Clinical Proteomics Center in Lung Disease

Summary

Principal Investigator: Frank Accurso
Abstract: [unreadable] DESCRIPTION (provided by applicant): [unreadable] [unreadable] Lung disease is an important cause of morbidity and mortality at all ages. There is a pressing need for development and validation of biomarkers to aid in the diagnosis and management of patients with lung disease. In particular, combinations of protein biomarkers that can be obtained non-invasively offer great promise. We propose to establish a multidisciplinary Clinical Proteomics Center in Lung Disease to rapidly develop and validate panels of protein biomarkers that can be used in diagnosis, disease prognostication, and treatment of pediatric and adult lung disorders. [unreadable] We will base our program on large, well-characterized pediatric and adult patient populations, and extensive expertise in biomarker research. The Clinical Proteomics Program will consist of a phased model of biomarker development encompassing assay validation through retrospective and prospective clinical validation to large scale application. The phased development strategy has several advantages including careful, expeditious evaluation of novel biomarkers; reduction in panel size to the minimum that is clinically useful; and maximum utilization of previously existing national disease networks. Our specific aims will be to: 1. Establish a center with five cores (Clinical, Laboratory, Data Management/Biostatistics, Educational, and Administrative) to select, validate, apply and continually improve protein biomarker panels. 2. Develop specific protein biomarker panels aimed at predicting progression of disease, assessing likelihood and significance of exacerbation, and evaluating response to treatment in Chronic Obstructive Pulmonary Disease, Asthma, Acute Lung Injury, Chronic Lung Disease of Infancy, Pulmonary Arterial Hypertension and Cystic Fibrosis. 3. Create a local and national educational and skills development program for MDs, PhDs, MD/PhDs, Laboratory Personnel and Research Coordinators, in Clinical Proteomics and 4. Establish a national resource for investigators interested in developing protein biomarkers of lung disease. [unreadable] [unreadable]
Funding Period: 2005-08-15 - 2010-07-31
more information: NIH RePORT

Top Publications

  1. pmc Evaluation of circulating proteins and hemodynamics towards predicting mortality in children with pulmonary arterial hypertension
    Brandie D Wagner
    Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Denver, Aurora, Colorado, United States of America
    PLoS ONE 8:e80235. 2013
  2. pmc Comparison of normalization methods for construction of large, multiplex amplicon pools for next-generation sequencing
    J Kirk Harris
    Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado 80045, USA
    Appl Environ Microbiol 76:3863-8. 2010
  3. pmc The applicability of urinary creatinine as a method of specimen normalization in the cystic fibrosis population
    Brandie D Wagner
    Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Denver, 13001 E 17th Place, B119, Aurora, CO, 80045, USA
    J Cyst Fibros 9:212-6. 2010
  4. ncbi Achieving asthma control in the inner city: do the National Institutes of Health Asthma Guidelines really work?
    Stanley J Szefler
    Divisions of Pediatric Clinical Pharmacology and Allergy and Immunology, Department of Pediatrics, National Jewish Health, University of Colorado Denver School of Medicine, Denver, Colo, USA
    J Allergy Clin Immunol 125:521-6; quiz 527-8. 2010
  5. ncbi Advances in pediatric asthma in 2009: gaining control of childhood asthma
    Stanley J Szefler
    Divisions of Pediatric Clinical Pharmacology and Allergy and Immunology, Department of Pediatrics, National Jewish Health, 1400 Jackson St, Rm J304, Molly Blank Building, Denver, CO 80206, USA
    J Allergy Clin Immunol 125:69-78. 2010
  6. pmc Lessons learned from variation in response to therapy in clinical trials
    Stanley J Szefler
    Division of Pediatric Clinical Pharmacology, Department of Pediatrics, National Jewish Health, Denver, CO 80206, USA
    J Allergy Clin Immunol 125:285-92; quiz 293-4. 2010
  7. pmc Measuring and improving respiratory outcomes in cystic fibrosis lung disease: opportunities and challenges to therapy
