10/16 AACR Team Science Presentation


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UCLA CTSI Director, Steven Dubinett, MD, participated in the 11th Annual American Association for Cancer Research (AACR) Frontiers in Cancer Prevention Research International Conference and discussed the advantages of the CTSI during his educational session on “The Clinical and Translational Science Award Program: Transdisciplinary Teams in Cancer Prevention Research” on Tuesday, October 16th.

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  • Our CTSI proposes to create a collaborative culture in which practice-changing innovation is not the exception but the rule
  • 10/16 AACR Team Science Presentation

    1. 1. The Clinical and Translational Science Award Program: Transdisciplinary Teams in Cancer Prevention Research 11th Annual International Conference on Frontiers in Cancer Prevention Research October 16, 2012Steven Dubinett, MDDirector, Clinical and Translational Science InstituteSenior Associate Dean and Associate Vice Chancellor for Research, UCLAwww.ctsi.ucla.edu
    2. 2. Disclosure Information11th Annual International Conference on Frontiers in Cancer Prevention Research The Clinical and Translational Science Award Program: Transdisciplinary Teams in Cancer Prevention Research Steven Dubinett I have no financial relationships to disclose. – and – I will not discuss off label use and/or investigational use in my presentation.
    3. 3. National, regional and institutional teamsNational CTSAProgramCTSA ConstoriaTeam Science
    4. 4. Purpose of the National CTSA Program Providing an infrastructure for clinical and translational research OLD NEW Inpatient GCRC Outpatient & community based research Individual investigators Transdisciplinary team science Traditional Training in clinical and translational training team science Individual academic Regional and national consortiamedical centers linked for collaboration
    5. 5. NIH CTSA Consortium
    6. 6. UCLA CTSIClinical and Translational Science Institute Team Science- How do we get there? • Facilitate - infrastructure • Reward - funding • Recognize - promotions • Training - in the team environment www.ctsi.ucla.edu
    7. 7. CTSI Research Funding• Pilot Program: 53 awards totaling $1.8 million• Team Science Awards: up to $200K for team science proposals• Core Services Vouchers: awards of up to $10K each• Business of Science Center collaborations: fellowships and team awards• CTSI Scholars: mentored research program for new faculty; $30K each annually• Shared Resources Consortium: support for instrumentation and existing and proposed cores 7
    8. 8. Current Team Science Award Partners• AIDS Institute• Jonsson Comprehensive Cancer Center• Broad Stem Cell Research Center• Cardiovascular• Neuroscience• Patient Safety Institute (PSI)• Center for AIDS Research (CFAR) 8
    9. 9. Current Seed Grant Partners• Center for Autism Research & Treatment (CART)• Cousins Center for Psychoneuroimmunology• Women’s Health Center• Resource Centers for Minority Aging Research / Center for Health Improvement for Minority Elders (RCMAR/CHIME)• Pepper Center 9
    10. 10. Examples of Team Science AwardsBarbara Vickrey, MD, MPH Stroke/cardiovascular disease in underserved minority populations: • working with community partners, design and test interventions to reduce risk of diseaseJoel Braslow, MD, PhD DMH-UCLA-USC Public Mental Health Translational Research Consortium: • in partnership with LA County and USC, implement best practices within the public mental health systemAntoni Ribas, MD Overcoming acquired resistance to B-Raf targeting in melanoma using phospho-proteomics and microfluidics: • Building a comprehensive program for signaling discovery and diagnostics to guide kinase inhibitor 10 clinical trials in melanoma
    11. 11. Clinical and Translational Research Center (CTRC)Ambulatory Clinical Research Facilities• 7 private rooms, infusion rooms, 2 procedure rooms• >20,000 sq ft outpatient area• Clinical and Research Sleep Center• Interview and conference rooms• A service center including pharmacy and sample processing• 23 hour capacityFirst Year accomplishments 400 ongoing research projects 80 new protocols 4800 out-patient & 210 in-patient stays
