The JAB lab integrates mucosal immunology, epithelial stem cell biology and protein biochemistry to understand the mechanistic basis of pulmonary diseases. We have expertise in biochemistry, structural and cell biology applied to immunological systems, respiratory disease animal models and analysis of human clinical specimens. We currently apply this broad range of techniques to explore mechanism in airway disease.
Historically, the lab has been interested in the molecular and cellular basis of IL-33 activation and signaling. This cytokine is produced by expanded lung epithelial stem cells in chronic airway disease and is a key mediator of type-2 inflammation in COPD and asthma. A major knowledge gap in the field of IL-33 biology has been the mechanism by which IL-33 is trafficked, processed and released from airway cells. We have discovered that IL-33 can be tonically secreted from lung epithelial cells in concert with a subset of endosomal-derived extracellular vesicles commonly referred to as ‘exosomes’. We are actively investigating the molecular basis of IL-33 recruitment to exosome biogenesis pathways, characterizing key interacting partners and investigating the impact on IL-33 signaling. We also have an interest in epigenetic regulation of IL-33 expression and alternative splicing patterns that facilitate cytokine secretion.
We have expanded our studies of extracellular vesicles (EVs) as respiratory mucosal signaling platforms under homeostatic and disease conditions. We have expertise in the biochemical and biophysical characterization of extracellular vesicles, manipulation of respective biogenesis pathways and characterization of EVs derived from biospecimens. Our work to date has been informed by transcriptomic and proteomic profiling of EVs from COPD lung biospecimens. Through this work we have identified potential novel disease pathways which may be amenable to targeting for therapeutic benefit. We are also applying our current approach to investigate the role of epithelial derived EVs in the mechanism of chronic lung allograft dysfunction (CLAD). We are exploring the EV-associated factors that signal dysfunctional epithelial repair as an early step in the pathologic sequence of CLAD. To perform this work, we have established a comprehensive prospective post-lung transplant biospecimen repository.