The long-term objective of my laboratory is to understand the early events of neural development. The primary goal is to discover the molecular-based mechanisms that initiate, develop and maintain the neuronal polarity and morphology in vitro and in vivo. We use primary hippocampal culture as an in vitro model in combination with genetic, biochemical, imaging and cell biological approaches for studying the early stages in neuronal development.
Our previous studies have demonstrated that BDNF, a secreted neurotrophin essential for the survival and differentiation of many neuronal populations, serves as a self-amplifying autocrine factor in promoting axon formation by triggering two nested positive-feedback mechanisms. We also discovered a new mechanism for E3 ubiquitin ligase Smurf1 to switch its substrate preference between two proteins of opposing actions on axon development.
In addition to chemical factors, physical supports imposed by the environment are also relevant for the axon/dendrite development. We have established a stiffness-tunable polyacrylamide hydrogel platform to study how neurons can coordinate the focal adhesion dynamics and membrane mechanics in order to adapt and grow on the extreme soft matrices, which enable neurogenesis and neuritogenesis.
We work on the axonal proteasome transport according to its traversing movement away or toward the growing neurite tips. We dissect the interaction between cytoskeletal motors and different proteasome complexes to understand by which form of proteasome, disassembled/assembled, 20S/26S, or posttranslationally modified, is it transported among neuronal compartments.