    12. 12. What is translational research? UCLA translational investigation extends from molecules to societyTranslating knowledge gained from laboratoryscience into clinical practice to improve health.The aim of translational research is to producenew:• therapeutics• medical devices• tools for diagnosing disease• community engagement research/ implementation 12
    13. 13. CTSA Regional ConsortiaUniversity of California, Los Angeles
    14. 14. UC BRAIDUniversity of California - Biomedical Research, Acceleration, Integration & Development a new initiative… building on success of 5 CTSAs http://www.ucbraid.org/
    15. 15. UC Biomedical Research AccelerationIntegration and Development (UC-BRAID)• A committee of the CTSA PIs at UC Davis, San Diego, San Francisco, Irvine and Los Angeles• contracting, informatics and IRBs• Drug discovery and development• Biobanking and global consent• Future inclusion of other partner institutions 15
    16. 16. UC Biomedical Research AccelerationIntegration and Development (UC-BRAID) 16
    17. 17. UC Biomedical Research AccelerationIntegration and Development (UC-BRAID) 17
    18. 18. UC-ReXhttp://www.ucbraid.org/i nformaticsmdashuc- rex.html
    19. 19. UC-ReX User Interface
    20. 20. Science of Team Science• growing interest and investment in large-scale, team-based research initiatives toaddress complex and multi-facetedproblems that require cross-disciplinarycollaboration•The science-of-team-science field -concerned especially with understandingand managing circumstances that facilitateor hinder the effectiveness of team scienceinitiatives. Stokols, Am J Prev Med 2008
    21. 21. Science of Team Science Clin Transl Sci. 2010 Oct
    22. 22. Training in Team ScienceStarting earlyCreating new mechanisms
    23. 23. Changes in Bronchial Epithelium in Relation to CigaretteSmoking and in Relation to Lung CancerOscar Auerbach, A. P. Stout, E. Cuyler Hammond, and Lawrence GarfinkelNEJM August 10, 1961 Rui Li Paul Pagano Jeannette Grant Kostyantyn Krysan Elvira Liclican Tonya Walser Felicita Baratelli Gina Lee Stacy Park Brian Gardner Puja Kachroo Ying Lin Wen Mao Zhe Jing 23
    24. 24. Two Models of Cancer Development and Progression Model 1 Model 2 normal normal tissue tissue (e.g., a stem cell expressing Snail) metastasis in situ cancer dissemination DNA damagedisseminated in situ cancer cancer DNA damage aggressiveaggressive disseminated metastasismetastasis cancer Adapted from Sánchez-García NEJM 2009
    25. 25. Snail drives programs of inflammation, migration/invasion, angiogenesis and stem cell phenotype expansion in HBEC Snail in Premalignancy Squamous AAH Metaplasia Air-Liquid Interface 3D ModelHBEC-Vector Q-RT-PCR H&E Snail E-cad Ki67 ValidationHBEC- Snail
    26. 26. Inflammation-mediated promotion of EMT IL-1b, PGE2, TGF-b Snail mRNA expression ++Snail ZEB 1 PGE2 • apoptosis resistance • angiogenesis 1 • decreased E-cadherinmRNA expression • enhanced inflammation E-cadherin • stem cell phenotypes • drug resistance E-cadherin red; COX-2 brown • metastases
    27. 27. Which features of pulmonary premalignancy portend transformation and progression? Squamous AAH MetaplasiaWhat proteins/genes are evident in situ in premalignancy? …and which are critical for driving transformation and progression? Air-Liquid Interface 3D Model HBEC- Vector H&E Snail E-cad Ki67 HBEC- Snail
    28. 28. Team ScienceTonya Walser Maie St. John Avi Spira (Boston University)Kostyantyn Krysan Xiaoyan Cui Marc Lenburg (Boston University)David Elashoff Saswati Hazra Ignacio Wistuba (MD Anderson)Leonard Rome Elvira Liclican Pierre Massion (Vanderbilt)Jay Lee Eileen Heinrich Jerry Shay (UT Southwestern)Edward Garon Jie Luo John Minna (UT Southwestern)Gina Lee Wen Mao Patient advocates &Fran Rosen Ying Lin foundationsSherven Sharma Zhe JingMinu Srivastava Li ZhuFelicita Baratelli Yuan LinYing Lin Stacy ParkMi-Heon Lee Jeanette GrantMichael Fishbein Nicole RodriguezDean Wallace Paul PaganoDenise Aberle Rui LiFereidoun Abtin Sahil PatelRobert Suh Puja KachrooBrian Gardner Aik OoiBrigitte Gomperts Dorthe ShaueMin Huang Grigoriy Shekhtman Supported by: NCI EDRN · Lung Cancer SPORE · VA · DOD · LungEVITY · UCLA CTSI · Tobacco Related Disease Res Program · Broad Foundation · LCMC
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