Colorado Clinical Proteomics Program by AmnaKhan

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									Colorado Clinical Proteomics Program

    1. Pediatric Lung Disease

    2. Hypothesis and Specific Aims

    3. Colorado Clinical Proteomics Program
         - Organization
         - Setting
         - Cores
         - Networks
         - Special Features

                       Colorado Clinical Proteomics Program
          Pediatric Lung Disease

           Childhood
                           Morbidity                    Adult
Lung
                           Mortality                    Lung
Disease
                                                        Disease

Protein Biomarkers
- Assessment difficult
- Non-invasive sampling
- Small volume specimens

 Asthma, Bronchopulmonary Dysplasia,
 Cystic Fibrosis, Pulmonary Artery Hypertension
                            Colorado Clinical Proteomics Program
              Pediatric Asthma
                          - 10-35% of all children
                          - Quality of Life,
Asthma                       School Attendance
Reversible
Airway                    - Morbidity,
Obstruction                  Hospitalization 4/1000
                          - Mortality
                          - Cost

 (Sennhauser et al, 2005; Engelsvold, Omyar, 2003; Myers, 2000)
                               Colorado Clinical Proteomics Program
  Bronchopulmonary Dysplasia (BPD)

                              - 0.2% to 1% newborns
                                (10,000-40,000/yr)
BPD
• Chronic Lung Disease        - 60% Readmission rate
• Preterm Infants
                              - Increasing rate of
• Mechanical Ventilation        premature births
• All Lung Components
                              - Surfactant
                                     - Decreased severity
                                     - No change in
                                       Incidence
    (Wen et al, 2004)
                           Colorado Clinical Proteomics Program
               Cystic Fibrosis (CF)
                               - 17,000 Children

                               - 20% Hospitalized
Cystic Fibrosis
                               - Progressive Loss
• Genetic
                                 Of Lung function
• Failure of
                               - Median age of Death
 Airway Defense
                                 (25 years)

                               - Cost
     (CF Foundation Patient Registry 2003, Bethesda, MD)
                               Colorado Clinical Proteomics Program
  Pulmonary Arterial Hypertension
              (PAH)


PAH               • Mortality – 10 year 40%
• CHD
                  • Morbidity
• Idiopathic
                  • Prolonged hospitalizations
• Developmental
 Abnormalities    • 240 followed at Colorado

                   (Yung et al, 2004)

                       Colorado Clinical Proteomics Program
     Clinical Proteomics Potential
                           Asthma          BPD         CF           PAH
• Population screening                                 Yes
• Susceptibility
• Staging
• Rapid progression                       study       study
• Exacerbation
  - Identification
  - Susceptibility          study
• Response to tx            study                               study
• Toxicity with tx
• Clin Trial stratification
• Outcome Measures

• Clues to Pathogenesis
  Inflammation, Fibrosis Yes(?)             Yes         Yes         Yes
                             Colorado Clinical Proteomics Program
          Hypothesis and Specific Aims
Hypothesis: Development and Validation of Protein Bio-
Markers will lead to improved care in Pediatric Lung Disease

Aim 1. Establish a Clinical Proteomics Program in Pediatric
Lung Disease comprising five cores to develop and validate
panels of Protein Biomarkers

Aim 2. Address specific issues in Pediatric Lung Disease
  through panels of protein biomarkers:
• Asthma – frequent exacerbations, failure to respond to Tx
• CF, BPD – identification of rapid progressors
• PAH – failure to respond to Tx

Aim 3. Develop Educational Program in Clinical Proteomics

Aim 4. Develop a National Resource for NHLBI investig.
                               Colorado Clinical Proteomics Program
Colorado Clinical Proteomics Program
           – Organization
NHLBI Clinical Proteomics Steering Committee

Colorado Steering Committee - Heads of Core,
   M. Duncan, Proteomics Consultant.

