The 21st Century Center of Excellence Program

The Project Leader's Profile

Masaya Tohyama (M.D., Ph.D.)
Dean, Professor , Department of Anatomy & Neuroscience, Osaka University Medical School/ Graduate School of Medicine

In 1972, graduated from the Osaka University School of Medicine and obtained M.D. After working as an intern, in 1977, obtained his PhD from Osaka University Medical School (Neuroanatomy). In 1980, appointed as Associate Professor in at the Department of Neuroanatomy, Institute of Higher Nervous Activity, Osaka University Medical School. In 1985, appointed as Professor and Chairman, Department of Anatomy & Neuroscience, Osaka University Medical School. In 1997, appointed as Professor and Chairman, Department of Anatomy & Neuroscience, Graduate School of Medicine, Osaka University. Since 1997, he holds the current position. Specialized in Molecular mechanism of neuronal death, regeneration of central nervous system and Schizopherenia. He has received following Awards; Beltz Prize in Japan (1991), JAPAN Bio Business Competition the most valuable Prize (2000), Highly Cited Researchers in Neuroscience by ISI (since 2001) etc.

Project Leader:	Masaya Tohyama, M.D., Ph.D., Dean, Professor, Department of Anatomy & Neuroscience, Osaka University Medical School/ Graduate School of Medicine
Research Members:	Yasutake Mori,M.D., Ph.D., Associate Professor, Department of Anatomy & Neuroscience, Osaka University Medical School/ Graduate School of Medicine
Research Collaborators:	Shingo Miyata, Ph.D., Assistant Professor, Department of Anatomy & Neuroscience, Osaka University Medical School/ Graduate School of Medicine Shinsuke Matsuzaki, M.D., Ph.D., Assistant Professor, Department of Anatomy & Neuroscience, Osaka University Medical School/ Graduate School of Medicine Tsuyoshi Hattori, M.D., Ph.D., Assistant Professor, The Osaka-Hamamatsu Joint Research Center For Child Mental Development Natsuko Kumamoto, M.D., Ph.D., Assistant Professor, Department of Anatomy & Neuroscience, Osaka University Medical School/ Graduate School of Medicine Tsuya Taneda, Ph.D., Post-doctoral fellow of the 21st Century COE Program, Department of Anatomy & Neuroscience, Osaka University Medical School/ Graduate School of Medicine Many others such as postdoctoral fellows, graduate students, and M.D./ Ph.D. course students of Department of Anatomy & Neuroscience, Osaka University Medical School/ Graduate School of Medicine

I)	Molecular Mechanism of Neuronal Disorders
1.	Recently, we reported that neuronal death occurring in neurodegenerative disorders(ND) such as Alzheimer's Disease(AD) etc. has its origin in the endoplasmic reticulum (ER). We focus on the mechanisms of organelle-specific cell death associated with several ND through promoting research into the response to the accumulation of aberrant proteins in organelle such as ER.
2.	Recently, Disrupted-In-Schizophrenia 1 (DISC1) was identified as a novel gene disrupted by a translocation that segregated with schizophrenia in a Scottish family. We identified some molecules as an interacting partner of the DISC1. We aim to elucidate the molecular mechanisms of schizophrenia onset through the analyses of the interactors.
II)	Molecular mechanisms regulating organellar function to protect cells against cellular stresses.
	Cells are exposed to various stresses under physiological and pathological circumstances. To protect cells against these stresses, defensive molecular systems are activated by transcriptional and translational regulations. Here we propose that these depend on not only the quantity changes but also quality changes of these molecules. In other words, the post-transcriptional and post-translational modifications are also important to resist stresses. Such modifications are regulated by the molecular mechanisms depending on organellar functions. We will reveal the organellar specific stress response mechanisms by identifying molecules that are involved in stress specific signal transductions. In addition, we will attempt to develop the therapeutic strategies for stress response related diseases, such as neurodegenerative disorder.
III)	Synapse response and protein synthesis
	Our aim is to elucidate molecular mechanisms which allow synapse-specific responses in different synapses located on the same neuron. Since the CNS neurons are supposed to accept different species of signals simultaneously at their different synapses, each synapse is likely to make a response to different stimuli from each of the presynaptic termini. One of the explanations for such locally separated signal response in the neuron is local protein synthesis by which appropriate amount and species of proteins are made from the localized mRNA in the synapses. We focus on the detailed mechanism which stabilizes mRNAs in the postsynaptic regions and regulates the expression of their corresponding proteins.

1)	Hattori T, Baba K, Matsuzaki S, Honda A, Miyoshi K, Inoue K, Taniguchi M, Hashimoto H, Shintani N, Baba A, Shimizu S, Yukioka F, Kumamoto N, Yamaguchi A, Tohyama M, and Katayama T. A novel DISC1-interacting partner DISC1-Binding Zinc-finger protein: implication in the modulation of DISC1-dependent neurite outgrowth. Mol. Psychiatry advance online publication, 2007.
2)	Okuda H, Manabe T, Yanagita T, Matsuzaki S, Bando Y, Katayama T, Wanaka A, and Tohyama M. Novel interaction between HMGA1a and StIP1 in murine terminally differentiated retina. Mol. Cell Neurosci., 33, 81-87, 2006.
3)	Ikenaka K, Miyata S, Mori Y, Koyama Y, Taneda T, Okuda H, Kousaka A, and Tohyama M. Immunohistochemical and western analyses of protein arginine N-methyltransferase 3 in the mouse brain. Neuroscience, 141, 1971-1982, 2006.
4)	Kumamoto N, Matsuzaki S, Inoue K, Hattori T, Shimizu S, Hashimoto R, Yamatodani A, Katayama T, and Tohyama M. Hyperactivation of midbrain dopaminergic system in schizophrenia could be attributed to the down-regulation of dysbindin. Biochem. Biophys. Res. Commun., 345, 904-909, 2006.
5)	Fujiwara T, Mori Y, Chu DL, Koyama Y, Miyata S, Tanaka H, Yachi K, Kubo T, Yoshikawa H, and Tohyama M. CARM1 regulates proliferation of PC12 cells by methylating HuD. Mol. Cell Biol., 26, 2273-2285, 2006.