    Edith T Zemanick
    Department of Pediatrics, University of Colorado Denver, 13123 E 16th Avenue, Aurora, CO 80045, USA
    J Cyst Fibros 9:1-16. 2010
  8. pmc Leukotriene-E4 in human urine: Comparison of on-line purification and liquid chromatography-tandem mass spectrometry to affinity purification followed by enzyme immunoassay
    Michael Armstrong
    National Jewish Health, Department of Immunology, 1400 Jackson Street K924, Denver, CO 80206, USA
    J Chromatogr B Analyt Technol Biomed Life Sci 877:3169-74. 2009
  9. ncbi Managing asthma and allergies in schools: An opportunity to coordinate health care
    Stanley J Szefler
    Divisions of Pediatric Clinical Pharmacology and Allergy and Immunology, Department of Pediatrics, National Jewish Health, Denver, Colo
    J Allergy Clin Immunol 124:201-4. 2009
  10. pmc Pulmonary exacerbations in cystic fibrosis with negative bacterial cultures
    Edith T Zemanick
    Department of Pediatrics, University of Colorado Denver, Aurora, Colorado 80045, USA
    Pediatr Pulmonol 45:569-77. 2010

Detail Information

Publications41

  1. pmc Evaluation of circulating proteins and hemodynamics towards predicting mortality in children with pulmonary arterial hypertension
    Brandie D Wagner
    Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Denver, Aurora, Colorado, United States of America
    PLoS ONE 8:e80235. 2013
    ..The aim of this study was to identify a combination of clinical and molecular predictors of survival in PAH...
  2. pmc Comparison of normalization methods for construction of large, multiplex amplicon pools for next-generation sequencing
    J Kirk Harris
    Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado 80045, USA
    Appl Environ Microbiol 76:3863-8. 2010
    ..Further, population studies to examine genetic variation, which require even lower levels of sequencing, should be possible where thousands of individual bar-coded amplicons are examined in parallel...
  3. pmc The applicability of urinary creatinine as a method of specimen normalization in the cystic fibrosis population
    Brandie D Wagner
    Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Denver, 13001 E 17th Place, B119, Aurora, CO, 80045, USA
    J Cyst Fibros 9:212-6. 2010
    ..Urinary creatinine (UCr) is often used to adjust for urine analyte concentration. We aim to explore the applicability of UCr as a normalization method in a cystic fibrosis (CF) population during hospitalization...
  4. ncbi Achieving asthma control in the inner city: do the National Institutes of Health Asthma Guidelines really work?
    Stanley J Szefler
    Divisions of Pediatric Clinical Pharmacology and Allergy and Immunology, Department of Pediatrics, National Jewish Health, University of Colorado Denver School of Medicine, Denver, Colo, USA
    J Allergy Clin Immunol 125:521-6; quiz 527-8. 2010
    ..Based on the observations from the Asthma Control Evaluation study, we were impressed that a systematic guidelines-based approach improved asthma control significantly over the course of the 1-year treatment period...
  5. ncbi Advances in pediatric asthma in 2009: gaining control of childhood asthma
    Stanley J Szefler
    Divisions of Pediatric Clinical Pharmacology and Allergy and Immunology, Department of Pediatrics, National Jewish Health, 1400 Jackson St, Rm J304, Molly Blank Building, Denver, CO 80206, USA
    J Allergy Clin Immunol 125:69-78. 2010
    ....
  6. pmc Lessons learned from variation in response to therapy in clinical trials
    Stanley J Szefler
    Division of Pediatric Clinical Pharmacology, Department of Pediatrics, National Jewish Health, Denver, CO 80206, USA
    J Allergy Clin Immunol 125:285-92; quiz 293-4. 2010
    ..This information now assists the clinician in personalizing asthma treatment at the time of initiating long-term control therapy...
  7. pmc Measuring and improving respiratory outcomes in cystic fibrosis lung disease: opportunities and challenges to therapy
    Edith T Zemanick
    Department of Pediatrics, University of Colorado Denver, 13123 E 16th Avenue, Aurora, CO 80045, USA
    J Cyst Fibros 9:1-16. 2010
    ..This review highlights emerging treatments, obstacles to optimizing outcomes, and key future directions for research...
