QT interval prolongation and arrhythmias have been a major cause for drug relabeling and withdrawals. However, only a small minority of patients exposed to culprit drugs develops the ADR, and the fundamental determinants of this individual sensitivity remain unexplained. In this project we will derive cardiomyocytes from individual patients whose drug-response phenotypes we have established. We will compare cells from those with drug induced long QT syndrome (diLQTS) to those who have been drug-tolerant both at baseline and with exposure to drugs known to elicit this ADR, including HERG blockers as well as those inhibiting PI3-kinase, a new pathway to diLQTS we have recently delineated.
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