Yasuko Iwakiri, PhD
Cards
Appointments
Education
Colorado State University (2000)
Contact Info
Yale School of Medicine
Department of Medicine (Digestive Diseases), PO Box 208019
New Haven, CT 06520-8019
United States
Appointments
Education
Colorado State University (2000)
Contact Info
Yale School of Medicine
Department of Medicine (Digestive Diseases), PO Box 208019
New Haven, CT 06520-8019
United States
Appointments
Education
Colorado State University (2000)
Contact Info
Yale School of Medicine
Department of Medicine (Digestive Diseases), PO Box 208019
New Haven, CT 06520-8019
United States
About
Titles
Professor of Medicine (Digestive Diseases)
Appointments
Digestive Diseases
ProfessorPrimary
Other Departments & Organizations
Education & Training
- PhD
- Colorado State University (2000)
Research
Overview
Vascular biology of the liver:
My lab has been committed to working on the lymphatic system in the liver, which is a very unexplored area in the study of liver biology (Chung & Iwakiri, CMH, 2013; Iwakiri, Hepatology, 2016; Tanaka & Iwakiri, CMGH, 2016).
Liver fibrosis:
- We investigate the role of each major liver cell type in fibrogenesis with a particular interest in hepatic stellate cells (HSC), a cell type that has the most direct impact on the development of fibrosis. We have determined that a protein called Reticulon 4B (a.k.a., Nogo-B) increases fibrosis by promoting collagen production by HSCs (Zhang et al., Hepatology, 2011) and protecting HSCs from apoptosis (Tashiro et al., Am J Pathol, 2013).
- In collaboration with Dr. Mark Saltzman (Yale University), we have explored the therapeutic potential of targeting Reticulon 4B in HSCs for liver fibrosis by delivering siRNA encapsulated in nanoparticles. While nanoparticles have been considered an important tool for delivery of drugs and the liver has been known to retain nanoparticles, their cellular distribution in the liver was not clearly understood. We conducted extensive analyses of liver cell uptake of nanoparticles and demonstrated their cellular distribution in vivo for the first time (Park et al., Nanomedicine, 2016). This study is significant since the effectiveness and safety of medical application of nanoparticles for liver therapy depends on their specific delivery to targeted cell populations.
Kupffer cells/macrophages in the pathogenesis of alcohol-induced liver disease:
Alcohol abuse causes liver disease, whose spectrum includes alcoholic fatty liver, alcoholic hepatitis, fibrosis, cirrhosis and hepatocellular carcinoma in a progressive manner. Early intervention may prevent progression to cirrhosis and hepatocellular carcinoma, but effective treatments are limited due to our incomplete understanding of the molecular and cellular mechanisms of alcohol-induced liver injury. My lab studies the mechanism of alcohol-induced liver injury, in which Kupffer cells (liver resident macrophages) have a pivotal role. We also explore therapeutic potential of nanoparticle delivery to Kupffer cells for the treatment of alcoholic liver disease.
