Faculty Profile

The major research interest in our laboratory is the mechanisms of the JAK-STAT signaling pathway in lymphomagenesis. We previously studied primary mediastinal and Hodgkin lymphoma, both of which share biological and molecular features. One common genetic alteration in these two cancers is an amplification of the chromosome 9p24 region where JAK2 resides. JAK2 and the co-amplified JMJD2C, a gene encoding histone demethylase, cooperate to promote cancer cell survival. The molecular mechanism of this synergism is histone modifications with H3K9 demethylation by JMJD2C and H3Y41 phosphorylation by JAK2, both of which lead to opening up chromatin structure for transcription of their target genes. Some of JAK2 target genes will be potential molecular targets since their expression is required for cancer cell survival or can evade tumor immunity. Recently, we have extended this finding and discovered a similar epigenetic mechanism by the JAK1 kinase in diffuse large B-cell lymphoma. We will employ a multidisciplinary approach, using biochemistry, RNA interference, next-generation sequencing (including ChIP-seq and RNA-seq), and systems biology methods, to identify JAK1 target genes in this lymphoma and to investigate crosstalk between JAK1 and other signaling pathways, such as NF-?B.

•Lixin Rui, Roland Schmitz, Michele Ceribelli, and Louis M. Staudt. Malignant pirates of the immune system (review article). Nature Immunology 2011; 12 (10): 933-940.
•Lixin Rui, N. C. Tolga Emre, Michael J. Kruhlak, Hye-Jung Chung, Christian Steidl, et al. Cooperative epigenetic modulation by cancer amplicon genes. Cancer Cell 2010; 18: 590-605.