Biological Data Science
- Structural Biology
- Functional Genomics
- Genomic Function and Diversity
- Bio-informational Pharmacology
- Computational and Systems Biology
- Advanced Nanomedical Engineering
Most of the proteins only function when they adopt certain three dimensional structures; proteins which are chemically correct but structurally incorrect not only fail to function properly but also can harm cells. Our laboratory aims to understand the structure and function of biological macromolecules at atomic level, in the hope that accumulation of such knowledge help understanding diseases and will eventually lead to development of drugs. We use X-ray crystallography to determine the 3D structure of disease-related proteins and/or their complex with small molecules, and other methods of physical chemistry to elucidate their interactions. We are also involved in providing database of such structural data to scientists through the activities of Protein Data Bank Japan.
Our department "Functional Genomics" seeks to resolve how gene expression process is regulated in an individual. It does not simply mean "development". We set unique paradigms as follows;
Identification of regulatory factors of tissue-specific alternative mRNA splicing.
Manipulation of alternative mRNA splicing with newly developed chemical inhibitors of SR protein kinases.
Functional analysis of CREB in C. elegans.
In vitro analysis of RNP packaging with transcription/splicing coupling system.
Genomic Function and Diversity
Complex diseases such as immunological diseases, metabolic diseases and cancer diseases are caused by both genetic and environmental factors, with varying combinations in different individuals. Genome-wide association studies (GWAS) have led to the discovery of thousands of risk variants involved in these diseases, but the precise mechanisms of the diseases are not fully understood. Our laboratory aims to elucidate the disease etiology by dissecting the diversity of genomic function among individuals. To this end, we integrate bioinformatic approaches with molecular biology techniques in the analysis of genetic variants such as expression QTL and splicing QTL mapping. We will also establish to predict each individual’s pathophysiology (disease severity, drug response, etc.) based on the individual’s genome information to bring precision medicine into clinical practice.
This laboratory focuses on understanding fundamental physiological roles of ion channels and transporters in cardiovascular system. We employ multidisciplinary approach (patch-clamp, cell biology, optical recording, and proteomics) in order to seek novel regulatory mechanisms and modulatory molecules/compounds of ion channels and transporters in cardiac myocytes, vascular smooth muscle and endothelial cells, and circulating cells in vessels (leukocytes and lymphocytes). Our ultimate goal is to discover novel diagnostic and therapeutic strategy for intractable cardiovascular diseases, such as sudden death, life-threatening arrhythmias, and atherosclerosis, by modulating ion channels and transporters.
Computational and Systems Biology
We develop statistical models and information analysis methods to decipher vast amounts of biological information, based on cutting-edge data science and deep learning, and conduct medical research that contributes to the understanding of biological phenomena and diseases. We promote the fusion of mathematical science and medicine to elucidate the operating principles of living systems from the bottom up, based on omics information such as genome and gene expression and image information using state-of-the-art technology, and conduct research that will lead to medical innovations.
Advanced Nanomedical Engineering
Recent years have witnessed growing clinical approvals of new drug classes, including nucleic acid therapeutics, gene therapy, and mRNA vaccines, changing the concept of drugs. Focusing on mRNA vaccines and therapeutics, our laboratory develops nano-drug delivery systems (DDS) for these drugs to function appropriately in the patient’s body. Moreover, we apply them to disease treatment and attempt their clinical translation in collaboration with companies. Notably, our research interests include basic research for understanding biological processes we observe in application studies.