Molecular Targets Development Program, CCR, NCI

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Molecular Targets Development Program, CCR, NCI
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Translational Research at the CCR

Genetics Genomics
Integrated Systems Biology
Molecular Targets Molecular Oncology
CCR Clinical Program
HIV/AIDS
Immunology, Immunotherapy Immunoprophylaxis
Intramural/Extramural
Imaging Biomarkers
Advanced Biomedical Technologies
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Center for Cancer Research

• 15 clinical branches
• 38 basic sciences laboratories
• gt 330 principal investigators

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MTDP Mission
A549
SNB19
MTDP
HTS Data
Lab Bench Data
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MTDP Mission

• Collaborate with CCR investigators to develop and
  apply molecular target-specific assays
• Screen the NCI natural products repository and
  other sources of chemical diversity
• Identify and characterize target-specific
  compounds
• Provide active compounds to collaborating labs
  for use as bioprobes

MTDP
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Target Consortium
PIs
Staff Scientists
Molecular Target/Pathway
Lab Chiefs
Postdoctoral Fellows
Proposal
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Initial Feasibility

• Quality control of reagents and cell lines
• Reagent stability
• Reagent specificity and binding characteristics
• Cellular growth characteristics
• Time frame of assay
• Stable end point
• Signal to noise ratio
• Availability of appropriate controls
• Availability of required equipment
• Availability of sufficient reagents

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Priority Areas

• Screening Platforms
• Natural Products
• Protein Chemistry and Molecular Biology
• Libraries
• Imaging
• Information Technology

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Screening Platforms
Enzymatic - FRET Protein-Protein Interactions -
Time-Resolved Fluorrescence -
Electrochemiluminescence Cell-based -
Colorimetric - Fluorometric -
Luminescent Cell-Imaging - GFP Translocation -
GFP Expression
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MTDP Ongoing Projects
Project Rationale Project Rationale
MDM2/ ubiquitination p53 induced apoptosis gp78 ER stress response
RNaseH HIV inhibition E2A/SCL aberrant gene expression
ABCG2 multi-drug transport RNAi/IGFR resistance to apoptosis
cKIT signal transduction Cripto 1 cell adhesion
HDAC/DNMT epigenetic control Polo-like kinase 1 cell cycle control
HIF-2? hypoxia response Smad 3 signal transduction
ER breast cancer cMet signal transduction
AP1 chemo-prevention Ezrin cytoskeletal reorganization
TRAIL apoptotic synergy
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Current Libraries for Screening
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NCIs Natural Products Collections and Extract
Repository
Terrestrial Plants -Tropical and
Subtropical Marine Invertebrates and
Algae -Indopacific -Caribbean Selected
Microbial Isolates -Cyanobacteria -Fungi gt
65,000 Organisms gt 170,000 Individual
Extracts -Organic Solvent Extracts -Aqueous
Extracts
Collections
Extract Repository
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