Our research group is interested in understanding how damage to the lung occurs, is detected, and how the organ eventually returns to homeostasis. The respiratory tract is constantly exposed to insults, both environmental (i.e. air pollution) and infectious (i.e. viruses and bacteria), and improper responses to these insults is a significant source of acute and chronic disease. Our research studies are designed to understand how the lung senses damage as well as the repair pathways that are activated after the insult is eliminated. By studying these processes in systems where the responses are either appropriate or inappropriate, we hope to identify points of intervention for future therapeutic development.
Specific areas of currently funded research are described in more detail below.
Research Area (1) – Understanding how viral infection induces lung inflammation, and how that inflammation influences recovery from disease.
We have previously demonstrated that some previously infected pulmonary epithelial cells persist in the host for extended periods following viral infection, and these cells undergo significant changes as a result of having been infected. Many of these changes contribute to the inflammatory state of the lung, which in turn affects both the severity of the viral disease and the time required for recovery. The persistence of viral-induced changes in these epithelial cells suggests that they may play a crucial role in the pathophysiology of viral pneumonia. Our current studies aim to gain a deeper understanding of the specific mechanisms driving these alterations, which could ultimately pave the way for the development of targeted therapies to mitigate the long-term impacts on lung function and inflammation. Ultimately, such therapies could lead to improved recovery outcomes for patients suffering from viral pneumonia, potentially reducing both the duration and severity of illness.
Research Area (2) – Understanding how the innate immune response is activated and controlled in the lung.
The lungs detect damage and infection through a complex network of immune and sensory mechanisms. Epithelial cells lining the airways act as the first line of defense, equipped with pattern recognition receptors such as Toll-like receptors (that identify harmful pathogens or environmental irritants. When these receptors detect danger, they trigger inflammatory responses by releasing cytokines and chemokines, which recruit immune cells like macrophages and neutrophils to clear the threat. Understanding these processes is crucial for developing future therapeutics, as targeting specific signaling pathways could help modulate excessive inflammation seen in conditions like chronic obstructive pulmonary disease or acute respiratory distress syndrome. By developing ways to fine-tune immune responses, we hope to ultimately improve outcomes for respiratory diseases.
Research Area (3) – Developing safe and durable vaccines to prevent influenza viral disease.
Influenza viruses naturally undergo frequent mutation and genetic reassortment, leading to new strains that can evade immune defenses and cause widespread outbreaks or pandemics. A universal vaccine would theoretically target conserved regions of the virus, providing broad and long-lasting protection against multiple independent strains. Our group is actively working on new vaccine formulations that help direct the immune responses away from antigenically variable domains toward these more conserved epitopes. The development of a truly universal influenza vaccine has the potential to revolutionize public health by eliminating the need for annual vaccines by providing stable, long-term immunity against what is currently constantly evolving viral threat.
Research Area (4) – 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 antiviral therapeutics.
In sum, we take a number of complementary research approaches in order to better understand, and develop new ways to, respiratory 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!
