Roles of lipid-regulating proteins in Alzheimer’s disease and other neurodegenerative diseases
We have demonstrated that lipid-regulating proteins, such as apolipoprotein E (ApoE), low-density lipoprotein receptor (LDLR), and ATP-binding cassette transporter 1 (ABCA1), regulate Abeta peptide aggregation and/or clearance. For example, ApoE gene haploinsufficiency in a mouse model of Abeta amyloidosis resulted in significant reduction in Abeta accumulation. In addition, overexpression of ApoE binding proteins, LDLR and ABCA1, in the brain markedly inhibited amyloid deposition and aberrant activation of glial cells. However, how apoE binding proteins affect Abeta clearance and aggregation is still unclear. We plan to investigate the potential role of them in the pathogenesis of Alzheimer’s disease at the molecular and cellular levels. In addition, we have identified two novel proteins that regulate LDLR trafficking and degradation. We plan to investigate the potential role of them in the pathogenic process of Alzheimer’s disease.
Role of microRNAs in neurodegenerative diseases and psychiatric disorders
MicroRNAs, small regulatory RNAs of ~22 nucleotides, are thought to have broad influence on gene expression by targeting mRNAs for degradation or translational repression. We are interested in identifying novel microRNAs that may play critical roles in neurodegenerative diseases or psychiatric disorders, by affecting lipid metabolism or synaptic plasticity. We integrate molecular and cellular biology approaches with systems biology methodology, such as transcriptomics and proteomics. In addition, we are interested in identification of microRNA-based biomarkers for neurodegenerative diseases.
Cellular modeling of brain aging and neurodegenerative diseases using iPS cells and trans-differentiated cells
With the emerging cell reprograming methods, such as differentiation of induced pluripotent stem (iPS) cells and direct trans-differentiation, we may be able to model human neurological diseases with more relevant human cell types. In addition, these technologies may allow us to screen drug candidates and test toxicity in a specific cell type of interest for a given disease. We are interested in validating the utility of reprogrammed cells to model neurodegenerative diseases and aging process.