The research in our laboratory is directed towards understanding the pathogenesis of neuropsychiatric illnesses, especially schizophrenia and neurodenerative disorders, at the molecular level.  Taking advantage of our roles in both basic and clinical departments, our approach is multi-faceted from molecular biology and animal models, to clinical studies using patient subjects: 

     In a bottom-up approach, we focus on concrete molecular targets, such as disease risk gene products and/or key cellular mediators.  We test how such molecular targets are functionally related with each other in cells and neuronal networks of animal models, and how they contribute to development of disease phenotypes during a time course. A recent study of ours indicates that schizophrenia-associated alteration of Disrupted-In-Schizophrenia (DISC1) lead to disturbance of proper development in cerebral cortex.  We are interested in how DISC1 and other risk gene products (neuregulin-1, dysbindin etc), together with environmental factors, including viral infections, functionally interact with each other, especially in neuronal migration, dendritic arbodization, and synaptic maturations, to form basic risks for schizophrenia.   Furthermore, we are studying how possible “disease pathways” involving DISC1 during neurodevelopment may contribute to schizophrenia-associated changes in young adulthood, such as aberrant neurotransmission and behavioral disturbance.

     In a top-down approach, clinical information and patient tissues are analyzed towards identifying novel molecular targets, or new biomarkers of disease.  Specifically, we are conducting biopsy of olfactory epithelium from schizophrenics and normal controls in order to characterize neuronal cells from patients.  In parallel, we perform systematic clinical and neuropsychological assessment and establish lymphoblastoid cells from peripheral blood.  By analyzing these tissues with microarray and proteomic approaches, we hope to identify novel and useful biomarkers for schizophrenia.