The ultimate goal of our research is to understand the molecular mechanisms of mental disorders, such as schizophrenia and other associated neuropsychiatric conditions, which may eventually lead to new therapeutic strategies. During the last decade, there has been significant progress in determining the mechanisms whereby many genetic risk factors impact brain development. Nonetheless, given that the majority of psychiatric disorders have etiological complexities encompassing multiple risk genes and environmental factors, the biological mechanisms of these diseases remain poorly understood.
By employing a multidisciplinary approach, such as genetics, biochemistry, molecular biology, and conditional gene targeting, including in utero electroporation, a technique for spatial and temporal manipulation of multiple risk genes, our laboratory is able to advance understanding of disease mechanisms. We investigate how genetic risk factors during brain development may influence neuronal circuit maturation and resultant behaviors, with a focus on prefrontal cortex development and function.
Kamiya, A., Kubo, K., Tomoda, T., Takaki, M., Youn, R., Ozeki, Y., Sawamura, N., Park, U., Kudo, O., Okawa, M., Ross, C.A., Hatten, M.E., Nakajima, K., Sawa, A.: Disrupted-in-Schizophrenia-1 is required for neuronal migration in the cerebral cortex: perturbation by schizophrenia-associated mutation. Nature Cell Biol., 7; 1167-1178 (2005) (highlighted as “ 10 major breakthroughs in 2005 in Science 310: 1880-1885 2005”)
Kamiya, A., Tomoda, T., Chang, J., Takaki, M., Zhan, C., Morita, M., Cascio, M.B., Elashvili, S., Koizumi, H., Takanezawa, Y., Dickerson, F., Yolken, R., Arai, H., Sawa, A.: DISC1-NDEL1/NUDEL protein interaction, an essential component for neurite outgrowth, is modulated by genetic variations of DISC1. Hum. Mol. Genet. 15; 3313-3323 (2006)
Kamiya, A., Tan, P.L., Kubo, K., Engelhard, C., Ishizuka, K., Kubo, A., Tsukita, S., Pulver, A. E., Nakajima, K., Cascella, N. G., Katsanis, N., Sawa, A.: PCM1 is recruited to the centrosome by the cooperative action of DISC1 and BBS4 and is a candidate for psychiatric illness. Arch. Gen. Psychiatry 65; 996-1006 (2008)
Niwa, M.*, Kamiya, A*., Murai, R., Kubo, K., Gruber, A., Lu, L., Seshadri, S., Hiyama, H., Jaaro-Peled, H., Noda, Y., Cascella, N., O’donnell, P., Nakajima, K., Sawa, A., Nabeshima, T.: Transient knockdown of DISC1 in the developing cerebral cortex leads to dopaminergic disturbance and schizophrenia deficits in young adult mice. *These authors contributed equally to this work. Neuron 65; 480-489 (2010)
Zoubovsky, SP, Pogorelov, VM, Taniguchi, Y, Kim, S, Yoon, P, Nwulia, E, Sawa, A, Pletnikov, MV, Kamiya, A.: Working memory deficits in neuronal nitric oxide synthase knockout mice: potential impairments in prefrontal cortex mediated cognitive function. Biochem Biophys Res Commun 408; 707-712 (2011).
Taniguchi, Y, Young-Pearse, T, Sawa, A, Kamiya, A.: In utero electroporation as a tool for genetic manipulation in vivo in order to study psychiatric disorders: from genes to circuits and behaviors. Neuroscientist 2011 May 5 [Epub ahead of print].