Tom Dunkley, Ph.D., During his Ph.D. work in the Dept. of Biochemistry at Cambridge University, Tom Dunkley developed a method that combined quantitative proteomics with subcellular fractionation to simultaneously localize hundreds of endogenous proteins to organelles. He then made the jump to industry with a post-doc at AstraZeneca near Manchester where he demonstrated that targeted MS could be used to quantify previously intractable pharmacodynamic biomarkers. Dunkley continued as a Senior Scientist at AZ using MS to answer oncology drug discovery questions on compound mechanism-of-action and target biology. In 2012, he switched companies and countries and joined Roche in Basel, Switzerland, as a Lab Head. At Roche, Dunkley lead a small lab applying targeted mass spectrometry to drug discovery projects across all Roche disease areas. Dunkley enjoys running and cycling and is trying to improve both his skiing and his German.

Targeted proteomics (and Skyline) to characterize an in vitro model of human neuronal development

Human pluripotent stem cell (hPSC)-derived cellular models have great potential to enable drug discovery and improve translation of preclinical insights to the clinic. To realize this potential, novel models must be validated in terms of both technical (reproducibility and robustness) and biological (relevance to physiological and disease processes) characteristics. A 246-protein (478 peptide, 2,868 transition) neuron-focused SRM approach has been developed and used to characterize a hPSC-derived model of human brain development across three key stages of in vitro neuron differentiation. Development of such a multiplexed SRM method, application to hundreds of samples and the resulting data analysis requires a sophisticated informatics platform. In this presentation I will demonstrate how Skyline and Panorama have facilitated development of multiplexed methods, streamlined data analysis and ultimately enabled application of SRM-based protein profiling to neuroscience drug discovery.