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Edwin K. Silverman, MD, PhD

Associate Professor of Medicine
Harvard Medical School

Associate Physician
Brigham and Women's Hospital

 

ed.silverman@channing.harvard.edu



Research Affiliations

Alpha-1 Foundation


Research Interests

My goal is to combine research in the genetic epidemiology of complex diseases with clinical practice in pulmonary and critical care medicine. In an effort to merge my doctoral training in genetic epidemiology with my clinical training in pulmonary and critical care medicine, I have focused my research efforts on the genetic epidemiology of chronic obstructive pulmonary disease (COPD) and asthma. The primary goal of my research has been to combine field, laboratory, and analytical approaches to address the challenging problems involved in elucidating the genetic influences in complex diseases. Field work involves applying my pulmonary and critical care training to study design and data collection of relevant phenotypes in obstructive lung diseases. Laboratory work includes supervising sample processing and implementing genotyping and sequencing assays. Analytical work involves employing my training in genetic epidemiology to apply a range of methods including assessment of risk to relatives, linkage analysis, association studies, and rare variant analysis.

I am involved in a variety of genetic epidemiology studies at the Channing Laboratory and Pulmonary and Critical Care Division of Brigham and Women’s Hospital. For the past fifteen years, I have been the Principal Investigator of an extended pedigree study designed to identify novel genetic determinants of early-onset COPD (Boston Early-Onset COPD Study). We are in the process of performing two multicenter COPD genetics studies which will include genome-wide association analysis. I am the Principal Investigator of the Transcontinental COPD Genetics Study, which is investigating genetic determinants of COPD in diverse ethnic groups, and I am one of two Principal Investigators of the Genetic Epidemiology of COPD Study (COPDGene), which is creating a large cohort of COPD cases and controls with comprehensive pulmonary phenotyping (including chest CT scans) for genome-wide association analysis. In addition, I am the Principal Investigator of a collaborative study to identify genetic modifiers of severe alpha-1 antitrypsin deficiency. I am also collaborating with GlaxoSmithKline on several studies of COPD genetics, including the International COPD Genetics Network (I am one of the two Principal Investigators) and the ECLIPSE Study (I am on the Steering Committee). In addition to COPD genetics research, I have also served as a co-investigator on a variety of family-based association studies of the genetics of asthma, including the Childhood Asthma Management Program Genetics Ancillary Study, the Genetics of Latino Americans Study, and a study of the genetics of asthma in Costa Rica.


Selected Publications

Silverman EK, Pierce JA, Province MA, Rao DC, Campbell EJ. Variability of pulmonary function in alpha 1-antitrypsin deficiency: Clinical correlates. Ann Int Med 1989;111:982-991. [abstract]

Silverman EK, Chapman HA, Drazen JM, Weiss ST, Rosner B, Campbell EJ, O'Donnell WJ, Reilly JJ, Ginns L, Mentzer S, Wain J, Speizer FE. Genetic epidemiology of severe early-onset COPD: risk to relatives for airflow obstruction and chronic bronchitis. Am J Respir Crit Care Med. 1998 Jun;157(6 Pt 1):1770-8. [abstract]

Burchard EG, Silverman EK, Rosenwasser LJ, Borish L, Yandava C, Pillari A, Weiss ST, Hasday J, Lilly CM, Ford J, Drazen JM. Association between a sequence variant in the IL-4 gene promoter and FEV1 in asthma. Am J Respir Crit Care Med. 1999 Sep;160(3):919-22. [abstract]

Celedon JC, Speizer FE, Drazen JM, Weiss ST, Campbell EJ, Carey VJ, Reilly JJ, Ginns L, Silverman EK. Bronchodilator responsiveness and serum total IgE levels in families of probands with severe, early-onset COPD. Eur Resp J 1999; 14:1009-1014. [abstract]

