Current Research Projects:

1. Post-translational regulation of proteins in axonal growth and growth cone motility

Growth cones are highly motile structures found at the distal extremity of axons and are critically involved in formation of specific neuronal pathways, and thus in the correct …â œwiring during nervous system development. Growth cones are also responsible for target finding during repair. Growth cone motility depends on dynamic actin network and microtubule structures. The focus of this project is to understand the roles of local post-translational protein modifications, especially ubiquitination and phosphorylation, in regulation of actin and microtubule network.

2. Local protein synthesis in dendritic spine plasticity (Collaboration with Dr. Michel Baudry, USC)

Protein synthesis in dendritic spines is critically involved in memory stabilization/consolidation. Dendritic protein synthesis can be regulated by multiple factors. This project focuses on neurotrophic factor- and positive AMPA receptor modulator-induced dendritic protein synthesis in synaptic plasticity and spine morphogenesis, as well as the implication of these processes in learning and memory.

3. Autophagic/lysosomal dysfunction in Niemann-Pick Type C disease and Alzheimer s disease

Niemann-Pick Type C (NPC) disease is a rare and fatal neurovisceral storage disorder, which has neither treatment nor cure. NPC is generally caused by mutation in NCP1 and NPC2 genes, which encode proteins participating in intracellular cholesterol transport. The pathological hallmark of NPC is accumulation of cholesterol and other lipids in the endosomal-lysosomal systems. Neurodegeneration is a common feature of the disease, and in most cases, is the final cause of death. The mechanisms underlying neurodegeneration are currently unknown; however, accumulating evidence indicates that NPC may share some common pathological mechanisms with Alzheimer's disease (AD). We have found that both diseases have abnormal autophagic activity and lysosomal dysfunction. Both diseases show neurofibrillary tangles and inflammation. Research from our lab as well as others has revealed that treatment with the neurosteroid allopregnanolone can reduce cholesterol accumulation and extend lifespan of NPC mice. Current research on this project focuses on further understanding of how interruption of cholesterol homeostasis leads to neuronal death and on developing strategies to promote NPC neuronal survival. Since NPC and AD share common features neuropathology, we hope our research can also lead to better therapy for AD.