When Eva Gottwein, PhD, assistant professor of Microbiology-Immunology, was searching for a postdoctoral position, microRNAs, tiny bits of genetic material, began to emerge as a large class of regulatory RNAs and the first viral microRNAs were discovered. Interested in this field, Gottwein began a new line of work in the lab of Bryan Cullen, PhD, at Duke University studying microRNAs encoded by Kaposi’s Sarcoma-associated Herpesvirus (KSHV).
“When I began this work, not a single target of the KSHV microRNAs was known,” said Gottwein. “At the conclusion of my postdoctoral work, we had identified thousands of viral microRNA binding sites at nucleotide resolution, which allowed me to initiate the functional work that we are pursuing now.”
What are your research interests?
My broad research interest is on how viruses manipulate the cellular environment to their advantage. We focus on how virally encoded microRNAs alter cellular gene expression. We have shown that the microRNAs encoded by the oncogenic human herpesvirus KSHV likely regulate hundreds of human messenger RNAs, by binding to thousands of sites in the human transcriptome. Our current projects take advantage of this information to identify and understand roles these microRNAs play in viral oncogenesis.
A secondary interest is to use virally encoded microRNAs as models to study the fundamental rules of target recognition by microRNAs. I enjoy the inherently multidisciplinary nature of our work, which touches on virology, genomics, molecular biology, cancer biology, and cell biology.
What is the ultimate goal of your research?
Over the next few years, we hope to gain a detailed understanding of the KSHV microRNA targetome, i.e. to identify the messenger RNAs regulated by these viral microRNAs in the different cell types this virus infects. We plan to use this information to achieve a basic understanding of the most important functions of the KSHV microRNAs. Our data suggest that there are several unexpected cellular processes these viral microRNAs interfere with and we hope that our current work will open up new frontiers in the study of virus-host interactions and viral oncogenesis.
How does your research advance medical science and knowledge?
As the causative agent of Kaposi’s Sarcoma and B cell lymphomas, KSHV remains an important human pathogen, and our work contributes to a better understanding of KSHV pathogenesis. Gaining knowledge of the basic mechanisms of microRNA target recognition is essential for the study of the rapidly emerging roles of cellular or viral microRNAs in many different diseases, including cancer.
How is your research funded?
My lab is funded by a grant from the American Cancer Society, Illinois Division, and by an R01 grant from the National Cancer Institute (NCI). In the NCI-funded work, we study how and why some viral microRNAs mimic the function of cellular microRNAs.
Who makes up your research team?
I work with two postdocs, Mark Manzano, PhD, and Eleonora Forte, PhD. When I have time, I still do experiments myself. Mark and Eleonora pursue both independent and collaborative projects. I’m involved in all projects and enjoy establishing new techniques and projects in the lab.
What types of collaborations are you engaged in across campus (and beyond)?
We have benefitted in many ways from the collaborative atmosphere at Feinberg and have had help from several labs who have shared reagents or expertise. For example, the lab of Greg Smith, PhD, associate professor of Microbiology-Immunology, helped us to establish bacmid recombineering technology in our lab. We are also working with the Next Generation Sequencing Core at Northwestern University. Outside of Feinberg, we have collaborated with Dr. Nikolaus Rajewsky’s lab at the Max Delbrück Center for Molecular Medicine in Berlin, Germany, on work that uses the KSHV microRNAs as tools to better understand microRNA target recognition.