Steven Baker, PhD

Influenza A viruses are continually re-emerging respiratory viruses that burden health care systems due to yearly epidemics and occasional pandemics. Although there are current antiviral therapies and vaccines used to treat or prevent infection, a better understanding of how the virus interacts with cellular factors is needed to develop new and more effective treatment and prevention. Upon lung cell infection, influenza viruses trigger fluctuations in the levels of gene expression (the process by which the information encoded in a gene is turned into a function) of many genes in airway cells. Some of these genes are expressed to thwart viral infection, but some have been co-opted by viruses to be beneficial. One way the expression of genes is changed is through the process called alternative mRNA splicing, whereby a single gene can be expressed as multiple variants with distinct functions. We will use new technology to learn how genes are spliced during infection, and will uncover pro-viral and anti-viral genes unleashed by alternative splicing. Understanding this process will establish a new front in the battle against influenza virus and other respiratory pathogens.

Update:

In our first year of research, we made significant advancements in understanding how cells respond to respiratory viruses at a genetic level. First, we developed a computational method to identify numerous modified gene products resulting from alternative splicing during immune activation. Ongoing research aims to quantify and categorize these alternatively spliced products in response to respiratory virus infection. Secondly, we explored the role of one of these novel modified products in depth; this product derives from a gene well-known for its role in immune defense against viruses. Our experiments confirmed that this novel product is made during immune responses and it further appears to be more effective in antagonizing influenza virus than the original well-characterized form. Our findings pave the way for future treatments aimed at preventing or treating lung diseases caused by inflammation.