’s Award
C. Selected publications
Casellas, R., Shih, T. A., Kleinewietfeld, M., Rakonjac, J., Nemazee, D., Rajewsky,
K., and Nussenzweig, M. C. (2001). “Contribution of receptor editing to the antibody
repertoire.” Science, 291(5508), 1541-4.
Petersen, S.*, Casellas, R.*, Reina-San-Martin, B., Tang Chen, H., Difilippantonio,
M.J., Wilson, P., Hanitsch, L., Celeste, A., Muramatsu|, M., Pilch, D.R., Redon, C.,
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Ried, T., Bonner, W.M., Honjo, T., Nussenzweig, M.C., Nussenzweig, A. (2002).
“AID is required to initiate Nbs1/g-H2AX focus formation and mutations at sites of
class switching.” Nature, 414, 660-5.
*First author equal contribution
Casellas, R., Jankovic, M., Meyer, G., Gazumyan, A., Luo, Y., Roeder, R.G.,
Nussenzweig, M.C. (2002) “OcaB is required for normal transcription and V(D)J
recombination of a subset of immunoglobulin k genes.” Cell, 110: 575-585.
Kruhlak, M., Crouch, E. E., Orlov, M., Montaño, C, Gorski, S.A., Nussenzweig, A.,
Misteli, M., Phair, R.D., Casellas, R. (2007) "The ATM repair pathway abolishes Pol
I transcription in response to chromosome breaks." Nature, 447:730-734.
Klemm, L., Duy, C., Iacobucci, I., Kuchen, S., von Levetzow, G., Feldhahn, N.,
Henke, N., Li, Z., Hoffmann, T.K., Kim, Y., Hofmann, W., Jumaa, H., Groffen, J.,
Heisterkamp, H., Martinelli, G., Lieber, M., Casellas , R.*, Müschen, M.* (2009). The
B cell Mutator AID promotes B lymphoid blast crisis and drug-resistance in chronic
myeloid leukemia. Cancer Cell, 16:1-14.
*Last author equal contribution
Ji, Yanhong., Corbett, E., Resch, W., Yamane, A., Casellas, R.*, Schatz, D.* (2010).
The in vivo pattern of binding of RAG1 and RAG2 to antigen receptor loci. Cell,
141:419-431
*Corresponding author
Kuchen, S., Resch, W., Yamane, A., Kuo, N., Chakraborty, T., Wei, L., Laurence, A.,
Li, Z., Hu-Li, J., Lu, K., Dubois, W., Kitamura, Y., Sun, H., Muljo, S., Potter, M.,
Schwartzberg, P.L., Paul, W.E., O’Shea, J., Rajewsky, K., Casellas, R. (2010).
Regulation of microRNA expression and abundance during lymphopoiesis.
Immunity 32:1-12 .
Daniel, J.A., Santos, M.A., Wang, Z., Zang, C., Jancovic, M., Gazumyan, A.,
Schwab, K.R., Tamane, A., Filsuf, D., Cho, Y-W., Ge, K., Nussenzweig, M.C.,
Casellas, R., Dressler, G.R., Zhao, K., Nussenzweig, A. (2010). PTIP promotes
chromatin changes critical for immunoglobulin switch recombination. Science
329:917-23.
Pavri, R., Gazumyan, A., Klein, I., DiVirgilio, M., Jankovic, M., Ansara-Sobrinho, C.,
Resch, W., San-Martin, B.R., Barreto, V., Neiland, T., Root, D., Casellas, R.*,
Nussenzweig, M.C.* (2010). Activation Induced Cytidine Deaminase targets DNA at
sites of polymerase stalling by interaction with Spt5. Cell 143:1-12.
*Corresponding author
Yamane, A., Resch, W., Kuo, N., Li, Z., Sun, H-W., Robbiani, D.F., Nussenzweig,
M.C., Casellas, R. (2010). Deep-sequencing reveals the genomic targets of AID and
RPA in B lymphocytes. Nature Immunology 12:62-9.
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Klein, I. A., Resch, W., Jankovic, M., Oliveira, T., Yamane, A., Nakahashi, H., Di
Virgilio, M., Bothmer, A., Nussenzweig, A., Robbiani, D. F., Casellas, R.* and
Nussenzweig, M. C.* (2011) Translocation-Capture Sequencing Reveals the Extent
and Nature of Chromosomal Rearrangements in B Lymphocytes. Cell, 147:95-106.
