Kim Lu

Project Title: Leukocytes, the Glucocorticoid Receptor, and Exercise: A New Way to Vision Obesity-Related Asthma in Children

Dr. Lu’s overall research theme investigating the role of the glucocorticoid receptor (GR) related to children with obesity-related asthma and exercise has developed based on her clinical experience as a pediatric pulmonologist (asthma and fitness) and laboratory/translational skills evaluating the GR in leukocytes. Despite the significant knowledge gained over the past two decades in asthma pathobiology, there is a significant gap in our understanding of the glucocorticoid receptor (GR), one of the fundamental mechanisms through which asthma treatment is based. Through a CTSA collaboration innovation award with the J. Craig Venter Institute, she proposes to focus on characterizing newly identified leukocyte subpopulations that express GR as potential biomarkers in children with asthma using cutting edge flow cytometry and computer analytics. This proposal is built on Dr. Lu’s exciting recently published and preliminary data that have identified a novel inflammatory mechanism in pediatric asthma involving the glucocorticoid receptor (GR) on leukocytes. Using advanced flow cytometry analytics developed by collaborators at J. Craig Venter Institute, Stanford and UCSD, they found that a short period of exercise training in children with asthma led to a remarkable disappearance of GR on a subpopulation of leukocytes. This novel observation is particularly relevant to asthma since physical activity is one of the most common and debilitating triggers of bronchoconstriction in affected children. Asthma is now recognized as a heterogeneous group of disorders involving inflammation in the respiratory system(1). Treatment success in children, particularly in obese and poor disadvantaged children, is far from optimal(2). The research results over the past several years demonstrate Dr. Lu’s ability to successfully design and execute hypothesis-driven complex studies in children, and to master cutting edge technologies, such as advanced flow cytometry and machine-learning based big-data analytics, that can transform our understanding of the relationship between asthma and inflammation in children. The next phase of Dr. Lu’s research will accelerate identification of these GR- expressing cell populations and their underlying mechanism(s) in asthma. These advances could lead to discovery of novel cell-based biomarkers for diagnostic and therapeutic applications in asthma.

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