Silverman EK, Weiss ST, Drazen JM, Chapman HA, Carey V, Campbell EJ, Denish P, Silverman RA, Celedon JC, Reilly JR, Ginns L, Speizer FE. Gender-related differences in severe, early-onset chronic obstructive pulmonary disease. Am J Resp Crit Care Med 2000; 162: 2152-2158. [abstract]

Grasemann H, Yandava CN, Storm van's Gravesande K, Deykin A, Pillari A, Ma J, Sonna LA, Lilly C, Stampfer MJ, Israel E, Silverman EK, Drazen JM. A neuronal NO synthase (NOS1) gene polymorphism is associated with asthma. Biochem Biophys Res Commun. 2000 Jun 7;272(2):391-4. [abstract]

Wechsler ME, Grasemann H, Deykin A, Silverman EK, Yandava CN, Israel E, Wand M, Drazen JM. Exhaled nitric oxide in patients with asthma: Association with NOS1 genotype. Am J Resp Crit Care Med 2000; 162:2043-2047. [abstract]

Silverman EK, Mosley J, Rao DC, Palmer LJ, Province M, Elston RC, Weiss ST, Campbell, EJ. Linkage analysis of alpha 1-antitrypsin deficiency: Lessons for complex diseases. Hum Hered 2001; 52: 223-32. [abstract]

Israel E, Drazen JM, Liggett SB, Boushey HA, Cherniak RM, Chinchilli VM, Cooper DM, Fahy JV, Fish JE, Ford JG, Kraft M, Kunselman S, Lazarus SC, Lemanske RF Jr, Martin RJ, McLean DE, Peters SP, Silverman EK, Sorkness CA, Szefler SJ, Weiss ST, Yandava CN. The effect of the Beta 2-Adrenergic receptor on the response to regular use of albuterol in asthma. Int Arch Allergy Immunol. 2001 Jan-Mar;124(1-3):183-6. [abstract]

Celedon JC, Silverman EK, Weiss ST, Wang B, Fang Z, Xu X. Application of an algorithm for the diagnosis of asthma in Chinese families: Limitations and alternatives for the phenotypic assessment of asthma in family-based genetic studies. Am J Respir Crit Care Med. 2000 Nov;162(5):1679-84. Erratum in: Am J Respir Crit Care Med. 2002 Sep 1;166(5):774. [abstract]

Silverman EK, Mosley JD, Palmer LJ, Barth M, Senter JM, Brown A, Drazen JM, Kwiatkowski DJ, Chapman HA, Campbell EJ, Province MA, Rao DC, Reilly JJ, Ginns LC, Speizer FE, Weiss ST. Genome-wide linkage analysis of severe, early-onset chronic obstructive pulmonary disease: Airflow obstruction and chronic bronchitis phenotypes. Hum Molec Genet 2002; 11:623-632. [abstract]

Demeo DL, Lange C, Silverman EK, Senter JM, Drazen JM, Barth MJ, Laird N, Weiss ST for the CAMP Research Group. Univariate and Multivariate Family-based Association Analysis of the IL-13 Arg130Gln Polymorphism in the Childhood Asthma Management Program. Genet Epidemiol. 2002 Nov;23(4):335-48. [abstract]

Silverman EK, Palmer LJ, Mosley JD, Barth M, Senter JM, Brown A, Drazen JM, Kwiatkowski DJ, Chapman HA, Campbell EJ, Province MA, Rao DC, Reilly JJ, Ginns LC, Speizer FE, Weiss ST. Genome-wide Linkage Analysis of Quantitative Spirometric Phenotypes in Severe, Early-Onset Chronic Obstructive Pulmonary Disease. Am J Hum Genet. 2002 May;70(5):1229-39. Epub 2002 Mar 25. [abstract]

Palmer LJ, Celedon JC, Chapman HA, Speizer FE, Weiss ST, Silverman EK. Genome-wide linkage analysis of bronchodilator responsiveness and post-bronchodilator spirometric phenotypes in chronic obstructive pulmonary disease. Hum Mol Genet. 2003 May 15;12(10):1199-210. Erratum in: Hum Mol Genet. 2003 Aug 15;12(16):2085. [abstract]

