Juntendo University, Tokyo, established in 1838.

Professor and Chairman：

Masato KOIKE, M.D., Ph,D.
e-mail: mkoike@juntendo.ac.jp
Tel: +81-3-5802-1024
Fax: +81-3-3830-8178

Professor：

Hiroyuki HIOKI, M.D., Ph,D.

Visiting Professor：

Bruno HUMBEL, Ph,D.

Assistant Professor：

Yu-Shin SODAKA, Ph,D.
Mutsumi YOKOTA, Ph,D.
Hiroshi KAMEDA, Ph,D.
Kenta YAMAUCHI, Ph,D.
Kazuki OKAMOTO, Ph,D.

Project Assistant Professor：

Kenichiro OKAMOTO, Ph,D.
Megumu TAKAHASHI, M.D., Ph,D.

Lecturer (Non-Full-time)：

Yoshiro TAKANO, D.D.S., Ph,D.
Takeshi SAKURAI, M.D., Ph,D.

Our research aims to understand how genetic mutations lead to cellular disorganization and disease, with special emphasis on neurodegenerative diseases related to autophagy, endo-lysosomes, and secretory pathways. Our research team integrates cell and molecular biology, biochemistry genetics, and light and electron microscopy.

1) Masato Koike (Professor and chairman)

We have been analyzing brain tissues from cathepsin D deficient mice, a model for the most severe type of neuronal ceroid lipofuscinoses (NCLs). NCLs are classified as rare inherited neurodegenerative diseases characterized with accumulation of mitochondrial proteins in lysosomes. However, taking into account that in many cases of early-onset familial Parkinson's disease (PD), genes essential for mitophagy are mutated, NCL and PD may share etiological features. Indeed, mutations in ATP13A2 gene are a known cause of Kufor-Rakeb syndrome (KRS) with both PD phenotypes and NCL pathology. We are going to continue genetic study of mouse models with impairment of autophagy and/or lysosomal proteolysis for better understanding of common neurodegenerative diseases.

2) Masato Koike (Professor and chairman)

Currently, the demand for the techniques bridging the gap between light and electron microscopy is expanding in the biomedical field. In collaboration with individuals at the Laboratory of Morphology and Image Analysis, one of the biggest and best equipped support facilities in Japanese medical schools, we are establishing more practical CLEM (correlative light and electron microscopy) method and applying 3D imaging of cells and tissues by focused ion beam/scanning electron microscopy (FIB/SEM). Furthermore, in collaboration with Prof. Klumperman, a chair of the department of cell biology and cell microscopy core, medical center Utrecht, where Prof. Koike was staying in 2014 as a visiting professor, we promote advanced Tokuyasu cryosectioning techniques for CLEM.

3) Hiroyuki HIOKI (Professor)

I have an interest in the neuronal circuitry in the central nervous system, especially in the neocortical microcircuit. Based on what principle, does the cerebral neocortex realize higher-order functions such as cognition, thinking, memory, and emotion? To unlock the mechanisms of the functions, it is absolutely essential to understand the neural network, which forms the structural basis of the brain. This is because “without structure there is no function”. I aim to unravel the grand design of the central nervous system, especially the neocortex, while developing innovative tools to facilitate morphological analysis.

4) Yu-Shin SODAKA (Assistant professor)

There are "acidic organelles" in the cell, such as the Golgi apparatus and endosomes/lysosomes, which maintain an acidic lumen. The acidic pH of the lumen is correlated with the morphology and function of organelles. This study focuses on the acidic pH of the Golgi apparatus in cells and tissues deficient in the Golgi-specific ion channel, Golgi pH regulator (GPHR), to elucidate the physiological role of luminal acidic pH maintenance. Clarification of the physiological role of Golgi luminal acidification will be applied to elucidate the pathological significance of the morphological abnormalities of the Golgi apparatus observed in various diseases.

5) Mutsumi YOKOTA (Assistant professor)

We are analyzing the function and morphology of mitochondria specific to dopaminergic neurons using tyrosine hydroxylase reporter iPSC lines to elucidate the mechanisms of dopaminergic neuron degeneration in Parkinson's disease.

6) Hiroshi KAMEDA (Assistant professor)

We have analyzed the neuronal network involved in the voluntary movement and sensory processing in the neocortex, striatum, thalamus and spinal cord using wild-type and disease model mice.

7) Kenta YAMAUCHI (Assistant professor)

We are interested in the structure of neural circuits and neural network dysfunction in neurodegenerative diseases. The human brain is organized over sizes that span several orders of magnitude, from the entire brain to synapses. We are thus currently working on developing a technique to visualize neural networks across multiple spatial scales for deciphering neural connectivity.

8) Kazuki OKAMOTO (Assistant professor)

I am a physiologist specializing in the study of synaptic connectivity and plasticity using patch-clamp techniques and in vivo extracellular recordings. During my PhD, I focused on the study of hippocampal circuits, especially the CA2 subregion. Currently, I am interested in understanding the learning system through the cholinergic network of the basal forebrain and brainstem.

