Our research group is primarily interested in the study of respiratory RNA viruses. We have published work on viruses of the families: orthomyxoviridae, paramyxoviridae, and coronaviridae. In particular, our current work is focused on the orthomyxovirus influenza A, as well as the coronavirus SARS-CoV-2, as these are the viruses that have caused, and remain capable of causing, global pandemics.
Influenza viruses are negative sense, RNA viruses that encode their genome across eight genomic segments. Due to the segmented nature of their genome, when a cell is infected with multiple viruses, segment exchange can lead to the generation of new viral variants. These “reassorted” viruses, frequently after reassortment between human and avian/swine strains of influenza, have the ability to cause global pandemics.
Coronaviruses are a family of positive sense, RNA viruses which are known to infect a large range of animals. While there are a number of human coronaviruses, epidemic or pandemic outbreaks are primarily thought to occur when a virus “jumps” from an animal to a human host. The research in our laboratory is currently focused on three major areas of investigation, all with the ultimate goal of developing new therapies that can be used to combat both current and future influenza and coronavirus outbreaks.
Our main research areas are:
1.) Understanding how viral infection induces lung inflammation, and how that inflammation influences recovery from disease.
One of the experimental approaches that the lab frequently takes, is the genetic manipulation of viruses in order to develop new viral-based research tools. These viral tools, together with transgenic animals, have allowed us to ask questions about the biology of viral infections that would have been difficult or impossible to ask with unmodified viruses. In one of our favorite approaches, we have utilized recombinase expressing viruses to label virally infected cells.
This approach has allowed us to understand how pulmonary epithelial cells are changed by viral infection. We have found that many of these changes influence inflammation in the lung, which affects both the severity of viral disease and the time to recovery. Continued work in this area may eventually lead to therapies that help improve recovery rates after viral pneumonia.
2.) Developing biologics and vaccines to prevent viral disease.
Using some of the same viral engineering approaches as above, we have generated viral-based genetic platforms that can be used directly to generate anti-viral biologics or vaccines that avoid some of the problems associated with current vaccines.
For example, by generating viral particles that carry “decoy” genomic segments, we can help prevent viral reassortment and spread. Additionally, one way in which we have been working to improve influenza vaccines is to generate viruses with additional viral antigens incorporated into the virus. Approaches like this may allow us to generate a broader, and ultimately more protective, response to vaccination.
3.) Defining the host proteins that are either required for, or can restrict, viral infection of airway epithelial cells.
Human viruses have dramatically less genetic material relative to their hosts; they therefore rely on co-opting host proteins to complete their replication cycles. Additionally, humans have evolved defensive proteins, that when expressed, are capable of restricting viral infection and/or spread. It isn’t fully understood however, which proteins fall into these categories. Our lab has utilized high throughput screening approaches to define host proteins that fall into both categories.
Our goal is to not only identify these key host proteins, but also develop ways to manipulate them (either decrease expression of required factors or over-express restriction factors) in order to develop new antiviral therapeutics. Further, since many viruses utilize the same host factors, these types of studies may lead to the identification of broadly-acting therapeutics.
Altogether, we take a number of complementary research approaches in order to develop new ways to combat respiratory viral disease. There are many individual projects within these research areas, and we are always looking for new people to join our team. Please get in touch if you are interested in working with us or learning more!