We are interested in the genetic basis of drug induced cardiotoxicity, and how these genetic factors may underlie serious adverse drug reactions that affect a small but significant fraction of individuals, therapeutic circumstances, o both. We will conduct genomewide screens for factors affecting cardiomyocyte contractile deficit or arrhythmia caused by anthracycline and tyrosine kinase inhibitor induced contractile deficit or arrhythmia. The ultimate research goal of this project is to discover novel mechanisms, targets, and chemical structures underlying variability in drug induced cardiotoxicity. The proposed two-stage approach is to first conduct high throughput genomewide association studies in vitro using genetically diverse mouse ES derived cardiomyocytes. The genes found in those studies will be functionally validated in human IPS derived cardiomyocytes by reducing their expression via gene knockdown. This approach takes advantage of the mapping power of mouse genetics with the biological relevance of human cell responses.

Public Health Relevance

We are developing a high throughput platform for understanding how genes and drugs can interact to damage the heart. This research will ultimately improve treatment of many diseases by reducing the likelihood of unexpected drug induced heart damage.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
1R44ES025139-01A1
Application #
8714197
Study Section
Special Emphasis Panel (ZRG1-CVRS-C (10))
Program Officer
Shaughnessy, Daniel
Project Start
2014-08-01
Project End
2015-01-31
Budget Start
2014-08-01
Budget End
2015-01-31
Support Year
1
Fiscal Year
2014
Total Cost
$199,127
Indirect Cost
Name
Predictive Biology
Department
Type
DUNS #
144728818
City
Carlsbad
State
CA
Country
United States
Zip Code
92011