Charleen T. Chu, MD, PhD
Dr. Chu’s scientific interests center on altered cell signaling and neuronal cell biology in Parkinson's disease and related neurodegenerative disorders. As a practicing ophthalmic and neuropathologist, she integrates data from experimental models with human tissue studies. In particular, she focuses on biochemical mechanisms that interfere with effective neuroprotective adaptations to cellular stress, with an emphasis on mitochondrial homeostasis. She has discovered that mitochondrial oxidative stress and genetic factors intersect to disrupt the balance between autophagic degradation and biosynthetic responses needed to maintain neuronal health and functional neuritic/synaptic arbors. Her studies reveal a critical role for increased mitochondrial activation/trafficking and decreased nuclear transport of signaling proteins. She also discovered that neuronal autophagy is induced in multiple toxin and genetic models of parkinsonian neurodegeneration. Autophagy, the targeting of proteins/organelles for lysosomal degradation, is one of the most rapidly growing fields in biomedical research. Dr. Chu's work cuts to the heart of a controversy regarding the role of autophagy and mitophagy in neurodegeneration. While selective mitophagy is beneficial in removing abnormal mitochondria in recessive models of PTEN-induced kinase 1 (PINK1) deficiency, signaling mechanisms that result in overactivation of autophagy contribute to neurite retraction and cell death in other models (MPP+ and mutant LRRK2). Using phosphoproteomic and quantitative mass spectrometry, her group has been identifying novel phosphorylation sites on key kinase targets that regulate autophagic neurite retraction and synaptic dysfunction.