University of Pittsburgh Cancer Institute (UPCI)

New Pathogen Discovery (NPD)

MCV GenomeViral cancers provide unique opportunities for cancer treatment and prevention through development of antibody tests, antiviral therapy, and vaccines. At present, only seven established human tumor viruses are known, but numerous human cancers are suspected to have an infectious etiology that has not yet been identified. Discovery of each human tumor virus has spawned a new research field that has contributed to our understanding of infectious tumors and cancer biology.

This research theme, unique to UPCI, leverages UPCI researchers' established expertise in genomic technologies to identify new viral agents contributing to human cancer. NPD activity consists largely of collaborations between computational biologists and genomic research scientists. One recent success was the discovery of the Merkel cell polyomavirus (MCV), which is now known to cause ˜80% of Merkel cell carcinomas.

Selected Publications

  • The 13th human polyomavirus was discovered in an inter-institutional collaboration. New Jersey polyomavirus (NJPyV-2013) was isolated from a pancreatic transplant patient, and is associated with myopathy, blinding retinal vasculitis and necrotizing skin disease. (Mishra et. al., J Infect Dis. 2014 Nov 15;210(10):1595-9.)
  • The microbiome of the upper and lower respiratory tract in healthy HIV-uninfected nonsmokers and smokers was compared in a multicenter cohort. This study was the largest to examine composition of the lower respiratory tract microbiome in healthy individuals and the first to use the neutral model to compare the lung to the mouth. Specific bacteria appear in significantly higher abundance in the lungs than would be expected if they originated from the mouth, demonstrating that the lung microbiome does not derive entirely from the mouth. The mouth microbiome differs in nonsmokers and smokers, but lung communities were not significantly altered by smoking. (Morris et. al., Am J Respir Crit Care Med. 2013 May 15;187(10):1067-75.)
  • Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) are related human tumor viruses that cause primary effusion lymphomas (PEL) and Burkitt's lymphomas (BL), respectively. To evaluate the expression of viral genes, high-resolution separation and mass spectrometry coupled with custom tiling arrays was utilized to align the viral proteomes and transcriptomes of three PEL and two BL cell lines under latent and lytic culture conditions. The majority of viral genes were efficiently detected at the transcript and/or protein level on manipulating the viral life cycle. Overall the correlation of expressed viral proteins and transcripts was highly complementary in both validating and providing orthogonal data with latent/lytic viral gene expression. Our approach also identified novel viral genes in both KSHV and EBV, and extends viral genome annotation. Several previously uncharacterized genes were validated at both transcript and protein levels. This systems biology approach coupling proteome and transcriptome measurements provides a comprehensive view of viral gene expression that could not have been attained using each methodology independently. (Dresang et. al., BMC Genomics. 2011 Dec 20;12:625.)

Members

Section Leader: Yuan Chang, MD

Chang, Yuan, MD
Pathology
Pipas, James, PhD
Biological Sciences
Moore, Patrick, MD, MPH
Microbiology and Molecular Genetics