  8. pmc Leukotriene-E4 in human urine: Comparison of on-line purification and liquid chromatography-tandem mass spectrometry to affinity purification followed by enzyme immunoassay
    Michael Armstrong
    National Jewish Health, Department of Immunology, 1400 Jackson Street K924, Denver, CO 80206, USA
    J Chromatogr B Analyt Technol Biomed Life Sci 877:3169-74. 2009
    ..Results from sample integrity experiments and preliminary values of urinary LTE(4) from healthy adults and children are reported...
  9. ncbi Managing asthma and allergies in schools: An opportunity to coordinate health care
    Stanley J Szefler
    Divisions of Pediatric Clinical Pharmacology and Allergy and Immunology, Department of Pediatrics, National Jewish Health, Denver, Colo
    J Allergy Clin Immunol 124:201-4. 2009
    ..This theme issue will provide information on indoor allergens commonly present in school and day care settings, as well as information on how to manage children with asthma and food allergies in these settings...
  10. pmc Pulmonary exacerbations in cystic fibrosis with negative bacterial cultures
    Edith T Zemanick
    Department of Pediatrics, University of Colorado Denver, Aurora, Colorado 80045, USA
    Pediatr Pulmonol 45:569-77. 2010
    ..Exacerbations are often associated with characteristic airway bacteria [CF related bacteria (CFRB)]. However, some patients do not have CFRB detected by culture during exacerbations...
  11. ncbi SerpinB1 in cystic fibrosis airway fluids: quantity, molecular form and mechanism of elastase inhibition
    J Cooley
    Immune Disease Institute, Boston, MA 02115, USA
    Eur Respir J 37:1083-90. 2011
    ..The SerpinB1-elastase complex survived only briefly due to fragmentation of bound elastase, releasing cleaved SerpinB1, the molecular form in CF BALF. The findings define an innate role for SerpinB1 in CF airways...
  12. pmc Circulating cytokines and growth factors in pediatric pulmonary hypertension
    Mark Duncan
    Section of Pediatric Pulmonology, School of Medicine, University of Colorado and Children s Hospital Colorado, Aurora, CO 80045, USA
    Mediators Inflamm 2012:143428. 2012
    ..From these determinations, we aim to develop a practical, noninvasive tool to aid in the management of pediatric PH...
  13. pmc Effect of azithromycin on systemic markers of inflammation in patients with cystic fibrosis uninfected with Pseudomonas aeruginosa
    Felix Ratjen
    Division of Respiratory Medicine, Department of Pediatrics, SickKids Research Institute, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada
    Chest 142:1259-66. 2012
    ..We examined changes in systemic inflammatory markers in a doubleblind, randomized, controlled trial of oral azithromycin in patients 6-18 years of age with cystic fibrosis who were uninfected with Pseudomonas aeruginosa...
  14. ncbi New insights into asthma pathogenesis and treatment
    Stanley J Szefler
    Helen Wohlberg and Herman Lambert Chair in Pharmacokinetics, Divisions of Pediatric Clinical Pharmacology and Allergy and Immunology, Department of Pediatrics, National Jewish Health, University of Colorado School of Medicine, Denver, CO 80206, USA
    Curr Opin Immunol 23:801-7. 2011
    ....
  15. pmc Advancing asthma care: the glass is only half full!
    Stanley J Szefler
    Department of Pediatrics, National Jewish Health, University of Colorado School of Medicine, Denver, CO 80206, USA
    J Allergy Clin Immunol 128:485-94. 2011
    ..These advances should prompt the evolution of new strategies and new treatments to further reduce disease burden. It now becomes imperative to continue a focus on ways to further reduce the burden of asthma and prevent its onset...
  16. pmc Application of two-part statistics for comparison of sequence variant counts
    Brandie D Wagner
    Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Denver, Aurora, Colorado, United States of America
    PLoS ONE 6:e20296. 2011
    ..We show superior performance of the two-part statistic for analysis of sequence data. The improved performance in microbial ecology studies was independent of study type and sequence technology used...
  17. pmc Advances in pediatric asthma in 2010: addressing the major issues
    Stanley J Szefler
    Division of Pediatric Clinical Pharmacology, Department of Pediatrics, National Jewish Health, Denver, Colo 80206, USA
    J Allergy Clin Immunol 127:102-15. 2011
    ..Perhaps new directions in personalized medicine and improved health care access and communication will help maintain steady progress in alleviating the burden of this disease in children, especially young children...
