Professor, Department of Medicine (Pulmonary and Critical Care), UCSF
Dr. Lazarus is an inbred product of the University of California, having received his A.B. from Berkeley, his M.D. from Irvine, and training in Internal Medicine and Pulmonary & Critical Care Medicine at UCSF. Drafted into military service during the Viet Nam era, he spent 2 years as Chief of Pulmonary Medicine and Co-Director of the ICU at Andrews Air Force Base in Washington, D.C. before returning to UCSF for additional research training in the Cardiovascular Research Institute. Since joining the faculty at UCSF in 1983, Dr. Lazarus has directed basic and clinical research on the mechanisms and treatment of asthma, COPD, and other airway diseases. He is an Attending Physician on the Pulmonary Consult Service, the Adult Pulmonary Function Laboratory, and the Chest Faculty Practice at UCSF-Moffitt-Long Hospital, and has been Director of the Chest Faculty Practice, Director of the Medical Specialty Practices, and Interim Chief of the Division of Pulmonary and Critical Care Medicine. Currently he is Director of the Training Program in Pulmonary and Critical Care Medicine and Associate Director of the Adult Pulmonary Laboratory.
Dr. Lazarus' research has focused on the role of inflammatory cells and mediators in regulating function of the lung and airways in obstructive lung diseases. After working in whole animals and organ systems, he developed continuous mastocytoma cell lines that share many important features of normal human mast cells. These cells served as a unique model system for mast cell biology as well as a source of mast cell-derived mediators to examine the role of these mediators in important biological processes.
Studies of mast cell mediators led to a series of investigator-initiated clinical research projects to examine the role of leukotrienes in chronic asthma and in mediating the bronchoconstrictor response to inhaled sulfur dioxide; the role of tachykinins in mediating the airway hyperresponsiveness, airway inflammation, and symptoms of chronic asthma; and the correlation between elastase and elastolytic activity in the sputum of patients with chronic bronchitis and physiological measures of lung function. In collaboration with Drs John Fahy, George Caughey, and Jay Nadel, Dr. Lazarus examined the effect of sputum proteases on airway inflammation, and the effect of inflammatory mediators on regulation of airway mucin gene expression and mucin secretion (via the EGF-receptor).
These studies provided the infrastructure for several successful competitive applications to the NIH to participate in Clinical Research Networks. In 1993, Drs. Boushey, Lazarus, and Fahy were awarded one of 6 Asthma Clinical Research Network (ACRN) Centers in the US, and their application was again successful in an open competition in 2003. This network conducts multicenter clinical trials to examine important mechanisms in the treatment and pathogenesis of asthma. In addition to serving on the Steering Committee of the Network, responsible for the design and implementation of all studies, Dr. Lazarus was the Lead Investigator on 2 major ACRN projects: one, a study that examined clinical outcomes and inflammatory biomarkers in subjects treated with inhaled corticosteroids or a long-acting ß-agonist, was published in JAMA, and was responsible for a change in asthma management guidelines. Dr. Lazarus also led a study that demonstrated that asthmatics who smoke have a blunted response to inhaled corticosteroids – apparently because smoking regulates transcription factors related to airway inflammation.
In 2003, Dr. Lazarus built upon studies of mucus hypersecretion and airway function to prepare a successful application to the NIH/NHLBI to participate as one of 7 sites in the COPD Clinical Research Network (CCRN). As Principal Investigator of this award, Dr. Lazarus led studies to examine biomarkers as predictors of COPD exacerbations, and to explore the role of arachidonic acid metabolites in the pathogenesis of COPD exacerbations. Dr. Lazarus Chairs the Steering Committee of this Network.
Dr. Lazarus is also Co-PI of the new (in 2009) AsthmaNet, an NHLBI network funded for 7 years to examine clinical outcomes and mechanisms of asthma. He is the lead investigator of a study of TH2 high vs TH2 low asthma phenotypes, to be launched in 2012.
Finally, in collaboration with Prescott Woodruff, Dr. Lazarus is a Co-Investigator of the new SPIROMICS network, an NHLBI-sponsored project to identify subpopulations of COPD patients that are similar with respect to molecular mechanisms of disease.