The main focus of the Burk laboratory is to understanding how evolution of human papillomaviruses (HPV) has resulted in the emergence of HPV types that are highly pathogenic and cause multiple cancers in humans (e.g., cervix, head & neck, skin). These investigations extend our collaboration on clinical studies performed by the NCI and others, where we obtain clinical samples to investigate the HPV genome type, variant and methylation status and epidemiological relationship to neoplasia. The papillomaviruses are 8.0 kb double stranded DNA viruses readily amenable to Next-Gen sequencing (NGS), making this system ideal as a model for DNA virus evolution and identification of pathogenic genetic signatures. Over 150 HPV types exist and further characterization of HPVs infecting the population (i.e., from our large sample repository) have allowed us to explore the virus as a species, characterization of the frequency and heterogeneity of HPV types and variants in the population, and the role of viral evolution in pathogenicity. The lab uses phylogenic methods and other analytic strategies to test hypotheses about the relationship and characteristics of HPV genomes and disease. Exploration of natural selection of papillomaviruses has led us to the conclusion that the viruses are evolving through complex means yet to be discovered. The evolutionary studies are also driving experimental studies. We are interested in identifying the activity associated with cancer vs. evolutionary developed phenotypes. Our major collaboration with investigators at the National Cancer Institute, NIH has provided an ideal translational team of world-class epidemiologists, biostatisticians and clinical investigators. In combination with evolutionary biologists at the American Museum of Natural History, our integrative group provides a unique prospective for intellectual growth of students that want to “think outside the box”. More recently, we have studied epigenetic changes to the HPV genome and have startling results on the association of these changes with neoplastic progression. The identification of HPV in specific biological niches has challenged us to explore the microbiome through barcoding and parallel sequencing using NGS methods.
Most recently, we have started asking questions about the complex ecological community of bacteria, fungi, viruses and other organisms and how that might interact for disease outcomes. These studies are built on understanding the application of laboratory tests to population-based studies. They employ NGS and state of the art bioinformatics. Other interests of the lab include the genetics of complex human disease (prostate cancer, excessive sweating) using large case-control clinical collections of genomic DNAs with candidate gene sequencing; and, the cell biology of VHL and its role in primary cilia formation and activity and its disruption in renal cancer.
The lab is dedicated to creating a warm environment based on collaborative science and teamwork. Our mission is to facilitate each individual reaching his or her potential through learning, experimentation and sharing in the pursuit of knowledge to promote human health and development.
Schiffman, M., Rodríguez, A.C., Chen, Z., Wacholder, S., Herrero, R., Hildesheim, A., Desalle, R., Befano, B., Yu, K., Safaeian, M., Sherman, M.E., Morales, J., Guillen, D., Alfaro, M., Hutchinson, M., Solomon, D., Castle, P.E. and Burk, R.D. A population-based prospective study of carcinogenic human papillomavirus variant lineages, viral persistence, and cervical neoplasia. Cancer Res. 70:3159-3169, 2010. PMID: 20354192; PMCID: PMC2855741.
Fu, L., Van Doorslaer, K., Chen, Z., Ristriani, T., Masson, M., Travé, G. and Burk, R.D. Degradation of p53 by human Alphapapillomavirus E6 proteins shows a stronger correlation with phylogeny than oncogenicity. PLoS ONE. 2010;5(9):e12816. Epub 2010 Sept 17. PMID: 20862247; PMCID: PMC2941455.
Castle, P.E., Shaber, R., Lamere, B., Kinney, W., Fetterman, B., Poitras, N., Lorey, T., Schiffman, M., Dunne, A., Ostolaza, J., McKinney, S. and Burk, R. Human papillomavirus (HPV) genotypes in women with cervical precancer and cancer at Kaiser Permanente Northern California. Cancer Epidemiol. Biomarkers Prev. 20:946-953, 2011. PMID: 21415357; PMCID: PMC3117227.
Bottalico, D., Chen, Z., Dunne, A., Ostoloza, A., McKinney, S., Sun, C., Schlecht, N.F., Fatahzadeh, M., Herrero, R., Schiffman, M. and Burk, R.D. The oral cavity contains abundant known and novel human papillomaviruses from the Betapapillomavirus and Gammapapillomavirus genera. J. Inf. Dis. 204:787-792, 2011. PMID: 21844305; PMCID: PMC3156102.
Chen, Z., Schiffman, M., Herrero, R., DeSalle, R., Anastos, K., Segondy, M., Sahasrabuddhe, V., Gravitt, P.E., Hsing, A. and Burk, R.D. Evolution and taxonomic study of HPV16-related Alphapapillomavirus variant genomes: HPV31, HPV33, HPV35, HPV52, HPV58 and HPV67. PLoS ONE. 2011;6(5):e20183. Epub 2011 May 27. PMID: 21673791; PMCID: PMC3103539.
