Peroxisome biogenesis disorders (PBDs)

National Center For Advancing Translational Sciences

Investigators

Abstract

In collaboration with J. Hacia (USC), N. Braverman (McGill University), and postdoctoral support by the Global Foundation for Peroxisome Disorders (GFPD) and the Wynne Mateffy Foundation the ADST laboratory of NCATS has optimized a 1536-well plate format high content automated microscopy-based imaging assay for the identification of phenotype-perturbing substances from NCATS chemical libraries. Initial work on this project has included quantitative HCS with libraries of bioactive chemical probes and approved drugs, as well as gene silencing libraries to discover and map pathways that have the potential to mitigate peroxisome biogenesis disfunction. Compounds and genes identified in these initial screens are currently being tested for activity in a series of biological validation assays in the Hacia lab at USC to substantiate that the phenotypic response observed in the HCS assay is reflective of an effect on peroxisome biogenesis. In addition, transgenic mouse models with various PBD mutations are being developed in the Braverman lab at McGill University as models for both peripheral and CNS phenotypes of the disease.