This Phase I SBIR project uses a new Quality Control microarray (QCarray) technology to generate Drug Toxicity Signatures (DTSs) for predicting liver toxicity in rat. The QCarray enables each element on every array to have a quality control (QC) score and markedly reduces a common source of error: fabrication of the cDNA microarrays. A second source of variability in arrays is genetic heterogeneity; therefore, we will benchmark the QCarray and look for DTSs using the PharmGenix Panel. The PharmGenix Panel models a heterozygous, variable genetic background in a controlled setting while reliably detecting drug toxicity. PhysioGenix will leverage archived tissues from previous PharmGenix drug studies and generate liver-specific DTSs to four different hepatotoxins. Matarray software will QC and normalize array data while principal component analysis will cluster expression patterns according to clinical chemistry, to help to determine informative DTSs. Phase II efforts will generate DTSs for toxicity to kidney and heart, and compare the liver DTSs to non-human primates. The common DTSs will be posited to be predictive biomarkers in the drug development process. Deliverables from this project will be of interest to the FDA and marketed to pharmaceutical companies for implementation into their existing drug development process.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
5R43CA106153-02
Application #
6931232
Study Section
Special Emphasis Panel (ZCA1-SRRB-U (M1))
Program Officer
Song, Min-Kyung H
Project Start
2004-08-01
Project End
2007-07-31
Budget Start
2005-08-01
Budget End
2007-07-31
Support Year
2
Fiscal Year
2005
Total Cost
$276,774
Indirect Cost
Name
Physiogenix, Inc.
Department
Type
DUNS #
140323531
City
Wauwatosa
State
WI
Country
United States
Zip Code
53226