Pharmacology aims to contribute to human welfare by clarifying interrelationships between drugs and human body. Our research interests are cellular molecules and functions of vascular endothelial cells and smooth muscle cells. Since these cells are closely related to the pathogenesis of hypertension, atherosclerosis, cancer metastasis and bronchial asthma, the changes in cellular molecules and functions are potential candidates of drug targets. We mainly use primary culture cells and analyze cellular functions and molecules from various aspects including protein expression, ion channels and gene expression. Furthermore, we perform in silico screening for drug development.

1.  Analysis of the regulation of local environments mediated by endothelium-derived substances, especially endothelium-related changes in tumor cell metastasis and vascular structure.
2. Novel pathogenesis of bronchial asthma by tracheal smooth muscle cells-derived proteases.
3. in silico drug development.

 

Our brain function emerges as network dynamics of 100 billion neurons. Our understanding of the brain circuit dynamics and its developmental mechanism not only contribute to better understanding of mental diseases, but also to our intellectual quest toward the origin of our mind. Our laboratory tries to understand logics of our brain from three different aspects: functional dynamics, circuit diagram, and its developmental process. We are studying cerebral cortex and olfactory bulb in mice to understand the molecular and circuit mechanisms of sensory circuit development. To facilitate our ongoing research on neuronal circuits, we are also trying to develop cutting-edge technologies for fluorescence microscopy-based connectomics.

1. Two-photon Ca²⁺ imaging of sensory information processing
2. Molecular and circuit mechanisms for sensory circuit development
3. Cortical circuit development in neuropsychiatric disease models
4. Circuit mechanisms of visceral (gut) sensation
5. Mathematical modeling of circuit dynamics for sensory perception
6. Development of new methodologies in connectomics

Developmental Cell 58:1221-1236 (2023); Cell Reports 35: 109276 (2021); Cell Reports 31:107814 (2020); eLife 7:e40350 (2018); Neuron 96:1139-1152 (2017); Cell Reports 14:2718-2732 (2016); Cell 154:1314-1325 (2013); Nature Neuroscience 16:1154-1161 (2013)

 

In our laboratory, we aim to elucidate the principles of life and drug discovery through dissecting the pathology of cardiovascular and respiratory diseases and COVID-19, focusing on RNA regulation and ACE2 signal transduction. Even now, when the molecular mechanisms underlying genome/epigenome regulation are being elucidated one after another, there are still many unclear points about the regulation of RNA metabolism and epitranscriptome in living organisms. Research of RNA metabolism / epitranscriptome is expected to lead to new modalities for drug discovery development, as in the case of corona mRNA vaccines. By utilizing disease biological approach with cutting-edge NGS technology, genetically modified mice and various disease models, we will analyze life phenomena and disease pathologies in a multifaceted and multi-hierarchical manner to understand pathological mechanisms and unknown life principles.

We will guide you in the research projects on the role of the RNA regulatory factor CCR4-NOT complex in cardiovascular and respiratory diseases, the regulatory mechanism of translational regulatory factors in malignant tumors, or the elucidation of the physiological role of Apelin-ACE2 system signal transduction.

We are investigating the molecular mechanisms, significance, and related diseases of large-scale and intriguing intracellular degradation phenomena occurring in vivo. So far, we have focused on the “phenomenon in which all organelles in the lens are degraded,” the mechanism of which had remained unknown for more than 100 years, and have succeeded for the first time in identifying a novel organelle degradation mechanism (mediated by PLAAT phospholipase) that does not involve autophagy (Morishita* [*co-principal author] et al., Nature 2021). We will continue to focus on the mysterious intracellular degradation phenomena occurring in various organs in vivo, while further expanding our vision, by making full use of molecular biology, cell biology, biochemistry, and other techniques, including zebrafish, mice, etc.

1. Elucidation of molecular mechanisms and physiological significance of large-scale intracellular degradation phenomena whose mechanisms are still unknown
2. Elucidation of molecular mechanisms and physiological significance of novel autophagy-independent intracellular degradation mechanisms
3. Elucidation of molecular mechanisms and physiological significance of selective autophagy

Mitochondria are important organelles that produce most of the ATP used by cells, and their abnormalities not only cause various diseases but are also closely related to aging. Our laboratory studies the molecular mechanisms and physiological functions of mitochondrial autophagy (mitophagy), a mechanism that maintains mitochondrial homeostasis by selectively degrading mitochondria. We aim to utilize mitophagy for the treatment of various diseases caused by mitochondrial abnormalities and for the inhibition of aging.

1. Experimental techniques for cellular and molecular biology
2. Methods for analysis of mitochondria and autophagy using mammalian cells, nematodes, and yeast
3. Disease phenotype analysis techniques using genetically engineered mice
4. Organelle morphology analysis techniques using fluorescence microscopy and electron microscopy