Guilian Xu,

My work is trying to find the underlying mechanisms of age-related brain disorders, such as Alzheimer’s disease (AD), Huntington disease (HD), Parkinson’s disease (PD) and motor neuron diseases (ALS). HD only has a familial form, while AD, PD, and ALS have both familial forms inherited from parents and sporadic forms that do not have a clear family link. Geneticists have discovered the genes that cause these diseases, and we make genetically engineered mice that modify those genes to model the conditions according to their findings. In most cases, the mice show the same symptoms as the patients. It is extremely beneficial to study the mechanisms and try therapies on the disease models of mice before translating into patients.

All these disorders seem to share similar common mechanisms of pathogenesis, although for now, no single common mechanism has yet emerged. All these diseases have insoluble protein accumulation involved and the major aggregated proteins are transmissible. I am testing a hypothesis called “secondary misfolding” by protein homeostasis damage which states: if a high level of one protein (usually with disease favored mutations) starts to lose its solubility and accumulates inside the cells, it can destroy the balance of other protein production, maintenance, and clearance. This process triggers the dysfunction of many independent biological pathways simultaneously and eventually kills the cells. This work involves the use of transgenic mouse models, human tissues, and cell culture systems to examine the soluble, insoluble proteins and their relationship with some bioinformatics tools.

• ALS
• Alzheimer’s Disease
• Neuropathology of Neurodegenerative diseases