• Share
  • Email
  • Embed
  • Like
  • Save
  • Private Content
Mouse pharmacogenomics
 

Mouse pharmacogenomics

on

  • 1,917 views

 

Statistics

Views

Total Views
1,917
Views on SlideShare
1,916
Embed Views
1

Actions

Likes
1
Downloads
12
Comments
0

1 Embed 1

http://www.slideee.com 1

Accessibility

Categories

Upload Details

Uploaded via as Microsoft PowerPoint

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Processing…
Post Comment
Edit your comment

    Mouse pharmacogenomics Mouse pharmacogenomics Presentation Transcript

    • Towards systematic chemical genomics in mice and humans Chris Cotsapas PhD Daly Lab CHGR, MGH MPG, Broad [email_address]
    • The shoulders of giants
      • MGH
        • Mai Saito
        • Mari Mino-Kenudson
      • Broad/MPG
        • Mark Daly
        • David Altshuler
        • Supriya Gupta
        • Jennifer Moran
      • Broad/ChemBio
        • Stuart Schreiber
      • Broad/BMI
        • Vamsi Mootha
        • Joel Hirschhorn
      • Broad/NT
        • Robert Gould
      • MIT
        • Sangeeta Bhatia
        • Salman Khetani
        • Steve Katz
      • Broad/Cancer
        • David Thomas
        • Todd Golub
      • Broad/SPARC
        • Patrick Kleyn
    • The problem of drug toxicity
      • >2x 10 6 ADR hospitalizations in 30 years
      • Cost of millions
      • Drug development impediment
        • Vioxx, troglitazone etc etc etc
      • Genetic variation known
        • VKORC1, CYP2D6, CYP3A4, CYP3A5
      • Would be nice to know before unleashing on population!
    •  
    • Function of variation
      • Catalog of variation
        • HapMap
      • Lots of perturbations
        • screening libraries
      • Unified assay
        • HT, molecular... expression?
      • Lots of individuals
        • Tissue access
    •  
    •  
    • Questions
      • Can we use mice as a pharmacogenetic discovery tool?
        • Can we identify molecular signatures of response using inbred mice?
        • Are they heritable; can we map determinants?
      • Can we recapitulate live animal responses in vitro ?
      • Can we use surrogate tissues (blood)?
    • Liver and serum Drug Mouse inbred strain
    • Reagents
      • APAP
      • 5-FU
      • Rapamycin
      • Lovastatin
      • Cyclopamine
      • 129S1/SvImJ
      • A/J
      • AKR/J
      • BALB/cByJ
      • C3H/HcJ
      • C57Bl/6J
      • DBA/2J
      • NOD/LtJ
    • Specific Goals of Pilot
      • Phase I
        • Establish dosage levels for 5 drugs in one strain
        • Determine response variations
          • Serum biomarkers
          • Histology
          • Expression profiling
      • Phase II
        • Assay responses in 8 strains
          • Biomarkers, expression profiling, metabolite profiling
    •  
    •  
    •  
    • Specific Goals of Pilot
      • Phase I
        • Establish dosage levels for 5 drugs in one strain
        • Determine response variations
          • Serum biomarkers
          • Histology
          • Expression profiling
      • Phase II
        • Assay responses in 8 strains
          • Biomarkers, expression profiling, metabolite profiling
    •  
    • AST in congenic B6/A strains (Jax)‏
    •  
    •  
    •  
    •  
    •  
    •  
    • In progress...
      • Three further strain comparisons
      • Transcriptional and metabolic profiling
      • Peripheral blood profiling
      • in vitro hepatocyte assays
    •  
    •