Akira Sawa, M.D., Ph.D.
Molecular dissection of cognition, emotion, and thought in conjunction with adolescent brain maturation: its application to clinical psychiatry
The research in our laboratory is directed towards understanding the pathogenesis of major mental illnesses, especially schizophrenia and mood disorders, at the molecular level. Furthermore, we anticipate our efforts may uncover fundamental mechanisms that mediate cognition, emotion, and thought. Taking advantage of our roles in both basic and clinical departments, our approach is interdisciplinary ranging from molecular cellular 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 these molecular targets are functionally related to each other within cells and neuronal networks of animal models, and how they contribute to disease phenotypes during a time course, especially in conjunction with adolescent brain maturation. Recently, we are concentrating on neuronal-glial functional interactions.
In a top-down approach, we study human subjects, including patients with major mental illness, through multifaceted approaches, including clinical assessments of psychiatry and psychology, brain imaging (MRI, MRS, and PET), and clinico-electrophysiological means (ERP, EEG, and TMS). In parallel, we conduct molecular dissection of biospecimens from these same sets of subjects. These biospecimens include olfactory neurons obtained via nasal biopsy, induced pluripotent stem cells and induced neurons, and other peripheral cells.
- Niwa, M., Jaaro-Peled, H., Tankou, S., Seshadri, S., Hikida, T., Matsumoto, Y., Cascella, N., Kano, S., Ozaki, N., Nabeshima, T., Sawa, A. (2013). Adolescent stress-induced epigenetic control of dopaminergic neurons via glucocorticoids. Science, 339, 335-339
- Kano, S., Colantuoni, C., Han, F., Zhou, Z., Yuan, Q., Wilson, A., Takayanagi, Y., Lee, Y., Rapoport, J., Eaton, W., Cascella, N., Ji, H., Goldman, D., and Sawa, A. (2012). Genome-wide profiling of multiple histone methylations in olfactory cells: further implications for cellular susceptibility to oxidative stress in schizophrenia. Mol Psychiatry, AOP
- Golzio C, Willer J, Talkowski ME, Oh EC, Taniguchi Y, Jacquemont S, Reymond A, Sun M, Sawa A, Gusella JF, Kamiya A, Beckmann JS, Katsanis N. (2012). KCTD13 is a major driver of mirrored neuroanatomical phenotypes of the 16p11.2 copy number variant. Nature 485, 363-367
- Ishizuka, K., Kamiya, A., Oh, E.C., Kanki, H., Seshadri, S., Robinson, J.F., Murdoch, H., Dunlop, A.J., Kubo, K., Furukori, K., Huang, B., Zeledon, M., Hayashi-Takagi, A., Okano, H., Nakajima, K., Houslay, M.D., Katsanis, N., and Sawa, A. (2011). DISC1-dependent switch from progenitor proliferation to migration in the developing cortex. Nature 473, 92-96
- Brandon, N.J., and Sawa, A. (2011). Linking neurodevelopmental and synaptic theories of mental illness through DISC1. Nat Rev Neurosci 12, 707-722
- Kondo, M., and Sawa, A. (2011). Anti-/Propsychotic drug signaling via heteromeric GPCRs--a balancing act? Cell 147, 964-965