Silvi Rouskin

Silvi Rouskin

Assistant Professor of Microbiology
Harvard Medical School
Silvi Rouskin headshot.

My area of expertise is investigating the how RNA structure and function impacts viral infections and human disease. I immigrated by myself to the United States from Bulgaria to pursue a career in science. At sixteen, I became a freshman at Florida Institute of Technology, where I obtained a BS in physics while doing undergraduate research in biology. I then worked as a research assistant in the lab of Dr. Joseph DeRisi and stayed at UCSF to obtain my PhD in molecular biology and biochemistry the lab of Jonathan Weissman. In my graduate work, I pioneered an approach termed dimethyl sulfate-sequencing (DMS-seq) to study RNA folding in vivo at single nucleotide resolution across the entire transcriptome. Previous methods had only examined how RNA folds inside a test tube one RNA sequence at a time. Using DMS-seq, I identified large differences in the folding of RNAs depending on the physiological environment and uncovered new regulatory elements in bacteria and yeast. In lieu of a traditional postdoctoral fellowship, I started my own research group as a Fellow at the Whitehead Institute for Biomedical Research, expanding my research to study human immunodeficiency virus 1 (HIV-1) and SARS-CoV-2.

To overcome fundamental limitations in the RNA structure field, my lab developed single-molecule chemical probing (Zubradt et.al., Nature Methods, 2016) and the mathematical and computational tools needed to distinguish multiple RNA conformations formed by the same sequence (Tomezsko et.al, Nature 2020). We discovered alternative RNA structures that dictate splicing decisions to control gene expression of HIV-1. With the onset of the pandemic, my lab determined the complete genomic RNA structure of SARS-CoV-2 in infected cells and discovered alternative conformations at a frameshifting element, which is critical for the production of the SARS-CoV-2 replicase.

My achievements were recognized with several prestigious awards including the 2021 Vilcek Prize for Creative Promise in Biomedical Science, the Burroughs Wellcome Fund, the Smith Family Award, and the 2015 Harold M. Weintraub Graduate Student Award.

The current research in my lab focuses on defining the molecular mechanisms driving critical steps in the life cycle of RNA viruses such as transcription, translation, and replication, as well as the host response to viral infection. My long-term goal is to understand, predict, and control condition-specific RNA processing choices that define both pathogen and host responses during infection. By combining multiple areas of cross disciplinary research, my ultimate goal is to derive basic principles for gene control and develop a novel class of therapeutics based on stabilizing or disrupting RNA structures.