The DToxS Center seeks to obtain cellular signatures related to adverse effects caused by FDA approved drugs and the mitigation of these effects by coadministration of other drugs. Signatures are obtained from cell lines derived from individual human subjects, both primary cells, and cells derived from induced pluripotent stem cells. Cells are exposed, in culture, to single drugs and drug combinations, based on data obtained from adverse event reporting of clinically used drugs. Our focus is on drug-induced cardiotoxicity, hepatotoxicity and peripheral neuropathy
Zhao S, Nishimura T, Chen Y, Azeloglu EU, Gottesman O, Giannarelli C, Zafar MU, Benard L, Badimon JJ, Hajjar RJ, Goldfarb J, Iyengar R. Systems pharmacology of adverse event mitigation by drug combinations. Sci Transl Med. 2013 Oct 9;5(206):206ra140. doi: 10.1126/scitranslmed.3006548. PMID: 24107779
The overall goal of the Drug Toxicity Signature Generation Center (DTSGC) is to develop robust cellular signatures for drug-induced toxicity and toxicity mitigation. We build these signatures by exposing cells to drugs in culture, and integrating genomic and proteomic high-throughput measurements in multiple cell types with network analyses and simulations using dynamical models.