Research Faculty

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uk30@cumc.columbia.edu
Education and Training
Ph.D. 1998, University of Cologne
Ulf Klein, PhD
Adjunct Associate Professor of Pathology & Cell Biology
Research Summary

The hallmark of the humoral immune response is the clonal selection of memory B cells and plasma cells that bind to their specific antigen with high-affinity, thus establishing life-long immunity to pathogens. This complex process takes place in the germinal centers (GC) of lymph nodes. However, the beneficial role of the GC B-cell reaction in immunity appears to be counterbalanced by its detrimental role in lymphomagenesis, since the majority of lymphomas seem to originate from B cells that are at the decision point of becoming a memory or a plasma cell.

The laboratory's research interests are focused on the elucidation of the molecular mechanisms that govern the differentiation of GC B cells into memory or plasma cells, and on the investigation as to how those mechanisms are disrupted in B-cell malignancies. Since genomic lesions in B cells can lead to the deregulated expression of developmentally important transcription factors - thereby disturbing the control of cellular processes such as proliferation, apoptosis or differentiation -, these studies are expected to provide insights into the oncogenic transformation of mature B-cell lymphomas and leukemias.

Dr. Klein has relocated to the University of Leeds, U.K., in January 2017
Selected Publications

Milanovic, M., N. Heise, N.S. De Silva, M.M. Anderson, K. Silva, A. Carette, F. Orelli, G. Bhagat, and U. Klein. (2016) Differential requirements for the canonical NF-B transcription factors c-REL and RELA during the generation and activation of mature B-cells. Immunol. Cell Biol. 2016 Oct 18. doi: 10.1038/icb.2016.95. [Epub ahead of print]

Chinen, T., A.K. Kannan, A.G. Levine, X. Fan, U. Klein, Y. Zheng, G. Gasteiger, Y. Feng, J.D. Fontenot, and A.Y. Rudensky. (2016) An essential role for IL-2 receptor in regulatory T cell function. Nat. Immunol. 17:1322-1333.

De Silva, N.S., M.M. Anderson, A. Carette, K. Silva, N. Heise, G. Bhagat, and U. Klein. (2016) Transcription factors of the alternative NF-kappaB pathway are required for germinal center B-cell development. Proc. Natl. Acad. Sci. USA. 113:9063-9068.

Vlantis, K., A. Wullaert, A. Polykratis, V. Kondylis, M. Dannappel, R. Schwarzer, P. Welz, T. Corona, H. Walczak, F. Weih, U. Klein, M. Kelliher, and M. Pasparakis. (2016) RIPK1 mediated epithelial cell death causes Paneth cell loss and intestinal inflammation in mice with epithelial NEMO deficiency. Immunity 44:553-567.

De Silva, N.S., K. Silva, M.M. Anderson, G. Bhagat, and U. Klein. (2016) Impairment of mature B-cell maintenance upon combined deletion of the alternative NF-kappaB transcription factors RELB and NF-κB2 in B cells. J. Immunol. 196:2591-2601.

Lin, W.-H. W., W.C. Adams, S.A. Nish, Y.-H. Chen, B. Yen, N.J. Rothman, R. Kratchmarov, T. Okada, U. Klein, and S. Reiner. (2015) Asymmetric PI3K signaling driving developmental and regenerative cell fate bifurcation. Cell Rep. 13: 2203-2218, 2015.

Klein, U., and Heise, N. (2015) Unexpected functions of nuclear factor-kappaB during germinal center B-cell development: implications for lymphomagenesis. Curr. Opin. Hematol. 22: 379-387.

De Silva, N.S., and U. Klein. (2015) Dynamics of B cells in germinal centres. Nat. Rev. Immunol. 15: 137-148.

Heise, N., N.S. De Silva, K. Silva, A. Carette, G. Simonetti, M. Pasparakis, and U. Klein. (2014). Germinal center B-cell maintenance and differentiation are controlled by distinct NF-kappaB transcription factor subunits. J. Exp. Med. 211:2103-2118.

Simonetti, G., M.T.S. Bertilaccio, P. Ghia, and U. Klein. (2014). Mouse models in the study of chronic lymphocytic leukemia pathogenesis and therapy. Blood 124:1010-1019.

Simonetti, G., A. Carette, K. Silva, H. Wang, N. De Silva, N. Heise, C.W. Siebel, M.J. Shlomchik, and U. Klein. IRF4 controls the positioning of mature B cells in the lymphoid microenvironments by regulating NOTCH2 expression and activity. J. Exp. Med. 210: 2887-902, (2013)

Ochiai, K., M. Maienschein-Cline, G. Simonetti, J. Chen, R. Rosenthal, R. Brink, A.S. Chong, U. Klein, A.R. Dinner, H. Singh, and R. Sciammas. Transcriptional regulation of germinal center B and plasma cell fates by dynamical control of IRF4. Immunity, 38:918-929, (2013)

De Silva, N., G. Simonetti, N. Heise, and U. Klein. The diverse roles of IRF4 in late germinal center B-cell differentiation. Immunol. Rev. 247:73-92, (2012)

Lia, M., A. Carette, H. Tang, Q. Shen,T. Mo, G. Bhagat, R. Dalla-Favera, and U. Klein. Functional dissection of the chromosome 13q14 tumor-suppressor locus using transgenic mouse lines. Blood 119:2981-2990, (2012)

Klein, U., M. Lia, M. Crespo, R. Siegel, Q. Shen, T. Mo, A. Ambesi-Impiombato, A. Califano, A. Migliazza, G. Bhagat, and R. Dalla-Favera. The DLEU2/miR-15a/16-1 cluster controls B-cell proliferation and its deletion leads to chronic lymphocytic leukemia. Cancer Cell, 17: 28-40, (2010)

Zheng, Y., A. Chaudhry, A. Kas, P. deRoos, J.M. Kim, T.-T. Chu, L. Corcoran, P. Treuting, Klein, U., and A.Y. Rudensky. Regulatory T-cell suppressor program co-opts transcription factor IRF4 to control Th2 responses. Nature, 458:351-356, (2009)

Klein, U., and R. Dalla-Favera. Germinal centres: role in B-cell physiology and malignancy. Nat. Rev. Immunol. 8:22-33, 2008

Klein, U., S. Casola, G. Cattoretti, Q. Shen, M. Lia, T. Mo, T. Ludwig, K. Rajewsky, and R. Dalla-Favera. Transcription factor IRF4 controls plasma cell differentiation and class switch recombination. Nat Immunol. 7:773-782, (2006)

Klein, U., Y. Tu, G.A. Stolovitzky, J.L. Keller, J. Haddad, V. Miljkovic, G. Cattoretti, A. Califano, and R. Dalla-Favera. Transcriptional analysis of the germinal center reaction. Proc. Natl. Acad. Sci. USA. 100:2629-2644, (2003)

Klein, U., Y. Tu, G.A. Stolovitzky, M. Mattioli, G. Cattoretti, H. Husson, A. Freedman, G. Inghirami, L. Cro, L. Baldini, A. Neri, A. Califano, and R. Dalla-Favera. Gene expression profiling of B-cell chronic lymphocytic leukemia reveals a homogeneous phenotype related to memory B-cells. J. Exp. Med. 194:1625-1638, (2001)

Honors and Awards

2000 EMBO Long Term Fellowship

2000 HFSP Long Term Fellowship
Committees , Council, and Professional Society Memberships

American Society of Hematology
Keywords

B-cell lymphomagenesis, Germinal center reaction, B-cell development

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