Avrum Spira, M.D., M.Sc.
Professor of Medicine, Pathology & Laboratory Medicine, and Bioinformatics
Alexander Graham Bell Professor of Healthcare Entrepreneurship
Chief, Division of Computational Biomedicine, Boston University School of Medicine
Director, Translational Bioinformatics Program, Clinical and Translational Science Institute
M.D., University of Toronto, Toronto, Canada, 1996
Internal Medicine Residency, University of Toronto, Toronto, Canada, 1999
M.Sc., Bioinformatics, Boston University, College of Engineering, Boston, MA, 2002
Pulmonary & Critical Care Fellowship, Boston University Medical Center, Boston, MA, 2003
Dr. Spira is a Professor in the Departments of Medicine, and Pathology and Bioinformatics and is founding Chief of the Division of Computational Biomedicine in the Department of Medicine at BUSM. He attends in the Medical Intensive Care Unit at Boston Medical Center and directs the Translational Bioinformatics Program in the Clinical and Translational Science Institute at Boston University.
Dr. Spira’s laboratory research interests focus on applying genomic and bioinformatics tools to the translational study of lung cancer and Chronic Obstructive Lung Disease (COPD), with the ultimate objective of developing novel diagnostics and therapeutics that can directly impact clinical care. He is funded as a Principal Investigator through three institutes at the NIH including the NCI, NHLBI, and NIEHS as well as the Department of Defense. His research program centers around the concept that inhaled toxins create a “field of injury” in all exposed airway epithelial cells, and that by measuring gene expression in a relatively pure population of these cells, one can develop a gene-expression profile that reflects the physiological response to and damage from the toxin. The importance of the “field-of-injury” concept is that it allows for the detection of lung disease in tissues that are more readily assayed than the diseased lung itself.
His lab has characterized the impact of cigarette smoking on intra-thoracic (lobar bronchi) and extra-thoracic (mouth and nasal) airway epithelial cell gene expression, and he has leveraged this approach to develop a bronchial airway gene-expression biomarker for the early detection of lung cancer that is currently being validated in a multicenter clinical trial. His lab has also extended this “field of injury” paradigm to the premalignant and lung cancer screening settings, potentially allowing personalized genomic approaches to lung cancer chemoprophylaxis and therapy. This disease-specific airway “field of injury” concept is also being applied to Chronic Obstructive Lung Disease (COPD), to better understand the molecular diversity of COPD, both for developing subtype-targeted therapies and for developing biomarkers that would allow identification of biologically distinct forms of COPD. Most significantly, his lab has identified airway gene-expression biomarkers that can be used to monitor disease activity and response to therapy in COPD, and they have connected gene expression signatures of disease in clinical samples to in vitro small molecule perturbations to move from bedside to bench and identify new uses for existing drugs as potential COPD therapeutics. Finally, we are exploring gene-expression profiles in nasal and buccal epithelium as biomarkers of the physiological response to inhaled toxins and their potential role as lung disease biomarkers in large-scale population studies.
Campbell. J.D., J.E. McDonough, J.E. Zeskind, D.V. Pechkovsky, C.-A. Brandsma, M. Suzuki, J.V. Gosselink, G. Liu, Y.O. Alekseyev, J. Xiao, X. Zhang, S. Hayashi, J.D. Cooper, W. Timens, D.S. Postma, D.A. Knight, M.E. Lenburg*, J.C. Hogg*, A. Spira*. A gene expression signature of emphysema-related lung destruction and its reversal by the tripeptide GHK. Genome Medicine. 4(8):67, Aug 2012. * contributed equally
Beane J, Cheng L, Soldi R, Zhang X, Liu G, Anderlind C, Lenburg ME, Spira A*, Bild A*. SIRT1 pathway dysregulation in the smoke-exposed airway epithelium and lung tumor tissue. Cancer Res. Sept 2012. * contributed equally
Beane J, Vick J, Schembri F, Anderlind C, Gower A, Campbell J, Luo L, Zhang XH, Xiao J, Alekseyev YO, Wang S, Levy S, Massion PP, Lenburg M, Spira A. Characterizing the impact of smoking and lung cancer on the airway transcriptome using RNA-Seq. Cancer Prev Res (Phila). 4(6):803-17, 2011.
Gustafson AM, Soldi R, Anderlind C, Scholand MB, Qian J, Zhang X, Cooper K, Walker D, McWilliams A, Liu G, Szabo E, Brody J, Massion PP, Lenburg ME, Lam S, Bild AH, Spira A. Airway PI3K pathway activation is an early and reversible event in lung cancer development. Sci Transl Med. 2(26):26ra25, 2010.
Spira A, Steiling K. Topics in genetics and genomics: Gene Expression. In: UpToDate, Basow DS (Ed), UpToDate, Waltham, MA 2010.
Zhang X, Sebastiani P, Liu G, Schembri F, Zhang X, Dumas YM, Langer EM, Alekseyev Y, O’Connor GT, Brooks DR, Lenburg ME*, Spira A*. Similarities and differences between smoking-related gene expression changes in nasal and bronchial epithelium. Physiol Genomics. 41(1):1-8, 2010. * contributed equally
Steiling K, Kadar AY, Bergerat A, Flanigon J, Sridhar S, Shah V, Ahmad QR, Brody JS, Lenburg ME, Steffen M, Spira A. Comparison of proteomic and transcriptomic profiles in the bronchial airway epithelium of current and never smokers. PLoS One. 4(4):e5043, 2009.
Schembri F, Sridhar S, Perdomo C, Gustafson AM, Zhang X, Ergun A, Lu J, Liu G, Zhang X, Bowers J, Vaziri C, Ott K, Sensinger K, Collins JJ, Brody JS, Getts R, Lenburg ME, Spira A. MicroRNAs as modulators of smoking-induced gene expression changes in human airway epithelium. Proc Natl Acad Sci USA. 106(7):2319, 2009.
Beane J, Sebastiani P, Whitfield T, Steiling K, Lenburg M, Spira A . A Prediction Model for Lung Cancer Diagnosis that Integrates Clinical and Genomic Features. Cancer Prevention Research . 1: 56-64, 2008.
Sridhar S, Schembri F, Zeskind J, Shah V, Gustafson A, Steiling K, Liu G, Dumas Y, Zhang S, Brody J, Lenburg M, Spira A. Smoking-induced gene expression changes in the bronchial airway are reflected in nasal and buccal epithelium. BMC Genomics . 9:259, 2008.
Beane J, Sebastiani P, Liu G, Brody J, Lenburg M, Spira A. Reversible and Permanent Effects of Tobacco Smoke Exposure on Airway Epithelial Gene Expression. Genome Biology. 8: R201, 2007.
Spira A, Beane J, Shah V, Steiling K, Liu G, Schembri F, Gilman S, Dumas Y, Calner P, Sebastiani P, Sridhar S, Beamis J, Lamb C, Keane J, Lenburg M, Brody J. Airway Epithelial Gene Expression in the Diagnostic Evaluation of Smokers with Suspect Lung Cancer. Nature Medicine. 13:361-6. 2007.
Spira A, Beane J, Shah V, Liu G, Schembri F, Yang X, Palma J, Brody J. Effects of Cigarette Smoke on the Human Airway Epithelial Cell Transcriptome. Proc Natl Acad Sci USA. 101:10143-8, 2004.