 - Clinical Core – F. Accurso, MD (PI)

 - Laboratory Core – R. Harbeck, PhD

 - Data Management/Biostatistics – J. Murphy, PhD

 - Educational Core – R. Deterding, MD; L. Shroyer, PhD

 - Administrative Core – F. Accurso, MD
                             Colorado Clinical Proteomics Program
Colorado Clinical Proteomics Program
              – Setting
Childrens Hospital
Clinical, Lab, Admin   3 miles


                       National Jewish Center
                       Clinical, Lab, DMU/Biostats
                                         6 blocks
                       University of Colorado
                       Veterans Administration
                       Education, Biostats

                          Colorado Clinical Proteomics Program
                     Clinical Core
                   Director: F. Accurso, MD
Asthma: S. Szefler, MD, National Jewish
     - CAMP, ICAC

BPD: S. Abman, MD; J. Kinsella, MD
     Children’s Hospital, University
     - NHLBI funded trial of nitric oxide in prevention of BPD

PAH: S. Abman, MD; D. Ivy, MD, Children’s Hospital, Univ.
      - Local, Multicenter trials

CF: F. Accurso, MD, Children’s Hospital, Univ.
       - CF Foundation Therapeutics Development Network
Regulatory Compliance: HIPAA, Institutional Review Board
                                Colorado Clinical Proteomics Program
              Laboratory Core

          Director: R. Harbeck, PhD

Specimen Collection

          Sample Processing

                       Storage

                                     Analysis
                                     Validation
                                     Luminex Platform

 IL-1-8-10, -12, -13, 15, GM-CSF, IFN, TNF, eotaxin,
 MCP-1, RANTES, MIP-1, VEG F
                           Colorado Clinical Proteomics Program
Data Management/Biostatistics Core
                        Director: J. Murphy, PhD

  Phase 1       Phase 2          Phase 3              Phase 4            Phase 5
Exploratory   Clinical Assay   Retrospective       Prospective        Large Scale
Studies       Development/     Longitudinal         Longitudinal       Application
                Validation      Validation          Validation


 • Data Management:
       - Implementation
       - Regulatory Compliance

 • Biostatistics: J. Murphy; G. Zerbe, PhD.
       - Statistics appropriate for each Phase

                          (Pepe et al, 2001; Srinivas et al, 2002)
                                       Colorado Clinical Proteomics Program
                   Education Core
       Co-Directors: R. Deterding, ,MD, L. Shroyer, PhD

• Clinical Science Program, K30, med school curriculum
• Local, National and Web Based Goals
• Curriculum Design, Implementation, Evaluation, Disseminatio
• Trainees: Multidisciplinary backgrounds, all levels

Year 1 Year 2            Year 3                Year 4
Curriculum    Pilot Local         Full Local        Evaluate Local
Development          Start National                 National (ATS, ACCP)
                           Start Web based          Web based
                                                    Evaluate National

                                      Colorado Clinical Proteomics Program
         Clinical Study Timeline: CF

      Clinical      Year 1      Year 2           Year 3         Year 4
     Question

CF   Progression    Phase 4      Phase 4     Phase 4   Begin
      of Disease      Local       Local    Multicenter Phase 5
                   Prospective Prospective Prospective
                     N=200       N=200       N=400




                                 Colorado Clinical Proteomics Program
Colorado Clinical Proteomics Program
 1. Pediatric Lung Disease

 2. Hypothesis and Specific Aims

 3. Colorado Clinical Proteomics Program
      - Organization
      - Setting
      - Cores
      - Networks
      - Special Features
 Collaboration with M. Duncan, Proteomics,
 Randox Laboratories, Protein Arrays
                        Colorado Clinical Proteomics Program
Experience with Matrices Other
    than Plasma or Serum
• Sputum (Sagel et al. 2001)

• BAL (Khan et al. 1995)

• Bronchial Brushing (Wooldridge et al, 2004)

• Breath Condensate

• Urine
   - Proteomic Study of Urinary Biomarkers in CF
     Exacerbation
   - Collaboration with M. Duncan and S. Hunsucker

                           Colorado Clinical Proteomics Program
  Protein Biomarker Timeline:
Immunoreactive Trypsinogen (IRT)

 1979                 1991             1995                   2004

Pilot CF            Validated        Clinical            CDC,
Screening           (Hammond         Benefit             CF Found.
(Eliot et al)       et al)           (Farrell            Endorse-
                                     et al)              ment

           Colorado Screening Program (n>1,000,000)

                We need to do better.

                             Colorado Clinical Proteomics Program

								
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