  18. pmc Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation
    Frank J Accurso
    University of Colorado Denver and Children s Hospital, Aurora, CO 80045, USA
    N Engl J Med 363:1991-2003. 2010
    ..VX-770, a CFTR potentiator, has been shown to increase the activity of wild-type and defective cell-surface CFTR in vitro...
  19. ncbi Effect of an antioxidant-rich multivitamin supplement in cystic fibrosis
    Scott D Sagel
    Department of Pediatrics, The Children s Hospital, University of Colorado Denver School of Medicine, Aurora, CO, USA
    J Cyst Fibros 10:31-6. 2011
    ..Despite supplementation with standard multivitamins and pancreatic enzymes, deficiencies of vitamins D and K and antioxidants are common in cystic fibrosis (CF)...
  20. pmc Sputum desmosine during hospital admission for pulmonary exacerbation in cystic fibrosis
    Theresa A Laguna
    Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN 55455, USA
    Chest 136:1561-8. 2009
    ....
  21. ncbi A new cystic fibrosis newborn screening algorithm: IRT/IRT1 upward arrow/DNA
    Marci K Sontag
    Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, CO, USA
    J Pediatr 155:618-22. 2009
    ..To evaluate an immunoreactive trypsinogen (IRT) IRT/IRT1 upward arrow/DNA algorithm, aimed at improving sensitivity while decreasing cystic fibrosis (CF) carrier identification...
  22. ncbi Relationship between antimicrobial proteins and airway inflammation and infection in cystic fibrosis
    Scott D Sagel
    Department of Pediatrics, The Children s Hospital and University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA
    Pediatr Pulmonol 44:402-9. 2009
    ....
  23. ncbi Patterns of neutrophil serine protease-dependent cleavage of surfactant protein D in inflammatory lung disease
    Jessica Cooley
    Immune Disease Institute, Harvard Medical School, Boston, MA 02115, USA
    J Leukoc Biol 83:946-55. 2008
    ..The findings support a pre-eminent role for neutrophil elastase as the critical protease responsible for SP-D depletion in inflammatory lung disease...
  24. pmc Molecular identification of bacteria in bronchoalveolar lavage fluid from children with cystic fibrosis
    J Kirk Harris
    Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA
    Proc Natl Acad Sci U S A 104:20529-33. 2007
    ..These results show that molecular techniques provide a broader perspective on airway bacteria than do routine clinical cultures and thus can identify targets for further clinical evaluation...
  25. ncbi Proteomics in pediatric research and practice
    Stephen W Hunsucker
    Department of Pediatrics, School of Medicine, University of Colorado at Denver and Health Sciences Center, 12801 East 17th Avenue, Aurora, CO 80010, USA
    Adv Pediatr 54:9-28. 2007
  26. pmc Sputum biomarkers of inflammation in cystic fibrosis lung disease
    Scott D Sagel
    Department of Pediatrics, The Children s Hospital and University of Colorado at Denver and Health Sciences Center, Denver, Colorado 80218, USA
    Proc Am Thorac Soc 4:406-17. 2007
    ..In the future, pulmonary biomarkers will likely be useful in predicting disease progression, indicating the onset and resolution of a pulmonary exacerbation, and assessing response to current therapies or candidate therapeutics...
  27. pmc Detection of cystic fibrosis transmembrane conductance regulator activity in early-phase clinical trials
    Steven M Rowe
    Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294 0006, USA
    Proc Am Thorac Soc 4:387-98. 2007
    ..Recommendations are presented to advance our understanding of these biomarkers and to improve their capacity to predict cystic fibrosis outcomes...
  28. pmc Update in cystic fibrosis 2006
    Frank J Accurso
    Department of Pediatrics, University of Colorado Denver and Health Sciences, Denver, Colorado, USA
    Am J Respir Crit Care Med 175:754-7. 2007
  29. ncbi Advances in pediatric asthma 2006
    Stanley J Szefler
    Divisions of Pediatric Clinical Pharmacology, Allergy and Immunology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA
    J Allergy Clin Immunol 119:558-62. 2007
    ..Application of biomarkers and genetics could be useful tools in individualizing our approach to the management of childhood asthma...
