Bruce David Levy

Dr. Levy is an Assistant Professor in Medicine at Brigham and Women’s Hospital in the Pulmonary and Critical Care Medicine Division and serves as the Medical Residency Director for Academics and Career Development. Research undertaken in the Levy laboratory focuses on the roles of endogenous counter-regulatory mediators in the lung. The lab’s mission is “to identify novel pathways and cellular targets that promote resolution of pulmonary inflammation or injury and to establish naturally-derived small molecules as templates for rational new drug design.”

To this end, we have identified a novel series of bioactive polyisoprenyl phosphates in neutrophils (Levy et al, Nature. 1997). One of these compounds, presqualene diphosphate, undergoes rapid phosphate remodeling upon cell activation and carries inhibitory properties in bioassays of neutrophil activation, such as superoxide anion generation. These were the first results to indicate novel roles for cholesterol biosynthetic intermediates as lipid-derived anti-inflammatory signals. We have also elucidated mechanisms for lipid mediator class switching during acute inflammation in vivo that lead to the formation of lipoxins, a potent family of eicosanoids with leukocyte-specific counter-regulatory properties (Levy et al. Nature Immunol. 2001). Recently, we identified protective roles for lipoxins and lipoxin A4 receptors in the development of allergy, airway inflammation and airway hyper-responsiveness (Levy et al. Nature Med. 2002). Determining the molecular mechanism of action for polyisoprenyl phosphate signaling, elucidation of pivotal presqualene diphosphate metabolic enzymes, as well as uncovering the potential for lipoxins and related compounds to promote resolution of pulmonary inflammation are major areas of current emphasis in the laboratory.