Faculty Profile:  JANET S. LEE, MD

Dr. Janet Lee’s Research

Broadly speaking, our laboratory studies host susceptibility to lung injury and the role of phagocytes that orchestrate and participate in the injury response as well as aid in the repair and resolution of inflammation.  We utilize a repertoire of relevant injury models including bacterial pneumonia, sterile LPS-induced lung injury, chronic cigarette smoke exposure and RBC transfusion to study innate immune activation signals triggered during lung inflammation and subsequent de-activation signals requisite for appropriate resolution.

One focus of our laboratory is how macrophages respond to damaged cells and the triggering of anti-inflammatory cytokine production involved in the resolution process following lung injury.  When this process is disrupted, the host is unable to adequately orchestrate de-activation signals and there is persistence of inflammation and injury.  When there is too much, there is immunosuppression.  RBC transfusion is an independent risk factor for the development of acute respiratory distress syndrome in at risk populations.  Our group aims to understand how macrophages respond to constituents of RBC transfusates that include aged, damaged red cells, membrane-derived microparticles and hemoglobin breakdown products.

Another focus of our laboratory is mechanisms underlying persistent neutrophilic lung inflammation. We are currently interested in thrombospondin-1 (TSP-1), a multifunctional extracellular matrix glycoprotein, involved in cell-cell and cell-matrix interactions and released during inflammation. TSP-1 is protective during lung injury and aids in the resolution of sterile inflammation by facilitating the production of the anti-inflammatory cytokine IL-10 by macrophages.  However, during chronic neutrophilic lung inflammation such as in bronchiectasis and COPD, excessive TSP-1 expression from persistent platelet and neutrophil activation may paradoxically contribute to impaired microbial killing, leading to a vicious cycle of inflammation and tissue destruction.

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