?Generation and analysis of gene-engineered mice using CRISPR/Cas9 ?Regenerative medical research of heart, vasculature and liverIn our laboratory, we are always actively discussing the relationship between glycans and gastric cancer. Human gastric cancer cell line.Mouse deficient in αGlcNAcNormal mouse (left) and obesity model mouse (ob/ob mouse) (right)LiverLiver and kidney of normal mouse and endothelial cell-specific RAMP2 knockout mouseto multiple genes発行：信州大学医学部From analysis of one gene Genome editing using maternal Cas9 and platform of next-generation model of human diseases Normal mouseKnockout mouse●No need of exogenous Cas9●Highly efficient genome editing●Low incidence of off-target and mosaic●High delivery of genome-edited newborns●Multiple genome editing at one time●Genome editinginadult miceNormal mouseKnockout mouseCRISPR/Cas9genome editing factorsDelivery systemCell, Organ, Individual levelKidney信州大学医学部医学科発行年月：２０２４年７月1Molecular PathologyCardiovascular research~From generation to analysis of original gene-engineered mice~ Understanding mechanism of gastric cancer development through glycobiologyClarification of the mechanism of diseases and development of novel therapiesGlycansareregardedasthethirdbiologicalchainsoffundamentalbiopolymers,thatcloselyassociatedwiththebiologicalphenomenasuchasdevelopment,immunity,infection,andcancer.Weinvestigatetheparticipationofglycansincausesofvariousdiseasesusingtechniquessuchasmorphology,molecularbiology,biochemistryandgeneticengineering.Recently,wedemonstratedthatαGlcNAcprotectsgastricmucosaagainstHelicobacterpylori(H.pylori)infectionandservesasatumorsuppressorfordifferentiated-typegastricadenocarcinoma.InShinshuUniversity,wearetheonlylaboratorywhichcangenerategene-engineeredmice.Wearedevelopingnoveltechnologiesforgenomeediting(CRISPR/Cas9method).Fordevelopingnext-generationmodelofhumandiseases,weinventednovelgenomeeditingusingmaternalCas9,whichenablesmultiplegenemodificationatonetime.Wearestudyingvariousdiseases(cancer,atherosclerosis,heartfailure,diabetes,livercirrhosisandpulmonaryfibrosis)andhaveinternationalpatentsfordrugdiscoveryrenalusing disease model mice and cultured cells?Roles of vasoactive peptides in vascular development, angiogenesis and cancer metastasisResearch subject* Functional analysis of glycans using genetically engineered mice. * Role of gastric gland mucin-specific O-glycans in preventing gastric cancer.* Investigation of various Helicobacterspecies in gastric diseases.Outlook for researchItmaybeusefulfornovelmoleculartherapiesanddiagnosesofcancerandinflammationthroughelucidationoffunctionsofglycansexpressedoncellsurfaceorsecretedfromcellsunderpathologicalconditions.Inaddition,anti-microbialdrugdesignexhibitingananti-microbialeffectonH.pyloricanbeprovided.H.pyloriresistanttoantibioticsbecometheproblemoferadicationcurrently.Outlook for students after graduationTobeglycobiologicalspecialistssuchasresearchersinuniversitiesorpublicinstitutes,privatelaboratories,orhospitals.Prof. Takayuki ShindoResearch subject?Clarification of the mechanism of disease and development of novel therapies Outlook for researchEvenbythemodernmedicine,therestilldoexistincurablediseases.Missionofmedicalresearchersaretoelucidatetheircausesanddevelopnoveltherapies.Ourgene-engineeredmicehelpustoexecutethemission.Outlook for students after graduationOurPhDstudentslearnvariousmedicalresearchskillsinlaboratory.Afterthegraduation,theyplayleadingrolesasresearchesinuniversitiesandcompanies.followedbynucleicacidsandproteins,thebiologicalfailure,cerebralinfarction,
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