Lixin Rui, PhD

Portrait of Lixin Rui, PhD
Assistant Professor
Medicine
Address: 
4053 WIMR
1111 Highland Ave
Madison, WI 53705
Telephone: 
(608) 265-8525
Focus Groups: 
Cancer Biology
Immunology/Immunopathology
Education: 
PhD, Australian National University, Canberra, Immunology
Research Summary: 
Investigating the JAK-STAT signaling pathway in lymphoid malignancies; Identifying new molecular targets of this pathway for clinical applications.
Research Detail: 

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 change in these two cancers is an amplification of chromosome 9p24 region where JAK2 resides. JAK2 and the co-amplified JMJD2C, a gene encoding histone demethylase, cooperate to promote tumor growth. 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 gene transcription. Some of JAK2 target genes will be potential molecular targets since their expression is required for cancer cell survival. Recently, we have extended this finding and discovered a similar epigenetic mechanism by the other family member JAK1 in aggressive diffuse large B-cell lymphoma. We will employ a multidisciplinary approach, using biochemistry, RNA interference, DNA microarray, next-generation sequencing, and systems biology methods, to identify JAK1 target genes in this lymphoma.

Our interests also include investigation of the F-box protein FBXO10. Our recent work has characterized FBXO10 as a potential tumor suppressor. As the ubiquitin E3 ligase, FBXO10 targets the anti-apoptotic protein BCL2 for degradation. The gene FBXO10 is infrequently mutated in diffuse large-B cell lymphomas but has reduced expression in a vast majority of these patient samples. We will collaborate with Dr. Michael Gould to dissect FBXO10 function in vivo using FBXO10 knockout murine models established in his lab.

Selected Publications: 
Li Y*, Bouchlaka MN*, Wolff J, Grindle KM, Lu L, Qian S, Zhong X, Pflum N, Jobin P, Kahl BS, Eickhoff JC, Wuerzberger-Davis SM, Miyamoto S, Thomas CJ, Yang DT#, Capitini CM#, Rui L#. FBXO10 Deficiency and BTK Activation Upregulate BCL2 Expression in Mantle Cell Lymphoma. Oncogene (online, May 9, 2016). (*joint first authors, #joint corresponding authors).
Zheng M, Turton KB, Zhu F, Li Y, Grindle KM, Annis DS, Lu L, Drennan AC, Tweardy DJ, Bharadwaj U, Mosher DF*, Rui L*. A mix of S and ΔS variants of STAT3 enable survival of activated B-cell-like diffuse large B-cell lymphoma cells in culture. Oncogenesis. 2016 Jan 4;4:e184. (joint corresponding authors).
Chiorazzia M*, Rui L*, Yang Y, Ceribelli M, et al (2013). Related F-box proteins control cell death in Caenorhabditis elegans and human lymphoma. Proc Natl Acad Sci USA 110 (10): 3943-3948. (*equal contribution)
Rui L, Schmitz R, Ceribelli M, and Staudt LM (2011). Malignant pirates of the immune system. Nature Immunology 2011; 12 (10): 933-940.
Steidl C, Shah SP, Woolcock BW, Rui L, Kawahara M, et al (2011). MHC class II transactivator CIITA is a recurrent gene fusion partner in lymphoid cancers. Nature. 471 (7338): 377-381.
Rui L, Tolga Emre NC, Kruhlak MJ, Chung HJ, et al (2010). Cooperative epigenetic modulation by cancer amplicon genes. Cancer Cell; 18: 590-605.
Rui L, Vinuesa CG, Blasioli J and Goodnow CC (2003). Resistance to CpG DNA-induced autoimmunity through tolerogenic B cell antigen receptor ERK signaling. Nature Immunology; 4(6): 594-600.
Michael Chiorazzi*, Lixin Rui* Yandan Yang, Michele Ceribelli, et al. Related F-box proteins control cell death in Caenorhabditis elegans and human lymphoma. Proc Natl Acad Sci USA 2013; 110 (10): 3943-3948. (* joint first authors)
Christian Steidl, Sohrab P. Shah, Bruce W. Woolcock, Lixin Rui, Masahiro Kawahara, et al. MHC class II transactivator CIITA is a recurrent gene fusion partner in lymphoid cancers. Nature 2011; 471 (7338): 377-381.
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.
Katharine M. Gosling, Lydia E. Makaroff, Angelo Theodoratos, Yong-Hee Kim, Belinda Whittle, Lixin Rui, Hua Wu, et al. A mutation in a chromosome condensin II subunit, kleisin beta, specifically disrupts T cell development. Proc Natl Acad Sci USA 2007; 104(30): 12445-12450.
Lixin Rui and Christopher C Goodnow. Lymphoma and the control of B cell growth and differentiation (review article). Current Molecular Medicine 2006; 6(3): 291-308
Lixin Rui*, James I Healy*, Julie Blasioli, Christopher C Goodnow. ERK signaling is a molecular switch integrating opposing inputs from B cell receptor and T cell cytokines to control TLR4-driven plasma cell differentiation. The Journal of Immunology 2006; 177(8): 5337-46. (* joint first authors)
Carola G Vinuesa, Matthew C Cook, Constanza Angelucci, Vicki Athanasopoulos, Lixin Rui, Kim M Hill, Di Yu, et al. A RING-type ubiquitin ligase family member required to repress follicular helper T cells and autoimmunity. Nature 2005; 435: 452-8
Lixin Rui, Carrola G Vinuesa, Julie Blasioli and Christopher C Goodnow. Resistance to CpG DNA-induced autoimmunity through tolerogenic B cell antigen receptor ERK signaling. Nature Immunology 2003; 4(6): 594-600