Bill Sugden, Ph.D.
James A. Miller
Professor of Oncology
American Cancer Society Research Professor
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
Office: 814 McArdle
Laboratory
Telephone: Office - (608) 262-1116; Lab -
(608) 262-6697
Email: sugden@oncology.wisc.edu
Lab Home
Page
Research Interests: Molecular biology of the human tumor virus, Epstein-Barr virus
Research Description: 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.Selected recent publications
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.
Dresang, L. R., Teuton, J. R., Feng, H., Jacobs, J. M., Camp, D. G. II, Purvine, S. O., Gritsenko, M. A., Li, Z., Smith, R. D., Sugden, B., Moore, P. S., and Chang, Y. Coupled Transcriptome and Proteome Analysis of Human Lymphotrophic Tumor Viruses: Insights on the Detection and Discovery of Viral Genes. BMC Genomics, 12(1):625, 2011.
Vereide, D. T., and Sugden, B. Lymphomas Differ in Their Dependence on Epstein-Barr Virus. Blood, 117: 1977-1985, 2011.
Dar, W. A., and Sugden, B. Epstein-Barr Virus as a Pathogen. In: K. Khalili and K.-T. Jeang (Eds.), Viral Oncology: Basic Science and Clinical Applications, Chapter 21, pp. 425-452. New Jersey: Wiley-Blackwell, 2010.
Vereide, D., and Sugden, B. Insights into the Evolution of Lymphomas Induced by Epstein-Barr Virus. Adv. Cancer Res., 108: 1-19, 2010.
Dresang, L. R., Vereide, D. T., and Sugden, B. Identifying Sites Bound by Epstein-Barr Virus Nuclear Antigen 1 (EBNA1) in the Human Genome: Defining a Position-Weighted Matrix To Predict Sites Bound by EBNA1 in Viral Genomes. J. Virol., 83: 2930-2940, 2009.
Lee, D. Y., Lee, J., and Sugden, B. The Unfolded Protein Response and Autophagy: Herpesviruses Rule! J. Virol., 83: 1168-1172, 2009.
Pratt, Z. L., Kuzembayeva, M., Sengupta, S., and Sugden, B. The microRNAs of Epstein-Barr Virus Are Expressed at Dramatically Differing Levels Among Cell Lines. Virology, 386: 387-397, 2009.
Vereide, D., and Sugden, B. Proof for EBV’s Sustaining Role in Burkitt’s Lymphomas. Semin. Cancer Biol., 19: 389-393, 2009.
Lambert, P. F., and Sugden, B. Viruses and Human Cancer, Chapter 11, pp. 153-169. In: M. D. Abeloff, J. O. Armitage, J. E. Niederhuber, M. B. Kastan, and W. G. McKenna (Eds.), Abeloff’s Clinical Oncology, Fourth Edition, 2555 pp. Philadelphia: Churchill Livingstone, imprint of Elsevier, 2008.