The ability to mount a proper response to physiological and pathological stress is central to the maintenance of cellular homeostasis. This is particularly important to long-lived postmitotic cells such as neurons. It is well known that dysfunction of stress response underlies many neurological disorders including Alzheimer's and Parkinson's diseases. We direct our efforts to the understanding of the fundamental mechanisms of neuronal stress response with the following specific focuses:
1) Organelle network and neural stress: we are investigating signal transduction pathways that modulate and coordinate the stress response between multi subcellular organelles such as ER and lysosomes or mitochondria and ER. We are interested in determining the level, regulation, and role of such coordinated responses in neural cells;
2) MiRNA biogenesis and neural stress: we are investigating the mechanisms underlying how stress signals regulate the basic machinery of miRNA biogenesis. In this context, we are focusing on microprocessor, the nuclear complex that controls the initial steps of miRNA biogenesis and studying how Drosha is regulated by stress signals, how such a regulation modulates miRNA biogenesis, and whether dysfunction of Drosha occurs under pathological conditions;
3) Autophagy and neural stress: we are investigating the function and regulation of autophagy in cellular homeostasis and neurodegenerative diseases. We are particularly interested in the role of macro- and chaperone-mediated autophagy in neuroinflammatory process and how risk factors associated with AD and PD may modulate these autophagic processes;
4) Therapeutic targets and strategies: we want to validate potential new therapeutic targets and strategies for neurological diseases based on our discoveries. These efforts include validating the targets in relevant cellular and animal models, developing and testing approaches to modulate the targets, and evaluating their efficacy in altering the disease process.