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.
Honors & Awards
- 2014- UW ICTR KL2 Scholar Award
- 2013 – Editorial Board, Journal of Hematology and Transfusion
- 2006-2007 – CJ Martin Postdoctoral Fellowship from NHMRC of Australia
- 2013 – American Society of Hematology
- 2010 – American Association for Cancer Research
Speeches and Presentations
- The F-box protein FBXO10 functions as a tumor suppressor. McArdle Seminar in Cancer Biology, University of Wisconsin-Madison, January 30, 2013 (invited speech).
- Frontiers in Basic Immunology 2012, NIH, Bethesda, MD, October 4-5, 2012.
- JAK cooperates with JMJD2C to modulate epigenome of lymphoid cancers. The JAK-STAT pathway (20 years from discovery to drugs). September 22-24, 2011, NIH, Bethesda, MD, USA (poster).
- DRE-1/FBXO11 promotes apoptosis and behaves as a human tumor suppressor. Keystone Symposia – B cells: new insights into normal versus dysregulated function. April 12-17, 2011, Whistler, British Columbia, Canada (poster).
- FBXO11 mutations in diffuse large B-cell lymphoma. LLMPP Investigators Meeting, July 8-9, 2011, Bethesda, Maryland, USA (invited speech).
- Annual Meeting of American Association for Cancer Research. April 17-21, 2010, Washington DC, USA.
- An RNA interference screen reveals multi-functions of chromosome 9p24 amplicon in PMBL and Hodgkin’s lymphoma. The 2009 NIH Immunology Retreat, September 23-25, 2009, Gettysburg, PA, USA (invited speech).
- BACR, EACR conference: Chromatin and Cancer; Transcription and Cancer, July 6-10, 2009, Churchill College, Cambridge, UK.
- Functional analysis of 9p24 gene amplification in PMBL and Hodgkin’s lymphoma. The 2008 NIH Immunology Retreat, October 1-3, 2008, Gettysburg, PA, USA (poster).
- Joint Metastasis Research Society-AACR Conference on Metastasis, August 3-7, 2008, Vancouver, Canada.
- Functional genomics in PMBL and Hodgkin’s lymphoma. LLMPP Investigators Meeting, July 23-24, 2008, Bethesda, Maryland, USA (invited speech).
- Kreg Grindle, Senior Research Specialist, Lab Manager
- Amanda Drennan, Postdoctoral Research Associate
- Yangguang (Sunny) Li, Postdoctoral Research Associate
- Fen Zhu, Graduate Student (CMP program)
- Jared Wolff, Undergraduate Student
- Nicholas Pflum, Undergraduate Student
- Paul Jobin, Undergraduate Student
- 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.
- 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.