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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.
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.
Laboratory of Immune Modulation
Development of innovative or more effective vaccines is social requirement as defenses to emerging- and re-emerging infectious diseases. For development of good vaccines, it is important not only to select best epitopes but also to find means to induce immune response effectively in appropriate fashion. Although compounds with such property, namely immune adjuvant, are already in use, much more effective and function-oriented adjuvant is needed.
There are many kinds of immune cells working as a complex network. To find target for function-oriented adjuvant, we need to understand roles and mechanisms of each immune cells. Thus we are focusing on two points as below.
1) Revealing regulatory mechanisms of immune system in cellular- and molecular levels.
2) Developing effective screening systems for compounds that modulate immune response using advanced tissue culture technologies.
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.
Laboratory of Toxicogenomics Informatics
We performed our first 5-year collaborative studies in the Toxicogenomics Project by the government and pharmaceutical companies in 2002 in which rats were exposed to chemicals (mainly medicines) and gene expression in liver (kidney in some cases) was measured by Affimetrix GeneChip and collected together with classical toxicological data. Experiments were also done with rat and human hepatocytes and more than 8 hundred million gene expressions for more than 150 chemicals were obtained by 2007. The data were combined with analysis and prediction systems established under the name of TG-GATEs (Genomics Assisted Toxicity Evaluation System). In order to utilize this system effectively, the second stage of the Toxicogenomics Informatics Project was started in 2007.
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 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.
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 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 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.