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Cancer Center Support Grant Site Review Date

Signals, Pathways and Targets Program Leaders: John Lowengrub , Ph.D. Marian L. Waterman, Ph.D. 2011 Chao Family Cancer Center Retreat Palm Springs. Cancer Center Support Grant Site Review Date. Cancer Center Support Grant Site Review Date. Rationale.

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Cancer Center Support Grant Site Review Date

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  1. Signals, Pathways and Targets Program Leaders: John Lowengrub, Ph.D. Marian L. Waterman, Ph.D. 2011 Chao Family Cancer Center Retreat Palm Springs Cancer Center Support Grant Site Review Date Cancer Center Support Grant Site Review Date

  2. Rationale • Cancer is a complex adaptive system with dynamic regulatory pathways (DevBiol, Cell Biol, Biochem) • Modeling dynamic interactions is critical for understanding progression and response to treatment (Systems Biol) • The SPT program reflects this multi-disciplinary approach to cancer

  3. Systems, Pathways and Target Program: 56 members

  4. The SPT Program Cancer Relevant SPT Publications, 1/2011 – 9/2011

  5. Signals, Pathways and Targets: Program Metrics $17,134,815 Total Annual Direct Costs (peer reviewed) $2,695,977(NCI)

  6. Systems Organs Pathways Targets

  7. Systems, Pathways and Targets Program Themes Systems Organs Pathways Targets

  8. Program Co-Leader: John Lowengrub Multi-Scale Modeling Solid Tumors, Microenvironment Wnt, BMP, Hypoxia, HGF Cancer Stem Cells • Angiogenesis • Macrophages • Fibroblasts • Immune cells NIH GO Grant. PIs: Lander, Lowengrub

  9. 13 National Centers for Systems Biology (NIH P50) PI: Lander (SPT) Other key personnel: SPT: Calof, Bardwell, Nie, Wan OIB:Gratton Intestinal organoids http://www.systemscenters.org/ Renewal (2011): Theme B (Calof): Control of Growth and Morphogenesis SPT: Edwards, Lander, Lowengrub, Nie, Waterman

  10. New research initiative • Cellular cross-talk in the human colon cancer microenvironment NIH/PPG: Expected submission: May 2012 PI: Hughes (ABT); Project leaders: Waterman (SPT), Hughes (ABT), George (ABT), Lowengrub (SPT); Core directors: Hughes, Edwards (SPT), Hui Waterman George Hughes Lowengrub

  11. Systems Modeling Drug Resistance Virus Dynamics Komarova Wodarz Organs Chronic Myeloid Leukemia Oncolytic Viruses BcrAbl BcrAbl mutants Cancer Cells

  12. Bench to Bedside: Krolewski, Fruehauf, Lilly, Dash Systems Prostate Cancer Cell Death Dasatinib BcrAbl Src Prostate Disease Oriented Team (DOT) Clinical Trials Open for Accrual: 11 Trials developed directly from DOT activities: 3 (UCI-10-11; UCI-10-41; UCI-11-02)

  13. Dr. Bang Hoang Wnt Signaling in Sarcomas Osteosarcoma Wnt cMet Neuropilin

  14. Dr. Bang Hoang Wnt Signaling in Sarcomas Wnt Signaling and Metastasis in Osteosarcoma WIF-1, Frzb 2011 Kappa Delta Ann Doher Vaughn Award DruggableWnt Target Genes c-MET Neuropilin Career Development Award: 2011 - 2014 NIH K08 CA11600

  15. Bench to Bedside: Dr. David Fruman Leukemia PI3K PP242 INK128 mTOR

  16. Next-Gen mTOR inhibitors Dr. David Fruman

  17. A New Target: Dr. Aimee Edinger Systems Leukemia Nutrient Transporter Ceramide Synthase

  18. Oct. 2011 PI: Aimee Edinger (SPT) Collaborators: David Fruman (SPT), Michael Lilly (SPT)

  19. Scientific Highlights Proteomic Tools Dr. Lan Huang, PhD: Mass Spectrometry • New protein tagging strategies: tandem tags, in vivo biotinylation • Novel cross-linking chemistries: click-chemistry, novel spacers • Rapid Protein Complex Isolation • Proteasome network – collaboration with Dr. Peter Kaiser • Global Ubiquitination, NeddylationNetwork – collaboration with Dr. Peter Kaiser • RNA/Protein complexes (MS2-BioTRAP) – NCI IMAT R21CA133275 Tsai BP, Wang X, Huang L, Waterman ML. 2011. Mol Cell Proteomics. “Quantitative Profiling of In Vivo-assembled RNA-Protein Complexes Using a Novel Integrated Proteomic Approach” planned: NCI IMAT R33 Multi-PI RO1

  20. SPT Discoveries: Moving Targets Closer to the Bedside Systems Organs Pathways CSB Targets

  21. p53 Rescue Scientific Highlights: NCI R01 2010 A Functional Census of p53 Cancer and Suppressor Mutants Dr. Peter Kaiser (SPT; PI) and Dr. Rick Lathrop (CSB; contact PI) Currently: in silicoscreen of >2,000,000 small molecules small molecule synthesis and test in cells

  22. Scientific Highlights The p53 Team Biology Kaiser Lab, PI (SPT) Biological Chemistry Chemistry Chamberlin Lab (CSB) Pharmaceutical Sciences Machine Learning Lathrop Group, PI (CSB) Computer Science Molecular Biology Hatfield Lab Computational Biology Research Laboratory Molecular Dynamics Amaro Group Pharmaceutical Sciences Mouse Genetics Lee Lab (ABT) Biological Chemistry Structural Biology Cocco Lab (NMR) (CSB) Luecke Lab (X-ray) (CSB) Molecular Biology and Biochemistry Cancer Center - Value Added NIH/NCI T32 #CA113265 GHTF Core CFCCC Seed grants

  23. The SPT Program • Challenges • Size • Diversity of Discipline • Geographic Location (UCIMC, Main Campus, SOM) • Meeting the Challenges • Communication • Monitoring • Meetings • Goal: Linking Basic and Clinical groups • Disease Oriented Teams • John Krolewski (SPT): Prostate Cancer • Rob Edwards (SPT)/Jason Zell (PPS): Colon Cancer

  24. Systems, Pathways and Targets Program Co-Leaders: Dr. John Lowengrub, Dr. Marian Waterman Systems Organs Pathways Targets

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