Accurately predicting cardiotoxicity and elucidating the underlying mechanisms remain vexing and expensive problems for drug discovery. This is due, in part, to the wide range of causes and manifestations. Ion-channel block can lead to acute and delayed arrhythmias, while biochemical toxicities can result in cell death, abnormal cardiac function, and even heart failure and death. Finding physiologically relevant, reproducible, and reliable cell models that can be used to detect these end points at preclinical and discovery stages has been a challenge, as most toxicity testing is done either by using immortalized cancer cell lines, primary explanted somatic cells, or live animals. The development of human induced pluripotent stem cell (iPSC)-derived cell lines as models for drug-toxicity testing offers a promising alternative that is more physiologically relevant, more predictive, and more time and cost efficient. Although iPSC-derived cardiomyocytes have not yet replaced well-established FDA-approved toxicological methods, the FDA has fast-tracked efforts...
As an attendee you will gain:
- A clear understanding of human induced pluripotent stem cell-derived cardiomyocytes
- The cardiotoxic effects of kinase inhibitors
- Cellular mechanisms of pro-arrhythmia
- The use of iPSC-derived cardiomyocytes in the accurate prediction and detection of cardiotoxicity and how they compare to other currently used models
Meet the Speakers:
Kate Harris, PhD, is a senior scientist in the Investigative Preclinical Toxicology group at GlaxoSmithKline. Harris earned her doctorate from the University of Sheffield, investigating calcium handling in normal and cystic fibrosis airway epithelia. She previously worked as a postdoctoral scientist for two years in GlaxoSmithKline’s Safety Pharmacology group, where her research focused on developing and validating an electrophysiology assay using human induced pluripotent stem cell-derived cardiomyocytes for cardiac safety screening.
Sarah Lamore, PhD, is a postdoctoral scientist at AstraZeneca Pharmaceuticals. Her current research focuses on utilizing cellular impedance measures of human iPSC-derived cardiomyocytes to deconvolute kinase inhibitor cardiotoxicity. She received her PhD in pharmacology and toxicology from the University of Arizona in 2012 for which she identified cysteine cathepsins as novel targets of UVA-induced photooxidative stress.