  30. ncbi Genetic and physiologic correlates of longitudinal immunoreactive trypsinogen decline in infants with cystic fibrosis identified through newborn screening
    Marci K Sontag
    Department of Preventive Medicine and Biometrics, University of Colorado Health Sciences Center, Denver, Colorado, USA
    J Pediatr 149:650-657. 2006
    ..To characterize the time course and physiologic significance of decline in serum immunoreactive trypsinogen (IRT) levels in infants with cystic fibrosis (CF) by mode of diagnosis and genotype, and to examine IRT heritability...
  31. ncbi Advances in pediatric asthma in 2007
    Stanley J Szefler
    Division of Pediatric Clinical Pharmacology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA
    J Allergy Clin Immunol 121:614-9. 2008
    ..This review highlights journal articles that relate to these guideline topics...
  32. pmc Error-correcting barcoded primers for pyrosequencing hundreds of samples in multiplex
    Micah Hamady
    Department of Computer Science, UCB 430, University of Colorado, Boulder, Colorado 80309, USA
    Nat Methods 5:235-7. 2008
    ....
  33. ncbi Advances in pediatric asthma in 2008: where do we go now?
    Stanley J Szefler
    Divisions of Pediatric Clinical Pharmacology and Allergy and Immunology, Department of Pediatrics, National Jewish Health, Denver, CO 80206, USA
    J Allergy Clin Immunol 123:28-34. 2009
    ..A major step forward will be finding ways to implement the asthma guidelines...
  34. pmc Brain natriuretic peptide levels in managing pediatric patients with pulmonary arterial hypertension
    Anna Bernus
    Pediatric Cardiology, University of Colorado Denver School of Medicine, The Children s Hospital, 13123 East 16th Ave, Aurora, CO 80045, USA
    Chest 135:745-51. 2009
    ..In this study, we aimed to investigate the value of brain natriuretic peptide (BNP) in a cohort of children with PAH, with respect to monitoring disease severity as assessed by hemodynamic and echocardiographic parameters...
  35. pmc Impact of Pseudomonas and Staphylococcus infection on inflammation and clinical status in young children with cystic fibrosis
    Scott D Sagel
    Department of Pediatrics, The Children s Hospital and University of Colorado Health Sciences Center, Aurora, CO 80045, USA
    J Pediatr 154:183-8. 2009
    ..To assess the effects of Pseudomonas aeruginosa and Staphylococcus aureus infection on lower airway inflammation and clinical status in young children with cystic fibrosis (CF)...
  36. pmc Circulating RNA transcripts identify therapeutic response in cystic fibrosis lung disease
    Milene T Saavedra
    Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine, Denver, Colorado 80262, USA
    Am J Respir Crit Care Med 178:929-38. 2008
    ..Although the standard assessment of pulmonary treatment response is FEV(1), a measure of airflow limitation, the lack of systemic markers to reflect changes in lung inflammation critically limits the testing of proposed therapeutics...
  37. ncbi Decreased total serum coenzyme-Q10 concentrations: a longitudinal study in children with cystic fibrosis
    Theresa A Laguna
    Department of Pediatrics, University of Colorado, Denver, School of Medicine, Aurora, CO, USA
    J Pediatr 153:402-7. 2008
    ..To assess total serum levels of coenzyme Q(10) (Co-Q(10)), an important antioxidant, in children with cystic fibrosis (CF) and to investigate an association between Co-Q(10) level and clinical outcome...
  38. pmc Update in cystic fibrosis 2007
    Frank J Accurso
    Department of Pediatrics, University of Colorado Denver, Denver, Colorado, USA
    Am J Respir Crit Care Med 177:1058-61. 2008
  39. pmc Gene modifiers in cystic fibrosis
    Frank J Accurso
    Department of Pediatrics, Mike McMorris Cystic Fibrosis Care and Research Center, Children s Hospital, University of Colorado, Aurora, Colorado 80045, USA
    J Clin Invest 118:839-41. 2008
    ....
  40. pmc Update in cystic fibrosis 2005
    Frank J Accurso
    Children s Hospital, 1056 East 19th Avenue, Denver, CO 80218, USA
    Am J Respir Crit Care Med 173:944-7. 2006