Preclinical Efficacy and Safety Core

Brigham And Women'S Hospital, Boston MA

Investigators

Abstract

PROJECT SUMMARY/ABSTRACT PRECLINICAL EFFICACY AND SAFETY CORE The PRECISION-AD Preclinical Efficacy and Safety (PE&S) Core will serve three key functions: 1) optimize automated methods for scaling iPSC-derived 2D and 3D cultures to enable testing of interventions across genetic backgrounds; 2) implement automated assays to test candidate therapeutic interventions for AD across 100 genetic backgrounds; and 3) establish robust and efficient pipelines for sharing protocols and cellular models developed under this award. In order to accomplish these goals, the PE&S will work closely with the MPS Core to adapt their assays and protocols for automation. The work proposed under this core is made possible by NYSCF’s fully robotic platform (the NYSCF Global Stem Cell Array, GSCA)1 that automates iPSC derivation, differentiation, gene editing, high-content imaging, and drug screening to enable population-scale stem cell disease modeling and high-throughput drug discovery. Using this robotic platform, this core will scale both 2D and 3D microphysiological systems (MPS) to enable the testing of therapeutic interventions across 100 genetic backgrounds. Across these genetic backgrounds, the PE&S core will measure a panel of biomarkers identified by the BCB and MPS core that reflect responsiveness to each intervention tested. In addition, the core will establish and implement robust assays of cell health and cell type proportions using high throughput imaging and automated analysis pipelines. This core will develop rigorous best practices for testing of efficacy and toxicity in both 2D and 3D MPS and establish a core set of reporting standards and protocols for interrogating person- specific or subtype-specific responses to treatments. This work will be shared with the scientific community through efforts within the ADM Core including the development of online resources allowing the dissemination of protocols, data and cell line availability.