Avrum Spira, M.D., M.Sc.
Faculty and Fellows
Professor of Medicine, Pathology & Laboratory Medicine, and Bioinformatics
Chief, Division of Computational Biomedicine, Boston University School of Medicine
Director, Translational Bioinformatics Program, Clinical and Translational Science Institute
Medical School: McGill University
Internship: University of Toronto
Residency: University of Toronto
Fellowship: Boston University
Master’s/PhD programs: Masters Degree in Bioinformatics, College Of Engineering, Boston University
- Internal Medicine
- Pulmonary Medicine
- Critical Care Medicine
- Lung cancer and COPD genomics
- Smoking and airway gene expression
- Critical Care Medicine
- Pulmonary Medicine
Dr. Spira is an Associate Professor in the Departments of Medicine, and Pathology and Bioinformatics and is 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. He directs the Bioinformatics Program in the Pulmonary 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.
- 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
- Millien G, Beane J, Lenburg M, Lu J, Spira A, Ramirez M. Characterization of the mid-foregut transcriptome identifies genes regulated during lung bud induction. Mechanisms of Development . 8:124-39, 2008
- 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
- Zhang X, Liu G, Lenburg M, Spira A. Comparison of smoking-induced gene expression on Affymetrix exon and 3′ based expression arrays. Genome Informatics. 18:247-257, 2007
- Shah V., Sridhar S., Beane J., Brody J., Spira A. SIEGE: Smoking Induced Epithelial Gene Expression Database. Nucleic Acids Res. 33: D573-9. 2005
- Spira A*, Beane J*, Pinto-Plata V*, Kadar A, Liu G, Shah V, Celli B, Brody, J.S. Gene Expression Profiling of Human Lung Tissue from Smokers with Severe Emphysema. Am J Respir Cell Mol Biol. 31: 601-610. 2004. *contributed equally and should be considered co-first authors
- 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
- Spira A, Beane J, Schembri F, Liu G, Yang X, Ding C, Gilman S, Cantor C, and Brody J. Noninvasive method for obtaining RNA from buccal mucosa epithelial cells for gene expression profiling. Biotechniques. 36:484-87, 2004
- Hoffman A, Awad T, Spira A, Palma J, Webster T, Wright G, Buckley J, Davis R, Hubbell E, Jones W, Tibshirani R, Tompkins R, Triche T, Xiao W ,West M, Warrington J. Expression profiling — best practices for data generation and interpretation in clinical trials. Nature Reviews Genetics. 5: 229-38, 2004.
- Spira A, Carroll D, Aziz Z, Liu G, Shah V, Kornfeld H, Keane J. Apoptosis Genes in Human Alveolar Macrophages Infected with Virulent or Attenuated M. tuberculosis. Am J Respir Cell Mol Biol. 29(5):545-51, 2003
- Spira A*, Powell C*, Derti A, DeLisi C, Liu G, Borczuk A, Busche S, Sugarbaker D, Bueno R, Brody J. Gene Expression in lung adenocarcinomas of smokers and nonsmokers. Am J Respir Cell Mol Biol. 29:157-162, 2003 *contributed equally and should be considered co-first authors
- A gene expression signature of emphysema-related lung destruction and its reversal by the tripeptide GHK
- Characterizing the impact of smoking and lung cancer on the airway transcriptome using RNA-Seq.
- Airway PI3K pathway activation is an early and reversible event in lung cancer development.
- MicroRNAs as modulators of smoking-induced gene expression changes in human airway epithelium.
- Airway Epithelial Gene Expression in the Diagnostic Evaluation of Smokers with Suspect Lung Cancer
- Effects of cigarette smoke on the human airway epithelial cell transcriptome