Kasper Roet, PhD

17 Of 50 novel drugs approved by the F.D.A. between 1999 and 2008 came from target-based research, compared with 28 from “phenotypic” studies (Swinney 2013). The maturation of induced pluripotent stem technologies has made it possible to study disease related processes in relevant cell types derived from actual patients such as those suffering from Amyotrophic Lateral Sclerosis (ALS). This is also called "disease in a dish". Advancements in genome editing allow the correction of a disease causing mutation in these cells and thereby generate a negative control with an identical genetic background as the diseased line. These cells and their controls can now be used for phenotypic screens to identify compounds and their targets which can normalize a disease phenotype. I am leading the human induced pluripotent stem cell derived motor neuron project in the Woolf lab. Motor neurons derived from ALS patients exhibit an hyperexcitability phenotype compared to those derived from healthy controls. Motor neuron hyperexcitability has also been reported in ALS patients in many clinical studies. In collaboration with the Harvard Stem Cell Institute (Kevin Eggan lab) and GlaxoSmithKline we are developing high throughput ion-channel and chemogenomic compound screens using multi-electrode array and GCAMP6 analysis with these derived motor neurons to identify compounds and their molecular targets that can reduce the hyperexcitability of these neurons in ALS patients.