Tong Wang, PhDAssistant Professor

In mammalian central nervous system (CNS), neurons are the basic functional unit for information processing. The long and thin neuronal axon segment serves as both the ‘cable’ for electrical signal transduction and the ‘high-speed railway’ for material exchange. The specialized axonal cytoskeleton facilitates the efficient long-range cargo transport and maintains the structural stability of these thin axons, which are critical for CNS function. Consistently, progressive degeneration of axons have been extensively noticed in traumatic brain injury (TBI) and neurodegenerative disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD) and motoneuron diseases (NMD) and serves as the earliest sign or the causing reason of these pathologies. However, how this vulnerability of axons is encoded in the molecular and cellular levels, and how they are triggered by genetic or mechanical factors remain elusive. This is largely due to the small caliber of CNS axons (<0.5 μm) and the dynamic movements of various types of axonal carriers, these factors make it very challenging to study how the axonal cytoskeleton and active cargo trafficking are coordinate underlying multiple physiological and pathological processes. With the recent advances in microscopy techniques and development of in vitro microfluidic assays, which separate axons from the rest of the neuronal parts, many of the previously unattainable coordination could be unraveled. We therefore aim to investigate the coordination between the axonal structure and cargo trafficking underlying the following critical functional and pathological procedures:

1) Establish the microfluid-based in vitro platform to study the underlying mechanisms of diffusive axonal injury. 2) Explore the role of long-range axonal trafficking in the process of neuronal injury and degeneration. 3) Define the functional and regulatory pathways of the periodic axonal cytoskeleton in diffusive axonal injury and degeneration. (4) Combinedly use the microfluid techniques and computational simulation to screen for the factors promote axonal regeneration.

The ultimate goal of our research is to find ways to rescue and revert the impaired subcellular changes in the axon that leads to the severe damages in many forms of neurodegenerative diseases and neural injury.