Mentor: David K. Thomas, M.D., Cancer Program
Even after an investment of close to a billion dollars over more than a decade, about 10% of new compounds show adverse drug-host interactions. Although these situations can lead to a revised dosage regimen or a modified compound, more often the drug is pulled from the market by the F.D.A. or the pharmaceutical company. These harmful drug effects commonly result in toxicity in the blood, the cardiovascular system, or the liver.
Liver toxicity -- hepatotoxicity -- is an adverse drug reaction that accounts for approximately a third of withdrawals from the market. But testing drugs in development on animals can be expensive. Cell lines, on the other hand, lend themselves to high throughput screening and make excellent candidates for liver modeling. However, hepatocyte cell lines – liver cells -- are known to change dramatically after several days, limiting their use as models. Preliminary data suggest that drug metabolizing enzyme (DME) gene expression can be adjusted to reach levels characteristic of a fully functional liver, providing a potentially useful model.
"There are two words that describe my summer at the Broad Institute: access and experience. The access we were given, not only to the next generation in genomics tools and technology but also to the brilliant minds that compose the Broad, truly made for one of the most mentally stimulating summers I have ever had. I not only developed my critical-thinking and technical skills but also my communication and presentation expertise. The experiences I shared in the lab with my mentor as well as the time I spent with my colleagues will stay with me for the rest of my life. Genomics is the future of medicine and at the Broad you can be a part of it."
Peter Cruz-Gordillo, a neuroscience and biochemistry junior at Duke University, utilized HDACi to induce expression of drug metabolizing enzyme genes in liver cell lines with the goal of creating a more efficient and cost-effective human liver model for drug toxicity screening.