Leslie N. Aldrich, PhD,  Stadtman Investigator, Chemical Biology Section, Molecular Targets Program, National Cancer Institute, Frederick, MD

“Phenotypic and targeted approaches to discover novel autophagy modulators for therapeutic development”
Autophagy, an evolutionarily conserved catabolic process in which cytosolic content is engulfed, degraded in lysosomes, and recycled, has emerged as a promising pathway for therapeutic modulation to impact numerous human diseases. Our group has implemented both target-based and phenotypic high-throughput assays to discover novel autophagy modulators and to study the role of this pathway in cancer and neurodegenerative diseases, including the lysosomal storage disease, Niemann-Pick Type C (NPC), and Alzheimer’s Disease. In this talk, I will describe our efforts to discover small molecules that disrupt protein-protein interactions to selectively inhibit autophagy and our progress towards determining the mechanisms of small-molecule autophagy modulators that show promising activity in cell-based disease models.