• Aging and Neurodegeneration
• The current projects in our laboratory will use an integrated approach (i.e., combining molecular, cellular, biochemical, genetic and physiological techniques) by constructing in vitro and in vivo models to address the following critical issues:
(1) How does aging and disease-causing mutations provoke neurodegeneration?
(2) Why specific neuron types are more susceptible to these disease-causing mutations.
(3) How do different cell types, such as astrocytes and oligodendrocytes, contribute to disease progression?
Specifically, we will utilize different sets of transgenic mice expressing wild type and disease-linked mutations in human TDP-43, FUS/TLS and C9ORF72, including a novel model in which mouse TDP-43 is replaced with human gene. Furthermore, we will gain insight into molecular and cellular signatures of ALS-linked mutations in TDP-43, FUS/TLS and C9ORF72 with a genome-wide unbiased and quantitative approach to identify the protein and RNA interactors for these proteins.