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Developing Standard and Universal Technologies essential for Drug Discovery

Numerous scientists at industrial and university laboratories are working tirelessly toward the development of novel pharmaceuticals, and we wish to utilize data from rapidly progressing basic sciences such as genomics and proteomics to develop technologies that are universally applicable in a wide array of pharmaceutical research and development areas.

Laboratory of Virology and Vaccinology

In addition to existing vaccines, the development of novel vaccines is desired to combat emerging and re-emerging infectious diseases. We carry out basic research for the development of new vaccines to suppress viral infections with an emphasis on research into characteristics of the herpesviruses and influenza virus.

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Laboratory of Adjuvant Innovation

Successful vaccines contain a component as an adjuvant that activates innate immune system, thereby eliciting antigen specific immune responses. Many of the adjuvant appeared to be a ligand for innate immune receptors such as Toll-like receptors (TLRs), RIG-I-like receptors (RLRs) and NOD-like receptors (NLRs), which are thus being a promising target to develop a novel adjuvant to elicit vaccine immunogenicity. Towards the optimal vaccine development, it is critical to understand how these innate immune receptor(s)-mediated innate immune activation by various adjuvants control their consequent adaptive immune responses to vaccine.

Our laboratory is to conduct functional and structural analysis of innate immune receptors and their interaction with the cognate ligand, which are often utilized as vaccine adjuvants. In addition, we continue to invent novel strategies and technologies to develop better and safer vaccines and their adjuvants. Our particular focus towards this goal is on elucidating the intra- and inter-cellular signaling pathways that mediate the immunogenicity of vaccines. By doing so, we hope to gain some senses not only for developing more efficient technologies for vaccines and adjuvants, but also ensuring their safety to higher level.

Background and Aims

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Laboratory of Stem Cell Regulation

Embryonic stem (ES) cells and induced pluripotent stem (iPS) cells show the characteristics of self-renewal and pluripotency. In our Lab, functional cells, such as hematopoietic cells, immune cells, hepatic cells, and renal cells, are efficiently differentiated from the stem cells. Our objectives are to establish the novel system of drug screening by using the differentiated cells.

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Laboratory of Toxicogenomics Informatics

Rapid progress in basic sciences related to genomics, proteomics and metabolomics (commonly called omics technology) has lead to advances in the implementation of omics technology in drug development. Since safety is always a major concern in drug development, ongoing our research is focused on toxicogenomics technology and actively conducted to develop new safety biomarkers. The toxicogenomics database used in our research was established by a collaborative project among National Institute of Biomedical Innovation (NIBIO), National Institute of Health Sciences (NIHS) and major Japanese pharmaceutical companies. The first 5-year project (2002-2007), named the Toxicogenomics Project(TGP1), established a large-scale, high-quality and well-designed toxicogenomics database comprising approximately 150 chemicals, mainly medical drugs. The second 5-year project (2007-2012), named the Toxicogenomics Informatics Project(TGP2), identified 30 and more potential safety biomarkers related to hepatotoxicity and nephrotoxicity, and demonstrated that toxicogenomics data combined with a large-scale integrated database were useful for assessing drug safety. To date, Our project (TGIP) are adding supplemental toxicogenomics data to the database, and also developing new safety biomarkers

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Laboratory of Immune Signal

Like hormones, cytokines are critical transmitters in intercellular signal transduction pathways. Abnormal signal transduction is known to cause a number of intractable diseases, including cancers, chronic inflammatory diseases, decreased immune protection against infections, and autoimmune diseases. In our laboratory, we are attempting to elucidate the roles of the regulatory family of supressor of cytokine signaling (SOCS) molecules in human diseases. This work should lead to the development of therapeutics for autoimmune diseases, cancers, life-style related diseases, and infectious diseases using SOCS molecules.

Laboratory of Immune Signal

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Laboratory of Biopharmaceutical Research

Recently, the number of clinically available biopharmaceuticals such as antibodies, cytokines, peptides is rapidly increasing. These biopharmaceuticals have caused a paradigm shift in disease treatment and has led to an improvement in the quality of life of patients with refractory cancers and autoimmune diseases. However, the technology for biopharmaceutical development is not well established. Indeed, an efficient technology for developing biopharmaceuticals is urgently required. In this regard, our project focuses on developing new technologies with a particular emphasis on the phage display system, which can generate a large repertoire of antibodies or mutant proteins. Our research project also includes proteomics-based studies for the identification of novel diagnostic markers and drug targets of refractory diseases. We are also interested in the development of novel drug delivery systems, such as nanotechnology-based devices or synthetic polymer-based devices, for controlling the in vivo behavior of biopharmaceuticals.

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Laboratory of Bioinformatics

We carry out structural and functional bioinformatics research into complex systems with the ultimate goal of developing novel drugs. Our work aims to extract new knowledge from large-scale experimental data, such as genome sequences and protein three-dimensional structures, particularly to aid target discovery. Our approaches include both algorithm development and analyses of individual biological systems.

Laboratory of Bioinformatics

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Laboratory of Cell Signal and Metabolism

Metabolic disorder is one of causes of intractable diseases, such as neuronal degenerative-disorders and hepatitis. We focused on molecular mechanisms of the cause and the exacerbation of these diseases, which identified some of proteins involved in the disorders.

Laboratory of Cell Signal and Metabolism

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Laboratory of Proteome Research

Many human diseases is caused by aberrant function of proteins. Therefore, it is obvious that development of novel biomarkers useful for diagnosis and treatment of the diseases needs to find such abnormal proteins. Proteomics is a powerful method to comprehensively analyze such proteins. Recent advances in proteomic technology made it possible to identify disease-related proteins in the clinical samples and thus extensive efforts are now attempted to search for the biomarkers across the country, however, none of them has been accepted for clinical use. The main reason is that candidate proteins for biomarker have not been evaluated if they are really involved in the development and progression of the diseases. In this project, our goal is to identify bona fide biomarkers useful for diagnosis and treatment of human diseases through functional analysis of candidate proteins by combining most recent proteomic technology with molecular and cellular biology.

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