Products & Services
Applications

Applications

Nanopore sequencing offers advantages in all areas of research. Our offering includes DNA sequencing, as well as RNA and gene expression analysis and future technology for analysing proteins.

Learn about applications
View all Applications
Resources
News Explore
Careers Contact

Christopher Oakes

Discerning the origin of Epstein-Barr virus in patients using nanopore-derived DNA methylation signatures

About Christopher Oakes

Christopher Oakes is an Assistant Professor in the Departments of Internal Medicine/Division of Hematology and Biomedical Informatics at The Ohio State University. He performed his graduate studies at McGill University in Canada and post-doctoral studies at the German Cancer Research Center in Heidelberg, Germany. His laboratory investigates epigenomic, genetic and other molecular features of a broad range of hematological malignancies, with a focus on chronic lymphocytic leukemia and other non-Hodgkin’s lymphomas and acute myeloid leukemia. He explores high-throughput epigenetic and molecular profiling data and combines these analyses with functional evaluation of key genes and molecular pathways. His laboratory is interested in the developmental origins of epigenetic programs in lymphoid and myeloid malignancies and aim to uncover the ontogeny of disease development. Current research focuses on investigating the role that perturbation of gene function plays in establishing aberrant global epigenetic states and landscapes. Beyond fundamental tumor biology, he aims to develop novel molecular diagnostics clinical for diagnosis, stratification and prediction of treatment responses, as well as the identification of novel therapeutic targets.

Abstract

Epstein-Barr virus (EBV) infects the vast majority of the human population. In rare instances EBV is involved in the generation of lymphomas and other malignancies. The presence of elevated EBV levels in blood is currently used in the clinical diagnosis and subclassification of infectious disease and lymphoma; yet when patients present with detectible EBV in blood, it is uncertain if this represents an active infection or an evolving malignancy. Epigenetic changes occur as an essential component of the EBV life cycle, controlling the virus’s ability to infect, establish a chronic (latent) infected population of cells, and later reactivate to produce infectious virions. We have found that tumor-derived EBV DNA displays specific DNA methylation signatures and EBV virion-derived infectious particles or lytically-active (virus-replicating) cells contain largely unmethylated EBV DNA. Importantly, tumor-specific EBV methylation patterns are maintained in circulating plasma (cell-free) DNA. We have employed nanopore sequencing to interpret EBV DNA methylation signatures in patients. Analysis of tumor and plasma-derived EBV methylomes from lymphoma patients and donors with infectious EBV revealed highly discernable DNA methylation signatures, with higher levels of methylation in primary EBV+ lymphoma cases. In addition, we have uncovered an unexpectedly high complexity of EBV methylation patterns among tumors and evidence that epigenetic differences correlate with viral gene expression. These data may predict responses to combined antiviral and immunotherapeutic strategies in cancer patients. In summary, our work aims to develop approaches that harness a patient’s EBV epigenetic signature with the aid of nanopore sequencing to rapidly discern benign versus cancerous clinical scenarios and help direct the use of current and novel therapies.

Christopher Oakes

Christopher Oakes

Back
Open a chat to talk to our sales team