Jennifer Alexander-Brett, MD, PhD

Assistant Professor

Internal Medicine
Pathology and Immunology

Immunology Program

Keywords:

cytokine networks, epithelial cell biology, pulmonary diseases, biochemistry, animal models, human studies

Research:

My research focuses on respiratory immunobiology, with a particular interest in cytokine pathways associated with adult lung epithelial progenitor cells. My research background includes the application of structural biology, biochemistry and cell biology to immunological systems. I currently employ an array of techniques spanning model systems to molecular analyses to address the mechanistic basis of pulmonary diseases.

My initial mechanistic studies will build upon prior expertise developed during my postdoctoral study, involving the IL-33 cytokine system in chronic airway disease. IL-33 is a dual-functioning nuclear factor and secreted cytokine (“nucleokine”) that has been found to participate in the development of inflammatory diseases involving virtually every organ system. I have identified lung progenitor epithelial cells as the source of increased IL-33 production in chronic airway disease, and further showed that cellular danger signals could induce release of IL-33 in vitro. Although we have established that progenitor-derived IL-33 production is a key feature of airway disease pathogenesis, the mechanisms by which nuclear IL-33 is trafficked, processed and released from these cells in cytokine form are substantial knowledge gaps that have stymied efforts to target its function in disease. Accordingly, I plan to address the cellular mechanism by which airway disease-associated danger signals induce nuclear export, proteolytic processing and non-classical vesicular trafficking to release active IL-33 cytokine from progenitor epithelial cells. To address these questions, I employ a range of techniques including mouse models, 3D epithelial cell culture, live cell imaging, and structural, biochemical and molecular interaction studies. These mechanistic studies may yield more effective treatments for COPD, asthma and other respiratory diseases. Furthermore, as the relevance of IL-33 continues to expand to inflammatory disease in multiple organ systems, there is potential for an even broader impact of this work.

Future directions of the lab include development of progenitor cell-based assays to screen for new cytokine pathways that modulate lung progenitor cell function and application to pulmonary diseases that exhibit defective epithelial repair.

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