Demeo DL, Campbell EJ, Barker AF, Brantly ML, Eden E, McElvaney NG, Rennard SI, Sandhaus RA, Stocks JM, Stoller JK, Strange C, Turino G, Silverman EK. IL10 polymorphisms are associated with airflow obstruction in severe alpha 1-antitrypsin deficiency. Am J Respir Cell Mol Biol. 2008 Jan;38(1):114-20. Epub 2007 Aug 9. [abstract]

Vestbo J, Anderson W, Coxson HO, Crim C, Dawber F, Edwards L, Hagan G, Knobil K, Lomas DA, Macnee W, Silverman EK, Tal-Singer R; the ECLIPSE Investigators. Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints. Eur Respir J. 2008 Apr;31(4):869-73. Epub 2008 Jan 23. [abstract]

Vansteelandt S, DeMeo DL, Su J, Smoller J, Murphy AJ, McQueen M, Schneiter K, Celedon JC, Weiss ST, Silverman EK, Lange C. Testing and estimating gene-environment interactions in family-based association studies. Biometrics. 2008 Jun;64(2):458-67. Epub 2007 Oct 25. [abstract]

Lasky-Su J, Lyon HN, Emilsson V, Thorleifsson G, Thorsteinsdottir U, Stefansson K, Lazarus R, Klanderman B, Raby BA, Soto-Quiros ME, Avila L, Silverman EK, Celedón JC, Weiss ST, Heid IM, Kronenberg F, Vollmert C, Illig T, Wichmann H-E, Fox CS, Levy D, O’Donnell CJ, Laird N, Ding X, McQueen M, Molony C, Schadt E, Butler J, Ardlie K, Hirschhorn J, Papoutsakis C, Dedoussis G, Lange C. On the replication of genetic associations: Timing can be everything! Am J Hum Genet 2008; 82: 849-858. [abstract]

Cho MH, Ciulla D, Klanderman BJ, Raby BA, Silverman EK. High-resolution melting curve analysis of genomic and whole-genome amplified DNA. Clin Chem 2008;54(12): 2055-8. PMID: 19042988. [abstract]

Bhattacharya S, Srisuma S, Demeo DL, Shapiro SD, Bueno R, Silverman EK, Reilly JJ, Mariani TJ. Molecular Biomarkers for Quantitative and Discrete COPD Phenotypes. Am J Respir Cell Mol Biol. 2009 Mar;40(3):359-67. Epub 2008 Oct 10. PMID: 18849563. [abstract]

Lomas DA, Silverman EK, Edwards LD, Miller BE, Coxson HO, Tal-singer R. Evaluation of COPD Longitudinally to identify Predictive Surrogate Endpoints (ECLIPSE) investigators. Evaluation of serum CC-16 as a marker for COPD in the ECLIPSE cohort. Thorax. 2008 Dec;63(12):1058-63. Epub 2008 Aug 29. [abstract]

Foreman MG, Demeo DL, Hersh CP, Carey VJ, Fan VS, Reilly JJ, Shapiro SD, Silverman EK. Polymorphic variation in surfactant protein B is associated with COPD exacerbations. Eur Respir J. 2008 Oct;32(4):938-44. Epub 2008 Jun 11. PMID: 18550614. [abstract]

Patel BD, Coxson HO, Pillai SG, Agustí AG, Calverley PM, Donner CF, Make BJ, Müller NL, Rennard SI, Vestbo J, Wouters EF, Hiorns MP, Nakano Y, Camp PG, Nasute Fauerbach PV, Screaton NJ, Campbell EJ, Anderson WH, Paré PD, Levy RD, Lake SL, Silverman EK, Lomas DA. Airway wall thickening and emphysema show independent familial aggregation in chronic obstructive pulmonary disease. International COPD Genetics Network. Am J Respir Crit Care Med. 2008 Sep 1;178(5):500-5. Epub 2008 Jun 19. [abstract]

