What we do in the lab…

Tobacco Mosaic Virus–the first virus to be crystallized. Image by Jean-Yves Sgro, U. Wisconsin.

The Gehrke laboratory studies RNA viruses that use RNA (ribonucleic acid) instead of DNA (deoxyribonucleic acid) as their genetic material. RNA viruses cause many serious human diseases and include Dengue, Zika, Chikungunya, Ebola, Marburg, and Lassa.  Some are also 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 or thwart the host immune system while favoring 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. New virus threats will continue to emerge to threaten human health, and our goals include attempting to prepare  by designing rapid diagnostics for surveillance and clinical detection.

A current focus on the laboratory is on developing two-dimensional and three-dimensional tissue models of infectious diseases.  With funding from the National Institutes of Health, we have formed a three-laboratory consortium, MIT-HTMID, that includes the Jaenisch and Sabatini laboratories at the Whitehead Institute. With a focus on induced pluripotent stem cells (iPS cell)- and embryonic stem cell (ES cell)-derived neuronal cells, the group seeks to understand how neurotropic viruses (West Nile, Zika, Japanese Encephalitis, Powassan) infect cells to cause significant pathologies, including microcephaly and encephalitis.

Quantifying gene expression changes that accompany virus infection generates datasets that, when deciphered, open windows to explain viral pathogenesis.  The Gehrke lab is using primary iPS- and ES-derived cells, in collaboration with the Jaenisch lab, to define the cell types that are susceptible to virus infection, leading to pathogenesis. For gene expression, we study changes in chromatin accessibility (epinomics), changes in RNA transcription, and changes in RNA translation that accompany virus infection. The goal is to decipher patterns of gene expression that lead to severe defects such as Zika virus-mediated microcephaly.

Rapid diagnostics are needed both for epidemiological surveillance and for use as point of care devices to detect clinical virus infections. We have developed rapid antigen-based diagnostics that detect and distinguish the four dengue virus serotypes (DENV1-4) as well as Zika virus infections, without detectable cross reactivity, in patient sera. The technology is a platform approach that can be applied to detect emerging viruses. By screening monoclonal antibody libraries against panels of proteins from different viruses, it is possible to identify monoclonal antibodies that recognize common and unique viral protein epitopes (regions of viral proteins that antibodies recognize).  These monoclonal antibody pairs are the foundation of our rapid antigen diagnostics. Additional efforts are underway to develop specific serological tests to detect immunoglobulins (IgG/IgM/IgA) that are also important markers of virus infection, and whose identification can improve the course of patient care.