We are interested in understanding how one lung disease affects the response to a secondary insult in ether the lung or in a distal part of the body. Using clinically relevant model systems we examine the impact of the lung microbiome on pulmonary diseases, alterations of the immune response during pulmonary viral/bacterial coinfection, and the lung epithelial/endothelial responses during lung infection, damage, and disease. The overall goal of our research is to develop improved therapeutics for complex lung diseases.
1) Host resilience to infection:
Pneumonia is the leading cause of death from infection of children under five. It is higher than deaths caused by HIV, Malaria, or even diarrheal diseases (UNICEF/WHO, 2006, Pneumonia: The Forgotten Killer of Children). Influenza virus is a leading cause of viral pneumonia, and a common clinically relevant complication of influenza virus infection is bacterial pneumonia. We have developed a model for influenza virus/bacterial coinfection in which we can study host resilience as opposed to pathogen clearance. With this in vivo model we discovered that tissue repair is an important factor in making a host more tolerant to infection. We have also investigated the role that programmed cell death plays in host resilience. Currently we are using transcriptional profiling to determine novel host resilience pathways.
2) Airway microbiome
Another research interest of the lab is to understand changes that occur in the airway microbiome during lung diseases. The field of the airway microbiome is an emerging field, and as such we have had to develop several new techniques, and adapt techniques used for other microbiomes to this unique space. In particular we are interested in the microbiome of the lung tissue. We aim to the composition of the airway during health and disease, and how changes in composition impact the overall health of the host.
3) E-cigarette vapor toxicity on the lung epithelium and pulmonary immune responses.
Electronic cigarettes represent a modified risk nicotine delivery system designed as an alternative to conventional cigarettes. In recent years, e-cigarettes have steadily increased their share of the market, outpacing the scientific community’s understanding of their potential harmful effects. These products function by aerosolizing e-liquid comprised of polyethylene glycol, glycerol, nicotine, and flavorings. Toxicity of these ingredients is not well understood and, in many cases, identity of flavoring compounds is unknown. In order to investigate the health impact of e-cigarettes, we determined toxic effects of e-cigarette vapor on cells of the lung. We are studying the impact of this vapor on both the pulmonary immune response and the resilience response.
4) Immune Triage: Understanding Host resilience to Infection and Trauma
The development of pneumonia in trauma and post-surgical patients leads to increased morbidity and mortality. Lung infections occur for diverse reasons in a hospital setting, but the impact that pneumonia onset has on wound healing responses has not been examined. This project seeks to examine the concept of immune triage, in that when faced with a healing wound and an infection at disparate sites the host must be able to deal effectively with both insults, and at times prioritize responses. We are using several cutaneous and subcutaneous trauma models that allow us to look at infiltrating cells and wound closure time.