Gehrke Laboratory

The Gehrke laboratory studies RNA viruses that cause hemorrhagic fevers. Hemorrhagic fever viruses use RNA (ribonucleic acid) instead of DNA (deoxyribonucleic acid) as their genetic material. Familiar examples such as Dengue, Ebola, Marburg, and Lassa are significant world health challenges as well as potential bioterror threats.

We are a basic science laboratory. We want to understand how viruses can be elegant self-promoters, finding clever ways to hide from the host immune system and favor their own replication. By studying RNA viruses, we can learn a great deal about normal host physiology. Indeed, many fundamental discoveries in cellular and molecular biology have been made while studying viruses. And as we learn more about the basic science of viruses and their interactions with their hosts, we aim to translate discoveries into therapeutics and diagnostic devices.

The analysis of RNA-protein interactions is a Gehrke laboratory staple. We are interested in how viral (see Guogas ’04). and host (see Gomila ’11) proteins bind to viral RNAs to change their structures and regulate their functions. As a current project, we are interested in how viral RNAs, including dengue, can be translated efficiently by ribosomes while lacking a fundamental structural feature of cellular messenger RNAs: the poly(A) tail (translation without polyadenylation).

How does a cell “know” that it has been invaded by a virus, and how does the cell distinguish its own RNAs (“self”) from the foreign invader’s (“non-self”)? The answers to these questions direct us to study the activation of the innate immune signaling by viral RNAs (innate immunity).

Colleagues in virus-endemic areas of the world remind us that the lack of rapid point-of-care diagnostics to detect and identify viral infections is a significant problem. Although dengue affects many tropical areas of the world, the continental United States is not immune: Florida experienced a dengue epidemic in 2010. Dengue virus exists in four different forms, or serotypes. The appearance of a new serotype can trigger an epidemic; therefore, we are collaborating engineers to develop and test a rapid point-of-care lateral flow rapid diagnostic that will distinguish the four serotypes and serve as an early warning tool (diagnostic device).

High throughput screening has become commonplace, with many groups screening entire genomes to identify key regulatory genes that might be targets for small molecule inhibitors. We hypothesize that a virus’ replication efficiency is tissue-specific, meaning that a cocktail of inhibitors, each with tissue specificity, might have enhanced therapeutic value. The approach is less focused on whole genome screening, and more focused on smaller scale functional screening to identify host genes and regulatory pathways that are required for efficient virus replication. (screening for viral dependency factors).