DeMeo DL, Campbell EJ, Brantly ML, Barker AF, Eden E, McElvaney NG, Rennard SI, Stocks JM, Stoller JK, Strange C, Turino G, Sandhaus RA, Silverman EK. Heritability of Lung Function in Severe Alpha-1 Antitrypsin Deficiency. Hum Hered. 2009;67(1):38-45. Epub 2008 Oct 17. [abstract]

Kim WJ, Hersh CP, DeMeo DL, Reilly JJ, Silverman EK. Genetic Association Analysis of COPD Candidate Genes with Bronchodilator Responsiveness. Respir Med. 2009 Apr;103(4):552-7. Epub 2008 Dec 25. [abstract]

Lomas DA, Silverman EK, Edwards LD, Locantore NW, Miller BE, Horstman DH, Tal-Singer R. Serum Surfactant Protein D is Steroid Sensitive and Associated with Exacerbations of COPD. Eur Respir J. 2009 Jul;34(1):95-102. Epub 2009 Jan 22. [abstract]

Hersh CP, Hansel NN, Barnes KC, Lomas DA, Pillai SG, Coxson HO, Mathias RA, Rafaels NM, Wise RA, Connett JE, Klanderman BJ, Jacobson FL, Gill R, Litonjua AA, Sparrow D, Reilly JJ, Silverman EK. Transforming Growth Factor Beta Receptor-3 is Associated with Pulmonary Emphysema. Am J Respir Cell Mol Biol. 2009 Jan 8. [Epub ahead of print] [abstract]

Kim WJ, Silverman EK, Hoffman E, Criner GJ, Mosenifar Z, Sciurba FC, Make BJ, Carey V, San Jose Estepar R, Diaz A, Reilly JJ, Martinez FJ, Washko GT. CT Metrics of Airway Disease and Emphysema in Severe COPD. Chest. 2009 May 1. [Epub ahead of print]. [abstract]

Pillai SG, Ge D, Zhu G, Kong X, Shianna KV, Need AC, Feng S, Hersh CP, Bakke P, Gulsvik A, Ruppert A, Lødrup Carlsen KC, Roses A, Anderson W, Rennard SI, Lomas DA, Silverman EK, Goldstein DB, ICGN Investigators. A Genome-wide Association Study in Chronic Obstructive Pulmonary Disease (COPD): Identification of Two Major Susceptibility Loci. [abstract]

Wilk JB, Chen T-H, Gottlieb DJ, Walter RE, Nagle MW, Brandler BJ, Myers RH, Borecki IB, Silverman EK, Weiss ST, O'Connor GT. A Genome-wide Association Study of Pulmonary Function Measures in the Framingham Heart Study. PLoS Genet. 2009 Mar;5(3):e1000429. Epub 2009 Mar 20. [abstract]

Washko GR, Dransfield MT, Estépar RS, Diaz A, Matsuoka S, Yamashiro T, Hatabu H, Silverman EK, Bailey WC, Reilly JJ. Airway Wall Attenuation: A Biomarker of Airway Disease in Subjects with COPD. J Appl Physiol. 2009 Jul;107(1):185-91. Epub 2009 Apr 30. [abstract]

Cho MH, Ciulla DM, Klanderman BJ, Hersh CP, Litonjua AA, Sparrow D, Raby BA, Silverman EK. Analysis of Exonic Elastin Variants in Severe, Early-Onset COPD. Am J Respir Cell Mol Biol. 2009 Jun;40(6):751-5. Epub 2008 Nov 21. [abstract]

Castaldi PJ, Hersh CP, Reilly JJ, Silverman EK. Genetic Associations With Hypoxemia and Pulmonary Arterial Pressure in COPD. Chest. 2009 Mar;135(3):737-44. Epub 2008 Nov 18. [abstract]