A.B., 1967, Organic Chemistry, Harvard University
M.S., 1968, Physical Chemistry, Columbia University
Ph.D., 1973, Molecular Biology, Columbia University
Postdoctoral research: Karolinska Institute, Stockholm, Sweden
We work with Epstein-Barr Virus (EBV) because it causes several different cancers in people. EBV is a herpesvirus that causes the common, benign infectious mononucleosis, as well as lymphomas such as Burkitt's Lymphoma, most B-cell lymphomas in immunocompromised hosts, and carcinomas such as nasopharyngeal carcinoma. We study EBV both to understand its contributions to these diseases molecularly and to develop rational means to treat them.
Our research focuses on two facets of EBV pivotal to its inducing and maintaining human tumors. One gene product of EBV, LMP1, mimics cellular signaling pathways but in a ligand-independent manner. Its signaling drives proliferation of EBV-infected B-cells, but at high levels inhibits that proliferation. We are dissecting the mechanisms by which LMP1 regulates its host cell both positively and negatively. A second gene product of EBV, EBNA1, binds several elements of EBV's origin of plasmid synthesis, oriP, to mediate the synthesis and maintenance of the viral replicon in proliferating cells. EBV's replicon replicates once per S-phase and uses the cell's DNA synthetic machinery to do so. We study EBNA1 and oriP to elucidate the mechanisms by which EBV DNA is synthesized and segregated to daughter cells. We also study this viral replicon to gain insights into how EBV subverts its host's synthetic machinery to support extrachromosomal DNA synthesis. Finally we are studying EBNA1 which not only mediates replication of EBV's replicon, but also inhibits apoptosis in infectious B-cells to understand its roles in supporting survival of EBV-associated tumors. We want to target EBNA1's survival functions to develop treatments for tumors caused by EBV.
Lab website: http://mcardle.oncology.wisc.edu/sugden
Chakravorty A, Sugden B. Long-distance communication: Looping of human papillomavirus genomes regulates expression of viral oncogenes. PLoS Biol. 2018 Nov 27;16(11):e3000062. doi: 10.1371/journal.pbio.3000062. [Epub ahead of print] PubMed PMID: 30481166.
Chiu YF, Sugden B. Plasmid Partitioning by Human Tumor Viruses. J Virol. 2018 Apr 13;92(9). pii: e02170-17. doi: 10.1128/JVI.02170-17. Print 2018 May 1. Review. PubMed PMID: 29467315; PubMed Central PMCID: PMC5899212
Chiu YF, Sugden AU, Fox K, Hayes M, Sugden B. Kaposi's sarcoma-associated herpesvirus stably clusters its genomes across generations to maintain itself extrachromosomally. J Cell Biol. 2017 Sep 4;216(9):2745-2758. doi: 10.1083/jcb.201702013. Epub 2017 Jul 10. PubMed PMID: 28696226; PubMed Central PMCID: PMC5584176. [Erratum published in J Cell Biol. 2018 Aug 22.]
Yang YC, Liem A, Lambert PF, Sugden B. Dissecting the regulation of EBV's BART miRNAs in carcinomas. Virology. 2017 Mar 1;505:148-154. doi: 10.1016/j.virol.2017.02.013. PubMed PMID: 28259048; PubMed Central PMCID: PMC5504693.
Albanese M, Tagawa T, Bouvet M, Maliqi L, Lutter D, Hoser J, Hastreiter M, Hayes M, Sugden B, Martin L, Moosmann A, Hammerschmidt W. Epstein-Barr virus microRNAs reduce immune surveillance by virus-specific CD8+ T cells. Proc Natl Acad Sci U S A. 2016 Oct 18;113(42):E6467-E6475. PubMed PMID: 27698133.; PubMed Central PMCID: PMC5081573.
Chiu YF, Sugden B. Epstein-Barr Virus: The Path from Latent to Productive Infection. Annu Rev Virol. 2016 Sep 29;3(1):359-372. PubMed PMID: 27578440.