Schiffman, M., Glass, A.G., Wentzensen, N., Rush, B.B., Castle, P.E., Scott, D.R., Buckland, J., Sherman, M.E., Rydzak, G., Kirk, P., Lorincz, A., Wacholder, S. and Burk, R.D. A Long-Term Prospective Study of Type-Specific Human Papillomavirus Infection and Risk of Cervical Neoplasia among 20,000 Women in the Portland Kaiser Cohort Study. Cancer Epidemiol. Biomarkers Prev. 20:3098-1409, 2011. PMID: 21602310; PMCID: PMC3156084.
Smith, B., Chen, Z., Reimers, L., van Doorslaer, K., Schiffman, M., DeSalle, R., Herrero, R., Yu, K., Wang, T. and Burk, R.D. Sequence imputation of HPV16 genomes for genetic association studies. PLoS ONE. 2011;6(6):e21375. Epub 2011 Jun 23. PMID: 21731721; PMCID: PMC3121793.
Mirabello, L., Sun, C., Ghosh, A., Rodríguez, A.C., Schiffman, M., Wentzensen, N., Hildesheim, A., Herrero, R., Wacholder, S., Lorincz, A. and Burk, R.D. Hypermethylation of the HPV16 genome is associated with cervical intraepithelial neoplasia grade 3 in a prospective population-based cohort. J. Natl. Cancer Inst. 104:556-565, 2012. PMID: 22448030; PMCID: PMC3317880.
Wentzensen, N., Sun, C., Ghosh, A., Kinney, W., Mirabello, L., Wacholder, S., Shaber, R., LaMere, B., Clarke, M., Lorincz, A.T., Castle, P.E., Schiffman, M. and Burk, R.D. Methylation of HPV18, HPV31, and HPV45 genomes and cervical intraepithelial neoplasia grade 3. J. Natl. Cancer Inst. 104:1738-49, 2012. PMID: 23093560; PMCID: PMC3571257.
Smith, B.C., McAndrew, T., Chen, Z., Harari, A., Barris, D.M., Viswanathan, S., Rodriguez, A.C., Castle, P., Herrero, R., Schiffman, M. and Burk, R.D. The cervical microbiome over 7 years and a comparison of methodologies for its characterization. PLoS One. 2012;7(7):e40425. Epub 2012 Jul 9. PMID: 22792313; PMCID: PMC3392218.
Van Doorslaer, K. and Burk, R.D. Association between hTERT activation by HPV E6 proteins and oncogenic risk. Virology 433:216-9, 2012. PMID: 22925336; PMCID: PMC3449093.
Clarke, M.A., Wentzensen, N., Mirabello, L., Ghosh, A., Wacholder, S., Harari, A., Lorincz, A., Schiffman, M., and Burk, R.D. Human Papillomavirus DNA Methylation as a Potential Biomarker for Cervical Cancer. Cancer Epidemiol. Biomarkers Prev. 21:2125-37, 2012. PMID: 23035178; PMCID: PMC3664203.
Agalliu, I., Wang, Z., Wang, T., Dunn, A., Parikh, H., Myers, T., Burk, R.D. and Amundadottir. L. Characterization of SNPs associated with prostate cancer in men of ashkenazic descent from the set of GWAS identified SNPs: impact of cancer family history and cumulative SNP risk prediction. PLoS ONE 2013;8(4): e60083. Epub 2013 Apr 3. PMID: 23573233; PMCID: PMC3616024.
Chen, Z., Schiffman, M., Herrero, R., DeSalle, R., Anastos, K., Segondy, M., Sahasrabuddhe, V., Gravitt, P.E., Hsing, A. and Burk, R.D. Evolution and taxonomic classification of Alphapapillomavirus 7 complete genomes: HPV18, HPV39, HPV45, HPV59, HPV68 and HPV70. PLoS ONE. 2013;8(8):e72565. Epub 2013 Aug 16. PMID: 23977318; PMCID: PMC3745470. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0072565
Burk, R.D., Harari, A. and Chen, Z. Human papillomavirus genome variants.
Virology 445:232-243, 2013. PubMed PMID: 23998342; PMCID: PMC3979972.
Full text link: http://www.sciencedirect.com/science/article/pii/S0042682213004388.
Sun, C., McAndrew, T., Smith, B.C., Chen, Z., Frimer, M. and Burk, R.D. Characterization of HPV DNA methylation of contiguous CpG sites by bisulfite treatment and massively parallel sequencing—the FRAGMENT approach.
Front. Genet. 5:150, 2014. doi: 10.3389/fgene.2014.00150.
PubMed PMID: 24917876; PMCID: PMC4042685.
Mirabello, L., Frimer, M., Harari, A., McAndrew, T., Smith, B. Chen, Z., M., Wentzensen, Wacholder, S., Castle, P.E., Raine-Bennett, T., Schiffman, M. and Burk, R.D. HPV16 methyl-haplotypes determined by a novel next-generation sequencing method are associated with cervical precancer. Int. J. Cancer 2014 (in press)
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