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Getting from Genes to Function in Lung Disease

Executive Summary

In the soon-to-be “post-Genome-Wide Association Study (GWAS)” era, many novel genes or genetic variants have been identified and implicated in the pathogenesis of lung disease. Yet, a large proportion of the genetic variance remains unexplained. New approaches need to be undertaken to hone in on and characterize functional (disease causing) variation, its role in disease pathogenesis, and to fully characterize the genetic architecture of rare and complex lung diseases. Such strategies will need to incorporate genomic approaches that integrate studies of individual genes with pathways and regulatory networks, and with model systems for elucidating function in a biological context.

The National Heart, Lung, and Blood Institute convened a workshop on September 3-4, 2009 to bring together experts in genetics, genomics, proteomics, networks, and informatics along with experts in pulmonary biology and medicine, with the goal of cross-fertilization and generation of needed next-step initiatives that can be translated into research needs and opportunities for NHLBI in the important scientific area of “Getting from Genes to Function in Lung Disease.” Many of the attendees represented major NHLBI-funded consortia in lung disease. In addition, promising young K12 scholars developing careers in the genetics and genomics of lung disease were invited to attend and participate in the discussions.

Following a series of overview talks on lung genetics, lung diseases, and extended phenotyping (phenomics), there were state-of-the art presentations on selected topics including: data integration, system genetics, functional validation in model organisms and in humans, and translational and integrative genomics in the clinical setting. Concepts helpful for framing future research opportunities were reviewed, short and long range strategic plans developed, and new research directions and scientific opportunities identified and prioritized.

Recommended Priority Research Areas

  1. Functionally characterize genes (and variation) identified by GWAS to be involved in the pathogenesis of lung disease using integrated –omic (genetics, genomics, trascriptomics, proteomics, metabolomics, phenomic, etc) approaches across scientific disciplines.
  2. Explore mechanisms of transcriptional regulation (eQTLs and epigenetic modifications) and changes over time/development in different cell types and in response to environmental stimuli in humans and mice, and by incorporating systems genetics and network building.
  3. Develop model systems (including man, mice, flies, zebrafish, worms, and yeast) to understand how genes function in complex biological systems.
  4. Conduct genomic studies of markers that are common for the same phenotype across different lung diseases (defined comprehensively to include molecular, developmental, cellular, physiologic, anatomic, imaging etc.)
  5. Integrate approaches to identifying disease genes using existing datasets to understand the function of genes in complex biological systems.
  6. Establish comprehensive Lung Biology Centers (Virtual Lung Centers) to integrate scientists across disciplines (genetics, bioinformatics, systems biology, and phenotype/clinical) to comprehensively study how genetic variations (in a broad sense)(gxg, gxe, epigenetics, integrated/comparative approaches) function biologically in complex genetic systems.
  7. Train young investigators to use bioinformatic tools that will allow mining of existing genetic and genomic data sets to address hypotheses on the pathogenesis of lung disease.
  8. Develop tools/animal models of lung disease (to share with the community)

Future research related to each of these categories should be addressed using integrated approaches across disciplines (genetics, bioinformatics, systems biology, and phenotype/clinical) that include one or more of the following: “-omic” technologies, systems genetics/biology and pathway/network analysis, animal models lung disease, human studies in ethnically/racially diverse populations, multiple lung diseases, mining of data from existing resources. The latter could include, but is not limited to, data from clinical trial cohorts and population-based cohorts, studies of transcriptional and proteomic profiling in relevant tissues, mouse models of lung disease, and repositories of banked tissues.

