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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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The Clinical and Translational Science Award Program:
Transdisciplinary Teams in Cancer Prevention Research
11th Annual International
Conference on Frontiers in Cancer Prevention ResearchOctober 16, 2012
Steven Dubinett, MDDirector, Clinical and Translational Science Institute Senior Associate Dean and Associate Vice Chancellor for Research, UCLA www.ctsi.ucla.edu
UC-ReX
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.
National, regional and institutional teams
National CTSA Program
CTSA Constoria
Team Science
Outpatient & community based research
Inpatient GCRC
Training in clinical and translational team science
Regional and national consortia linked for collaboration
Traditional training
Individual academic medical centers
OLD NEW
Purpose of the National CTSA Program
Providing an infrastructure for clinical and translational research
Transdisciplinary team scienceIndividual investigator
s
NIH CTSA Consortium
UCLA CTSI Clinical and Translational Science
Institute
www.ctsi.ucla.edu
Team Science-How do we get there?
• Facilitate - infrastructure • Reward - funding• Recognize - promotions• Training - in the team environment
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
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)
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
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Examples of Team Science Awards
Stroke/cardiovascular disease in underserved minority populations:
• working with community partners, design and test interventions to reduce risk of disease
Barbara Vickrey, MD, MPH
DMH-UCLA-USC Public Mental Health Translational Research Consortium:
• in partnership with LA County and USC, implement best practices within the public mental health system
Joel Braslow, MD, PhD
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 clinical trials in melanoma
Antoni Ribas, MD
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 capacity
First Year accomplishments
400 ongoing research projects 80 new protocols 4800 out-patient
& 210 in-patient stays
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What is translational research?
UCLA translational investigation extends from molecules to society
Translating knowledge gained from laboratory science into clinical practice to improve health.
The aim of translational research is to produce new:
• therapeutics• medical devices• tools for diagnosing disease• community engagement research/ implementation
UC BRAIDUniversity of California - Biomedical
Research, Acceleration, Integration & Development
http://www.ucbraid.org/
a new initiative…building on success of 5 CTSAs
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UC Biomedical Research Acceleration Integration 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
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UC Biomedical Research Acceleration Integration and Development (UC-BRAID)
Investigator
• IRB harmonization• Master contracting
• Integrated Research Data Repository
• Harmonizing biobanking
UCSF
UC Davis
UCLA
UC San Diego
UC Irvine
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UC Biomedical Research Acceleration Integration and
Development (UC-BRAID)
UCs UCLA CTSI
Partner
InstitutionsLocal
Delivery
Network
PatientLA County
health system
Community-
based clinics
& centers
Harbor /
LA BioMed
Charles Drew
University
UCLA
UCSF
UC Irvine
UC Davis
UC San Diego
Cedars-Sinai
UC-ReX
UC-ReXhttp://
www.ucbraid.org/informaticsmdashu
c-rex.html
UC-ReX User Interface
Science of Team Science
• growing interest and investment in large-scale, team-based research initiatives to address complex and multi-faceted problems that require cross-disciplinary collaboration
• The science-of-team-science field - concerned especially with understanding and managing circumstances that facilitate or hinder the effectiveness of team science initiatives. Stokols, Am J Prev Med 2008
Science of Team Science
Clin Transl Sci. 2010 Oct
Training in Team Science
Starting early
Creating new mechanisms
Changes in Bronchial Epithelium in Relation to Cigarette Smoking and in Relation to Lung Cancer
Oscar Auerbach, A. P. Stout, E. Cuyler Hammond, and Lawrence Garfinkel NEJM August 10, 1961
23
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
Two Models of Cancer Development and Progression
normaltissue
in situcancer
disseminatedcancer
aggressive metastasis
(e.g., a stem cell expressing Snail)
DNA damage
DNA damage
normaltissue
in situcancer
dissemination
metastasis
aggressive metastasis
Model 1 Model 2
Adapted from Sánchez-García NEJM 2009
disseminated cancer
Snail drives programs of inflammation, migration/invasion, angiogenesis and stem cell phenotype expansion in HBEC
HBEC-Snail
Air-Liquid Interface 3D Model
HBEC-Vector
E-cad Ki67SnailH&E
AAHSquamous Metaplasia
Snail in Premalignancy
Q-RT-PCR Validation
ZEB 1
mR
NA
exp
ress
ion
Snail
1
E-cadherinmR
NA
exp
ress
ion
Inflammation-mediated promotion of EMT
IL-1b, PGE2, TGF-b
++Snail
• apoptosis resistance• angiogenesis• decreased E-cadherin• enhanced inflammation
• stem cell phenotypes • drug resistance• metastasesE-cadherin red; COX-2 brown
PGE2
Which features of pulmonary premalignancy portend transformation and progression?
AAH
Squamous Metaplasia
What proteins/genes are evident in situ in premalignancy?
…and which are critical for driving transformation and
progression?
HBEC-Snail
Air-Liquid Interface 3D Model
HBEC-Vector
E-cad Ki67SnailH&E
Tonya WalserKostyantyn KrysanDavid Elashoff Leonard RomeJay Lee Edward Garon Gina Lee Fran Rosen Sherven SharmaMinu SrivastavaFelicita BaratelliYing LinMi-Heon LeeMichael Fishbein Dean Wallace Denise AberleFereidoun AbtinRobert SuhBrian Gardner Brigitte GompertsMin HuangMaie St. John
Xiaoyan CuiSaswati HazraElvira LiclicanEileen HeinrichJie LuoWen MaoYing LinZhe JingLi ZhuYuan LinStacy ParkJeanette GrantNicole RodriguezPaul PaganoRui LiSahil PatelPuja KachrooAik Ooi Dorthe ShaueGrigoriy ShekhtmanAvi Spira (Boston University)
Marc Lenburg (Boston University)
Ignacio Wistuba (MD Anderson)
Pierre Massion (Vanderbilt)
Jerry Shay (UT Southwestern)
John Minna (UT Southwestern)
Patient advocates & foundations
Supported by: NCI EDRN · Lung Cancer SPORE · VA · DOD · LungEVITY · UCLA
CTSI · Tobacco Related Disease Res Program · Broad Foundation · LCMC
Team Science
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