• Sou, YS., Yamaguchi, J., Masuda, K., Uchiyama, Y., Maeda, Y., Koike, M. Golgi pH homeostasis stabilizes the lysosomal membrane through N-glycosylation of membrane proteins. Life Sci. Alliance 7(10): e202402677, 2024.
• Yokota, M. *, Yoshino, Y. *, Hosoi, M., Hashimoto, R., Kakuta, S., Shiga, T., Ishikawa K., Okano, H., Hattori, N., Akamatsu W., Koike, M. Reduced ER-mitochondrial contact sites and mitochondrial Ca2+ flux in PRKN-mutated patient tyrosine hydroxylase reporter iPSC lines. Front. Cell Dev. Biol. 11:1171440, 2023. (*These authors contributed equally to this work)
• Okamoto, K., Kamikubo, Y., Yamauchi, K., Okamoto, S., Takahashi, M., Ishida, Y., Koike, M., Ikegaya, Y., Sakurai, T., Hioki, H. Specific AAV2/PHP.eB-mediated gene transduction of CA2 pyramidal cells via injection into the lateral ventricle. Sci. Rep. 13(1):323, 2023.
• Takahashi, M., Kobayashi, T., Mizuma, H., Yamauchi, K., Okamoto S., Okamoto, K., Ishida, Y., Koike, M., Watanabe M., Isa, T., Hioki, H. Preferential arborization of dendrites and axons of parvalbumin- and somatostatin-positive GABAergic neurons within subregions of the mouse claustrum. Neurosci. Res. 190:92-106, 2023.
• Sou, YS., Yamaguchi, J., Kameda, H., Masuda, K., Maeda, Y., Uchiyama, Y., Koike, M. GPHR-mediated acidification of the Golgi lumen is essential for cholesterol biosynthesis in the brain. FEBS letters 596(22):2873-888, 2022.
• Yamauchi, K., Okamoto, S., Ishida, Y., Konno, K., Hoshino, K., Furuta, T., Takahashi, M., Koike, M., Isa, K., Watanabe, M., Isa, T., Hioki, H. Fluorochromized tyramide-glucose oxidase as a multiplex fluorescent tyramide signal amplification system for histochemical analysis. Sci. Rep. 12(1):14807, 2022.
• Yamauchi, K., Furuta, T., Okamoto, S., Takahashi, M., Koike, M., Hioki, H. Protocol for multi-scale light microscopy/electron microscopy neuronal imaging in a mouse brain tissue. STAR protocols i3(3):101508.
• Yamauchi, K., Okamoto, S., Takahashi, M., Koike, M., Furuta, T., Hioki, H. A tissue clearing method for neuronal imaging from mesoscopic to microscopic scales. JoVE (183), 2022.
• De Mazière, A., van der Beek, J., van Dijk, S., de Heus, C., Reggioli, F., Koike, M., Klumperman, J. An optimized protocol for immuno-electron microscopy of endogenous LC3. Autophagy 18(12):3004-22, 2022.
• Furuta, T.*, Yamauchi, K.*, Okamoto, S., Takahashi, M., Kakuta, S., Ishida, Y., Takenaka, A., Yoshida, A., Uchiyama, Y., Koike, M., Isa, K., Isa, T., Hioki, H. Multi-scale LM/EM neuronal imaging from brain to synapse with a tissue clearing method, ScaleSF. iScience 25(1):103601, 2021. (*These authors contributed equally to this work)
• Kitamura, E., Koike, M., Hirayama, T., Sunabori, T., Kameda, H., Hioki, H., Takeda, S., Itakura, A. Susceptibility of subregions of prefrontal cortex and corpus callosum to damage by high-dose oxytocin-induced labor in male neonatal mice. PLoS ONE 16(8):e0256693, 2021.
• Yokota, M., Kakuta, S., Shiga, T., Ishikawa, K., Okano, H., Hattori, N., Akamatsu W., Koike, M. Establishment of an in vitro model for analyzing mitochondrial ultrastructure in PRKN-mutated patient iPSC-derived dopaminergic neurons. Mol. Brain 14(1):58, 2021.
• Okamoto, S., Yamauchi, K., Sohn, J., Takahashi, M., Ishida, Y., Furuta, T., Koike, M., Fujiyama, F., Hioki, H. Exclusive labeling of direct and indirect pathway neurons in the mouse neostriatum by an adeno-associated virus vector with Cre/lox system. STAR protocols 2(1):100230, 2021.
• Parajuli, L.K., Koike, M. Three-dimensional structure of dendritic spines revealed by volume electron microscopy techniques. Front. Neuroanat. 5:627368, 2021.
• Parajuli, L.K., Urakubo H., Nakazato-Takahashi A., Ogelman, R., Iwasaki, H., Kwon, BH., Koike, M., Ishii, S., Oh, WC., Fukazawa, Y., Okabe, S. Geometry and the organizational principle of spine synapses along a dendrite. eNeuro 7(6), 2020. doi: 10.1523/ENEURO.0248-20.2020.
• Parajuli, L.K., Wako, K., Maruo, S,. Kakuta, S., Taguchi, T., Ikuno, M., Yamakado, H., Takahashi, R., Koike, M. Developmental changes in dendritic spine morphology in the striatum and their alteration in an A53T α-synuclein BAC transgenic mouse model of Parkinson's disease. eNeuro 7(4), 2020. doi: 10.1523/ENEURO.0072-20.2020
• Okamoto, S., Sohn, J., Tanaka, T., Takahashi, M., Ishida, Y., Yamauchi, K., Koike, M., Fujiyama, F., Hioki, H. Overlapping projections of neighboring direct and indirect pathway neurons to the external segment of the globus pallidus. iScience 23(9):101409, 2020.
• Parajuli, LK., Wako, K., Maruo, S., Kakuta, S., Koike, M. Unique synaptic topography of crest-type synapses in the interpeduncular nucleus. Biochem. Biophys. Res. Commun. 530(1):130-5, 2020.
• Sou, YS., Kakuta, S., Kamikubo, Y., Niisato, K., Sakurai, T., Parajuli, LK., Tanida, I., Saito, H., Suzuki, N., Sakimura, K., Maeda, Y., Kinoshita, T., Uchiyama, Y., Koike, M. Cerebellar neurodegeneration and neuronal circuit remodeling in Golgi pH regulator deficient mice. eNeuro 6(3), 2019. doi: 10.1523/ENEURO.0427-18.2019