Workshop Members


  • Atul Butte, M.D., Ph.D., Stanford University
  • Jack Elias, M.D., Yale University
  • Aldons Jake Lusis, Ph.D., University of California, Los Angeles
  • Carole Ober, Ph.D., University of Chicago
  • David Schwartz, M.D., National Jewish Health


  • Michael J Bamshad, M.D., University of Washington
  • Kathleen Barnes, Ph.D., Johns Hopkins University
  • Eugene Bleecker, M.D., Wake Forest University
  • Pat Brooks, Pacific Biosciences
  • Esteban G. Burchard, M.D., M.P.H., University of California, San Francisco
  • Damien Chaussabel, Ph.D., Baylor Research Institute
  • Bohao Chen, M.D., University of Chicago
  • Geofffrey L. Chupp, M.D., Yale University
  • F. Sessions Cole., M.D., Washington University School of Medicine
  • William Cookson, M.D., D Phil, FRCP, National Heart and Lung Institute, Royal Brompton Campus, Imperial College of London
  • David B. Corry, M.D., Baylor College of Medicine
  • Nancy Cox, Ph.D., University of Chicago
  • James D. Crapo, M.D., National Jewish Health
  • Ronald G. Crystal, M.D., Cornell University
  • Joe (Skip) G. Garcia, M.D., University of Chicago
  • Frank Gilliland, M.D., Ph.D., University of Southern California
  • Hakon Hakonarson, M.D., Ph.D., Children’s Hospital of Philadelphia
  • Howard J. Huang, M.D., Washington University School of Medicine
  • Naftali Kaminski, M.D., University of Pittsburgh School of Medicine
  • Michael Knowles, M.D., University of North Carolina, Chapel Hill
  • Abigail Lara, M.D., University of Colorado, Denver
  • Stephanie London, M.D., Dr.Ph., National Institute of Environmental Health Sciences
  • Joseph Loscalzo, M.D., Ph.D., Brigham and Women’s Hospital
  • James E. Loyd, Ph.D., Vanderbilt University School of Medicine
  • Fernando D. Martinez, M.D., University of Arizona
  • Nuala Meyer, M.D., University of Pennsylvania School of Medicine
  • Deborah A. Meyers, Ph.D., Wake Forest University
  • Deborah Nickerson, Ph.D., University of Washington
  • Dan Nicolae, Ph.D., University of Chicago
  • Marcelo A. Nobrega, M.D., Ph.D., University of Chicago
  • Rudy Pascual, M.D., Wake Forest University
  • Vincinio de Jesus Perez, M.D., Ph.D., Stanford University School of Medicine
  • Diego A. Preciado, M.D., Ph.D., Children’s National Medical Center
  • Benjamin Raby, M.D., Brigham and Women’s Hospital
  • Dan M. Roden, M.D., Vanderbilt University School of Medicine
  • Eric Schadt, Ph.D., Pacific Biosciences
  • Sunita Sharma, M.D., M.P.H., Channing Laboratory, Harvard Medical School
  • Edwin Silverman, M.D., Ph.D., Brigham and Women’s Hospital
  • Avrum Spira, M.D., M.Sc., Boston University School of Medicine
  • Donata Vercelli, M.D., University of Arizona
  • Scott T. Weiss, M.D., M.S., Brigham and Women’s Hospital
  • Marsha Wills-Karp, Ph.D., Cincinnati Children’s Hospital Medical
  • Prescott G. Woodruff, M.D., M.P.H., University of California, San Francisco
  • Fred Wright, Ph.D., University of North Carolina, Chapel Hill
  • Mark M. Wurfel, M.D., Ph.D., University of Washington
  • John R. Yates, Ph.D., The Scripps Research Institute
  • Fei Zou, Ph.D., University of North Carolina, Chapel Hill


  • Susan Banks-Schlegel, Ph.D., Division of Lung Diseases
  • Sandra Colombini-Hatch, M.D., Division of Lung Diseases
  • Weiniu Gan, Ph.D., Division of Lung Diseases
  • Dorothy Gail, Ph.D., Division of Lung Diseases
  • James P. Kiley, Ph.D., Division of Lung Diseases
  • Alan M. Michelson, M.D., Ph.D., Office of the Director

Last Updated March 2011

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