TFRI-OICR Selective Therapies - Target Identification Program



Period from:2008-04-01 to 2009-06-30
Principal Investigators:Dr. Rob Rottapel
Co-Investigators:David Andrews; Eric Brown; Troy Ketela; Jason Moffat; Aaron Schmimmer; Ben Neel; Eric LaCasse; Bob Korneluk; Robert Screaton; David Stodjl; Dan Durocher; Bradley Wouters; Racq Hakem; Martin Holcik; John Dick; David Kaplan; Peter Dirks; John Hassell; Eldad Zacksenhaus; Jeff Wrana; Liliana Attisano; Rod Bremner; Tony Pawson
Institution:Ontario Institute of Cancer Research
Partner:Ontario Institute of Cancer Research
Program:Pilot Research Project
Abstract: The overall objective of this program is to identify new cancer targets for which novel and selective anti-cancer therapeutics can be developed.

Novel cancer targets will be identified using high throughput RNA interference (RNAi) screening technologies and cross-validated with independent RNAi methods (shRNA or esiRNA). Targets will be further assessed for biological function in animal models, and for anti-cancer activity in relevant in vivo cancer models. Validated targets will be subjected to high throughput screening (HTS) of diverse chemical libraries to identify first-generation small molecules that specifically and selectively sensitize tumours to death or involution. These "hits" will be optimized through medicinal chemistry efforts, and a drug discovery platform will be created.

The program comprises a fully integrated team of clinician scientists, molecular biologists, pharmacologists and medicinal chemists that supports activities across four screening platforms and four thematic research areas. In the first year, the Seed Fund is being used to build infrastructure at screening facilities across Ontario, ensuring adequate capacity to meet the needs of all program researchers in the next five years.

Screening Platforms: The program will capitalize on the screening expertise at four facilities across Ontario:
  1. McMaster HTS Lab, McMaster University, Hamilton
  2. McMaster Biophotonics Facility, McMaster University, Hamilton
  3. SMART Facility, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto
  4. The COLT Facility, Centre for Cellular and Biomolecular Research, University of Toronto, Toronto
These facilities offer technical expertise in assay development and validation, data management and analysis, access to different RNAi technologies, and access to sophisticated HTS robotic capabilities.

Research Clusters: Initially, the program will focus its target discovery activities in four principal thematic research areas, as outlined below:
  1. Apoptosis
  2. DNA Damage and Stress Response in Cancer
  3. Cancer Stem Cell
  4. Morphogenesis and Tissue Homeostasis in Cancer
Funding Information:
2008-2009$692,850
2009-2010$16,962
TOTAL$709,812

 
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