5You are surrounded by toxic lipidsSummary of ActivityWe have a lot of chances to contact with hazardous materials in our life. Particu-larly, toxic lipids can be continuously absorbed into the body, resulting in causing many kinds of diseases. For examples, excess level of cholesterol, fat containing high level of saturated fatty acid components, and trans-fatty acid enriched food containing margarine or shortening could induce harms in liver, heart, kidney, blood vessel and so on. Herbicide (2, 4-D) frequently used in irrigated rice field is known to cause abnormalities in testis and liver. Excess alcohol drinking could induce harms in brain, liver, blood vessel and so forth. The knowledge concern-ing these toxicity mechanisms might lead to the development of their preventive methods.・Elucidation of molecular mechanisms with diseases induced by various toxic lipids・Functional analysis of nuclear receptor (PPARα) using transgenic mice・Clarifying the pathogenesis of NASH, liver fibrosis and cancer, and metabolic syndrome・Evaluating the usefulness of naturally-derived functional foodsIt is important to understand toxicity of many kind of compounds in our environment. When we can fix category of their toxicity, for example; the level of abolishment such as smok-ing-related compounds, that of restriction on ingestion such as trans-fatty acids, and that re-quired to clarify the safety border such as cholesterol, it should be possible to construct safe and healthy circumstances.If you study these molecular mechanisms thoroughly, it is possible to find work in a variety of fields.Research subjectOutlook for researchOutlook for students after graduationMetabolic Regulationfive yearslaterLaparoscopy: a case of fast shift to cirrhosis in a NASH patientElectron microscopy of Leydig cells in mouse testis:disappearance of cholesterol particles through overproduction of testosterone in wild type mice fed with herbicide (2, 4-D) and appearance of them in PPARα–null mice fed with 2, 4-DClarication of the mechanism of diseases and development of novel therapies〜From generation to analysis of original gene-engineered mice〜Summary of ActivityIn Shinshu University, we are the only laboratory which can generate gene-engi-neered mice. We are developing novel technologies for genome editing (CRISPR/Cas9 method). For developing next-generation model of human diseases, we in-vented novel genome editing using maternal Cas9, which enables multiple gene modification at one time.We are studying various diseases (cancer, atherosclerosis, heart failure, diabe-tes, renal failure, cerebral infarction, liver cirrhosis and pulmonary fibrosis) and have international patents for drug discovery.・Clarification of the mechanism of disease and development of novel therapies using dis-ease model mice and cultured cells・Roles of vasoactive peptides in vascular development, angiogenesis and cancer metasta-sis・Generation and analysis of gene-engineered mice using CRISPR/Cas9 ・Regenerative medical research of heart, vasculature and liverEven by the modern medicine, there still do exist incurable diseases. Mission of medical researchers are to elucidate their causes and develop novel therapies. Our gene-engineered mice help us to execute the mission.Our PhD students learn various medical research skills in laboratory. After the graduation, they play leading roles as researches in universities and companies.Research subjectOutlook for researchOutlook for students after graduationCardiovascular Research（Chief: Professor Takayuki Shindo）Normal mouse (left) and obesity model mouse (ob/ob mouse) (right)LiverNormal mouseKnockout mouseLiver and kidney of normal mouse and endothelial cell-specific RAMP2 knockout mouseGenome editing using maternal Cas9 and platform of next-generation model of human diseasesNormal mouseKnockout mouseKidney
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