Lee D, Norby K, Hayes M, Chiu YF, Sugden B, Lambert PF. Using Organotypic Epithelial Tissue Culture to Study the Human Papillomavirus Life Cycle. Curr Protoc Microbiol. 2016 May 6;41:14B.8.1-14B.8.19. doi: 10.1002/cpmc.4. PubMed PMID: 27153383; PubMed Central PMCID: PMC5035105.
Tagawa T, Albanese M, Bouvet M, Moosmann A, Mautner J, Heissmeyer V, Zielinski C, Lutter D, Hoser J, Hastreiter M, Hayes M, Sugden B, Hammerschmidt W. Epstein-Barr viral miRNAs inhibit antiviral CD4+ T cell responses targeting IL-12 and peptide processing. J Exp Med. 2016 Sep 19;213(10):2065-80. doi: 10.1084/jem.20160248. Epub 2016 Sep 12. PubMed PMID: 27621419; PubMed Central PMCID: PMC5030804.
Chakravorty A, Sugden B. The AT-hook DNA binding ability of the Epstein Barr virus EBNA1 protein is necessary for the maintenance of viral genomes in latently infected cells. Virology. 2015 Oct;484:251-8. doi: 10.1016/j.virol.2015.05.018. Epub 2015 Jun 27. PubMed PMID: 26122471; PubMed Central PMCID: PMC4567472.
Kuzembayeva, M., Hayes, M., and Sugden, B. Multiple Functions Are Mediated by the miRNAs of Epstein-Barr Virus. Curr. Opin. Virol., 7C: 61-65, 2014.
Shrestha, P., and Sugden, B. Identification of Properties of the Kaposi’s Sarcoma-Associated Herpesvirus Latent Origin of Replication That Are Essential for the Efficient Establishment and Maintenance of Intact Plasmids. J. Virol., 88(15): 8490-8503, 2014.
Sugden, B. Epstein-Barr Virus: The Path from Association to Causality for a Ubiquitous Human Pathogen. PLoS Biol., 12(9): e1001939, 2014.
Vereide, D. T., Seto, E., Chiu, Y.-F., Hayes, M., Tagawa, T., Grundhoff, A., Hammerschmidt, W., and Sugden, B. Epstein-Barr Virus Maintains Lymphomas Via Its miRNAs. Oncogene, 33(10): 1258-1264, 2014.
Chiu, Y.-F., Sugden, A. U., and Sugden, B. Epstein-Barr Viral Productive Amplification Reprograms Nuclear Architecture, DNA Replication, and Histone Deposition. Cell Host Microbe, 14(6): 607-618, 2013.
Hammerschmidt, W., and Sugden, B. Replication of Epstein-Barr Viral DNA. Cold Spring Harb. Perspect. Biol., 5(1): pii: a013029, 2013.
Westhoff Smith, D., and Sugden, B. Potential Cellular Functions of Epstein-Barr Nuclear Antigen 1 (EBNA1) of Epstein-Barr Virus. Viruses, 5(1): 226-240, 2013.
Chiu, Y.-F., Sugden, B., Chang, P.-J., Chen, L.-W., Lin, Y.-J., Lan, Y.-C., Lai, C.-H., Liou, J.-Y., Liu, S.-T., and Hung, C.-H. Characterization and Intracellular Trafficking of Epstein-Barr Virus BBLF1, a Protein Involved in Virion Maturation. J. Virol., 86: 9647-9655, 2012.
Kuzembayeva, M., Chiu, Y.-F., and Sugden, B. Comparing Proteomics and RISC Immunoprecipitations to Identify Targets of Epstein-Barr Viral miRNAs. PLoS One, 7(10):e47409, 2012.
Norby, K., Chiu, Y.-F., and Sugden, B. Monitoring Plasmid Replication in Live Mammalian Cells over Multiple Generations by Fluorescence Microscopy. J. Vis. Exp., (70):e4305, 2012.
Pratt, Z. L., and Sugden, B. How Human Tumor Viruses Make Use of Autophagy. Cells, 1: 617-630, 2012.
Pratt, Z. L., Zhang, J., and Sugden, B. The Latent Membrane Protein 1 (LMP1) Oncogene of Epstein-Barr Virus Can Simultaneously Induce and Inhibit Apoptosis in B Cells. J. Virol., 86: 4380-4393, 2012.