*Corresponding author and equal contributor.
Fritz, J.H., O.L. Rojas, N. Simard, D.D. McCarthy, S. Hapfelmeier, S. Rubino, S.J.
Robertson, M. Larijani, J. Gosselin, Ivanov, II, A. Martin, R. Casellas, D.J. Philpott,
S.E. Girardin, K.D. McCoy, A.J. Macpherson, C.J. Paige, and J.L. Gommerman.
(2012). Acquisition of a multifunctional IgA+ plasma cell phenotype in the gut.
Nature 481: 199-203.
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. (2012) DNA damage defines sites of recurrent
chromosomal translocations in B lymphocytes. Nature 484:69-74.
Takahashi, H., Kanno, T., Nakayamada, S., Hirahara, K., Sciume, G., Muljo, S.A.,
Kuchen, S., Casellas, R., Wei, L., Kanno, Y., O'Shea, J.J. (2012). TGF-beta and
retinoic acid induce the microRNA miR-10a, which targets Bcl-6 and constrains the
plasticity of helper T cells. Nature Immunology 13, 587-595.
Nie, Z., Hu, G., Wei, G., Cui, K., Yamane, A., Resch, W., Wang, R., Green, D.R.,
Tessarollo, L., Casellas, R., Zhao, K., Levens, D. (2012). c-Myc Is a Universal
Amplifier of Expressed Genes in Lymphocytes and Embryonic Stem Cells. Cell 151,
68-79.
Yamane, A., D.F. Robbiani, W. Resch, A. Bothmer, H. Nakahashi, T. Oliveira, P.C.
Rommel, E.J. Brown, A. Nussenzweig, M.C. Nussenzweig, and R. Casellas. (2013).
RPA accumulation during class switch recombination represents 5'-3' DNA-end
resection during the S-G2/M phase of the cell cycle. Cell Reports 3:138-147.
Jankovic, M., N. Feldhahn, T.Y. Oliveira, I.T. Silva, K.R. Kieffer-Kwon, A. Yamane,
W. Resch, I. Klein, D.F. Robbiani, R. Casellas, and M.C. Nussenzweig. (2013).
53BP1 Alters the Landscape of DNA Rearrangements and Suppresses AID-Induced
B Cell Lymphoma. Molecular Cell 49(4):623-31.
Di Virgilio, M., E. Callen, A. Yamane, W. Zhang, M. Jankovic, A.D. Gitlin, N.
Feldhahn, W. Resch, T.Y. Oliveira, B.T. Chait, A. Nussenzweig, R. Casellas, D.F.
Robbiani, and M.C. Nussenzweig. (2013). Rif1 prevents resection of DNA breaks
and promotes immunoglobulin class switching. Science 339:711-715.
Barlow, J.H., R.B. Faryabi, E. Callen, N. Wong, A. Malhowski, H.T. Chen, G.
Gutierrez-Cruz, H.W. Sun, P. McKinnon, G. Wright, R. Casellas, D.F. Robbiani, L.
Staudt, O. Fernandez-Capetillo, and A. Nussenzweig. (2013). Identification of early
replicating fragile sites that contribute to genome instability. Cell 152:620-632.
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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.
(2013). Global regulation of promoter melting in naïve lymphocytes Cell, 153:988999.
Nakahashi, H., K-R. Kieffer-Kwon, W. Resch, L. Vian, D. Marrei, D. Stavreva, O.
Hakim, N. Pruett, S. Nelson, A. Yamane, J. Qian, W. Dubois, S. Welsh, R.D. Phair,
B.F. Pugh, V. Lobanenkov, G.L. Hager, and R. Casellas. (2013). A genome-wide
map of CTCF multivalency redefines the CTCF code. Cell Reports, 3, 1-12.
Kieffer Kwon K, Z. Tang, E. Mathe, J. Qian, M. Sung, G. Li, W. Resch, S. Baek, N.
Pruett, L. GrØntved, L. Vian, S. Nelson, O. Hakim, D. Reyon, A. Yamane, H. Nakahashi,
A. Kovalchuk, J. Zou, J.K. Joung, V. Sartorelli, C. Wei, X. Ruan, G.L. Hager, Y. Ruan,
and R. Casellas (2013). Interactome maps of mouse gene regulatory domains reveal
basic principles of transcriptional regulation. Cell, 155, 1466-1478 (In Press).
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