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.
