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Wang Lab

Contact Information:
Phone: 303-270-2717 (office), 303-270-2722 (lab)
E-mail: or

Research Interests:
•    Genomic instability and cancer development: Internal or external insults can cause breakages of chromosomes. Incorrect juxtaposition of different pieces of chromosomes during the repair process leads to chromosomal translocation. It is widely accepted that chromosomal translocation can promote cancer development by disrupting tumor suppressors, activating oncogenes, or generating aberrant fusion proteins. Furthermore, cancer type-specific chromosomal translocations are frequently identified in leukemia and lymphomas, and increasingly found in solid tumors. However, many aspects of the mechanisms underlying the generation and cancer-type specificity of chromosomal translocations are poorly understood.  The goal of our laboratory is to understand the molecular mechanisms that promote chromosomal translocations and cancer development in B lymphocytes. Our primary approaches are to establish specific mouse models that resemble human mature B cell lymphomas. In particular, we focus on DNA double strand breaks (DSBs) response factors. These proteins are essential for properly repairing DSBs. In the absence of these factors, DSBs will separate and progress into chromosomal breaks and translocations. We are investigating how these proteins suppress oncogenic translocations. Furthermore, we are elucidating how cancer-type specific translocations are generated at the molecular level, and how mechanistic factors including DSB frequency, spatial proximity of target loci and DNA repair pathways influence translocation frequency and spectrum.
•    Molecular mechanism of somatic hypermutation and class switch recombination: More than 90% of human lymphomas are B cell-derived. This is likely because B cells extensively shuffle their genomic DNA during immune responses. Upon immunizations and infections, activated B cells form a specialized structure termed germinal center (GC). In the GC, two B cell-specific DNA alterations occur, namely somatic hypermutation (SHM) and class switch recombination (CSR). Both SHM and CSR rely on the activity of an enzyme called activation induced deaminase (AID). In activated B lymphocytes, AID causes point mutations in the variable regions of the immunoglobulin (Ig) genes. These mutations cause small changes in the protein sequence of antibodies and lead to increased antibody affinity for specific antigens. AID also induces DSBs in the repetitive switch regions that lie upstream of each constant region exon of the Ig heavy chain locus to mediate CSR.  CSR assigns antigen-appropriate effector functions to antibody molecules and is, therefore, a process important for productive immune responses against pathogens.  Eventually AID-mediated DNA alterations enhance antibody diversity and specificity. Given that AID is a potent DNA mutator, its activity has to be tightly regulated. We are interested in elucidating the molecular mechanisms that regulate AID targeting specificity and efficiency. Furthermore, we are also investigating how AID contributes to genomic instability and cancer development.
•    Metastasis and genomic instability: Tumor cells evolve two distinct features, unlimited growth and metastasis, which are the major causes for cancerous patient mortality. Our interests focus on how tumor cells acquire the ability to metastasize. Metastasis is a complicated process that includes multiple steps of tumor cells detaching from primary lesion, entering, circulating and exiting from blood or lymphatic vessels, and eventually localizing and growing in distal organs. We hypothesize that genomic instability induced by an uncharacterized somatic mutation process in cancer cells may lead to oncogene activation, which in turn endows tumor cells with metastatic potential.  We are interested in identifying the molecular pathways that initiate the mutational process and contribute to tumor cell metastasis. Our current project is to investigate whether aberrant expression of some cell adhesion molecules in certain types of tumor cells is caused by genomic instability.  We are also studying whether and how these cell adhesion molecules function in promoting or suppressing tumor metastasis.

Current Trainees: 

Assistant Research Professor
Zhangguo Chen, Ph.D. Beijing Medical University

Professional Research Assistant
Sawanee Sandy Viboolsittiseri, M.S. Colorado State University

Professional Research Assistant
Maxwell Eder, B.S. University of Denver

Selected Publications:

•    Wang JH (2012). Mechanisms and impacts of chromosomal translocations in cancers. Frontiers of Medicine, 2012;(3):263-74. Epub 2012 Aug 4. PMID: 22865120.
•    Chen Z, Viboolsittiseri SS, O’Connor BP, Wang JH (2012). Target DNA Sequence Directly Regulates the Frequency of AID-Dependent Mutations. Journal of Immunology, [Epub ahead of print]. PMID: 22962683.
•    Wang JH (2012). The role of activation induced deaminase in antibody diversification and genomic instability. Immunologic Research, 2012 [Epub ahead of print]. PMID: 22956489
•    Boboila C, Oksenych V, Gostissa M, Wang JH, Zha S, Zhang Y, Chai H, Lee CS, Jankovic M, Saez LM, Nussenzweig MC, McKinnon PJ, Alt FW, Schwer B (2012). Robust chromosomal DNA repair via alternative end-joining in the absence of X-ray repair cross-complementing protein 1 (XRCC1). Proc. Natl. Acad. Sci. USA, 109(7):2473-8. PMCID: PMC3289296
•    Boboila C, Jankovici M, Yan CT, Wang JH, Wesemann DR, Zhang T, Fazeli A, Feldmane L, Nussenzweig A, Nussenzweig M, Alt FW (2010).  Alternative End-joining Catalyzes Robust IgH Locus Deletions and Translocations in the Combined Absence of Ligase 4 and Ku70. Proc. Natl. Acad. Sci. USA, 107(7):3034-9.
•    Boboila C, Yan C, Wesemann DR, Jankovic M, Wang JH, Manis J, Nussenzweig A, Nussenzweig M, Alt FW (2010).  Alternative End-joining Catalyzes Class Switch Recombination in the Absence of Both Ku70 and DNA Ligase 4. Journal of Experimental Medicine, 207(2):417-27.
•    Wang JH, Gostissa M, Yan CT, Goff P, Hickernell T, Hansen E, Difilippantonio S, Wesemann DR, Zarrin AA, Rajewsky K, Nussenzweig A, Alt FW (2009). Mechanisms Promoting Translocations in Editing and Switching Peripheral B Cells. Nature, 460(7252), 231-6. 
•    Wang JH, Alt FW, Gostissa M, Datta A, Murphy M, Alimzhanov MB, Coakley KM, Rajewsky K, Manis JP, Yan CT (2008).  Oncogenic transformation in the absence of Xrcc4 targets peripheral B cells that have undergone editing and switching. Journal of Experimental Medicine, 205(13), 3079-90. 
•    Chaudhuri J, Basu U, Zarrin A, Yan C, Franco S, Perlot T, Vuong B, Wang J, Phan RT, Datta A, Manis J and Alt FW (2007).  Evolution of the Immunoglobulin Heavy Chain Class Switch Recombination Mechanism. Advances in Immunology, 94, 157-214.
•    Wang J and Fu Y-X (2005).  TNF family members and inflammatory bowel disease. Invited Review. Immunological Review 204, 144-155.
•    Wang Y-G, Kim KD, Wang J, Yu P and Fu Y-X (2005).  Stimulating Lymphotoxin beta Receptor on the Dendritic Cells is Critical for Their Homeostasis and Expansion. Journal of Immunology, 175, 6997–7002.
•    Anders RA, Subudhi SK, Wang J, Pfeffer K, and Fu Y-X (2005). Contribution of the lymphotoxin beta receptor to liver regeneration. Journal of Immunology, 175, 1295–1300.
•    Wang J, Anders R A, Wang Y, Turner J R, Abraham C, Pfeffer K and Fu Y-X (2005).  The Critical Role of LIGHT in Promoting Intestinal Inflammation and Crohn’s Disease. Journal of Immunology, 174, 8173-8182.
•    Wang Y, Subudhi SK, Anders RA, Lo J, Sun Y, Blink S, Wang Y, Wang J, Liu X, Mink K, Degrandi D, Pfeffer K, and Fu Y-X (2005). The Role of Herpes Viral Entry Mediator as a Negative Regulator of T Cell-Mediated Responses. Journal of Clinical Investigation, 115, 711-717.
•    Zarrin AA, Tian M, Wang J, Borjeson T, and Alt FW (2005). Influence of Switch Region Length on Immunoglobulin Class Switch Recombination. Proc. Natl. Acad. Sci. USA, 102(7), 2466-2470.
•    Wang J and Fu Y-X (2004).  The role of LIGHT in T cell-mediated immunity. Immunological Research, 30, 201-214.
•    Wang J, Anders R A, Wu Q, Peng D, Cho J H, Sun Y, Karaliukas R, Kang H S, Turner J R, Fu Y-X (2004). Dysregulated LIGHT expression on T Cells mediates intestinal inflammation and contributes to IgA nephropathy. Journal of Clinical Investigation, 113, 826-835. 
•    Yu P, Lee Y, Liu W, Chin R K, Wang J, Wang Y, Schietinger A, Schreiber H, and Fu Y-X (2004). Priming of naive T cells inside tumors leads to eradication of established tumors. Nature Immunology, 5, 141-149. 
•    Wang J and Fu Y-X. LIGHT-mediated thymocyte selection is dependent on the interaction between TCR and MHC/peptide (2003). Journal of Immunology, 170, 3986-3993.
•    Wang J, Foster A, Chin R, Yu P, Wang Y, Pfeffer K and Fu Y-X (2002). The complementation of lymphotoxin deficiency with LIGHT, a newly discovered TNF family member, for the restoration of secondary lymphoid structure and function. European Journal of Immunology, 32, 1969-79.
•    Wang J, Lo J C, Foster A, Yu P, Chen H M, Wang Y, Tamada K, Chen L, and Fu Y-X (2001). The regulation of T cell homeostasis and autoimmunity by T cell derived LIGHT. Journal of Clinical Investigation, 108, 1771-1780. 
•    Wang J, Chun T, Lo J C, Wu Q, Wang Y, Foster A, Roca K, Chen M, Tamada T, Chen L, Wang C-R, and Fu Y-X (2001). The critical role of LIGHT, a TNF family member, in T cell development. Journal of Immunology 167, 5099-5105.

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