I’m a physician-scientist in the Division of Pulmonary, Allergy, Critical Care and Sleep Medicine. My interest is to understand the relationship between infection and the host response in asthma as many aspects of the innate immune response to allergies and also infectious agents, such as rhinovirus and Mycoplasma pneumoniae, are dysfunctional in asthma. This dysfunction contributes to frequent exacerbations (asthma attacks) and decline in lung function over time. My laboratory has demonstrated that the activity of two important aspects of the innate immune response, surfactant protein A (SP-A) and Src homology protein-1 (SHP-1), are reduced in asthma compared to normal subjects and most likely driven by genetic and post-translational mechanisms. A second line of investigation is to determine how hyaluronan, a glycosaminoglycan expressed ubiquitously, contributes to airway remodeling in asthma, and epithelial cell compression or stretch similar to bronchoconstriction in human asthma, activates these cells initiate and perpetuate the inflammatory process. My lab employs samples isolated directly from the lungs of well-phenotyped patients with mild, moderate and severe asthma and normal volunteers obtained by bronchoscopy. We are now studying specific animal models such that observations can move from man to mouse and back. These projects will move the field forward to understand the pathobiology of exacerbations and remodeling in asthma.
In addition to translational opportunities, my group performs clinical trials in asthma and COPD (chronic obstructive pulmonary disease) evaluating new therapies, pharmacogenetics, obesity, metabolomic profiles and airway physiology. I am one of the principal investigators in the National Institutes of Health (NIH) Clinical Trials group, AsthmaNet, and the American Lung Association Research Network. This experience would involve exposure/interaction with research participants, bronchoscopy, IRB and budgets.
Project 1: Evaluate the role of surfactant protein A in the host response to an important cytokine in asthma, interleukin-13 in mouse models of asthma and evaluation of airway epithelial cells from well-phenotyped patients and normal controls ex vivo. There is the opportunity to evaluate parts of the SP-A protein (peptides) that span active domains as a potential therapeutic intervention to resolve allergic inflammation.
Project 2: Evaluate the role of surfactant protein A and the related peptides in the host response to specific infections that are known to cause asthma exacerbations such as rhinovirus and Mycoplasma pneumoniae. This project would involve mouse models of infection and airway epithelial cells from asthmatic patients obtained by bronchoscopy.
Project 3: Determine the effect of epithelial stretch/compression on cellular activation and cross talk with structural cells using an ex vivo compression system and cells from well phenotyped patients with asthma and normal controls. The hypothesis is that bronchoconstriction itself, independent of inflammation, promotes airway remodeling in asthma. Remodeling is a process where the airway is changed permanently and is associated with decreased response to bronchodilating medications.
Project 4: Involvement in clinical trials evaluating new therapies or heterogeneity in response to therapy in mild, moderate and severe asthma, depending upon the intervention. These trials are supported by either NIH or industry. There are several to consider at any one time.