Medical Subject Headings (MeSH)
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
William Sessa, PhD
Matthew McConnell, MD
Derek Toomre, PhD
Xinshou Ouyang, PhD
Anton Bennett, PhD
Arumugam Suyavaran, MSc, PhD
Hypertension, Portal
Endothelial Cells
Kupffer Cells
Fibrosis
Lymphangiogenesis
Liver Regeneration
Publications
2024
Selective inhibition of tumor microvascular permeability by cavtratin blocks tumor progression in mice
Gratton J, Lin M, Yu J, Weiss E, Jiang Z, Fairchild T, Iwakiri Y, Groszmann R, Claffey K, Cheng Y, Sessa W. Selective inhibition of tumor microvascular permeability by cavtratin blocks tumor progression in mice. Cancer Cell 2024, 42: 1127. PMID: 38821059, DOI: 10.1016/j.ccell.2024.05.009.Peer-Reviewed Original ResearchUnlocking the Role of Liver Sinusoidal Endothelial Cells: Key Players in Liver Fibrosis
Iwakiri Y. Unlocking the Role of Liver Sinusoidal Endothelial Cells: Key Players in Liver Fibrosis. Clinical And Molecular Hepatology 2024 PMID: 38726502, DOI: 10.3350/cmh.2024.0343.Peer-Reviewed Original ResearchInterleukin-7-based identification of liver lymphatic endothelial cells reveals their unique structural features
Yang Y, Jeong J, Su T, Lai S, Zhang P, Garcia-Milian R, Graham M, Liu X, McConnell M, Utsumi T, Pereira J, Iwakiri Y. Interleukin-7-based identification of liver lymphatic endothelial cells reveals their unique structural features. JHEP Reports 2024, 6: 101069. PMID: 38966234, PMCID: PMC11222939, DOI: 10.1016/j.jhepr.2024.101069.Peer-Reviewed Original ResearchAltmetricConceptsCell surface structuresLymphatic endothelial cellsPublished single-cell RNA-sequencingRNA-seq analysisScRNA-seq analysisSingle-cell RNA sequencingLymphatic systemEndothelial cellsInterleukin-7RNA-seqScRNA-seqExpressed genesRNA sequencingTranscriptomic changesLow abundanceI/R liver injuryGenesIsolation protocolLiver cell typesCell typesIsolation methodLiver of miceHuman liver specimensHeterozygous miceMouse liverChapter 13 Liver Sinusoidal Cells in alcohol-associated liver disease
Iwakiri Y. Chapter 13 Liver Sinusoidal Cells in alcohol-associated liver disease. 2024, 285-291. DOI: 10.1016/b978-0-323-95262-0.00013-9.Peer-Reviewed Original ResearchConceptsAlcohol-associated liver diseaseLiver sinusoidal endothelial cellsPathogenesis of alcohol-associated liver diseaseChronic alcohol consumptionSinusoidal endothelial cellsLiver diseaseNormal function of immune cellsEndothelial cellsFunction of immune cellsSinusoidal cellsAlcohol consumptionIntrahepatic vascular toneHepatic stellate cellsEndothelial cell populationLiver sinusoidal cellsLiver cell typesImmune cellsAntigen clearanceVascular toneKupffer cells/macrophagesKupffer cellsStellate cellsCell populationsLiver homeostasisLiver
2023
Berberine protects mice against type 2 diabetes by promoting PPARγ-FGF21-GLUT2-regulated insulin sensitivity and glucose/lipid homeostasis
Chen Y, Li Q, Zhao S, Sun L, Yin Z, Wang X, Li X, Iwakiri Y, Han J, Duan Y. Berberine protects mice against type 2 diabetes by promoting PPARγ-FGF21-GLUT2-regulated insulin sensitivity and glucose/lipid homeostasis. Biochemical Pharmacology 2023, 218: 115928. PMID: 37979703, DOI: 10.1016/j.bcp.2023.115928.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsType 2 diabetesInsulin sensitivityGlucose/lipid homeostasisInsulin resistanceLipid metabolismFibroblast growth factor 21Glucose/lipid metabolismFGF21-dependent mannerGlucose transporter 2 expressionLipid homeostasisGrowth factor 21Liver lipid accumulationMechanism of berberineEffects of berberineRole of berberineTransporter 2 expressionExpression of PPARγGlobal knockout miceFunction of berberineMultiple therapeutic actionsRegulation of glucoseT2D treatmentT2D miceDiabetic miceCarcinoma cell linesPortal Hypertension in Alcohol-Associated Hepatitis
McConnell M, Iwakiri Y. Portal Hypertension in Alcohol-Associated Hepatitis. Current Hepatology Reports 2023, 22: 67-73. PMID: 37214274, PMCID: PMC10075503, DOI: 10.1007/s11901-023-00601-y.Peer-Reviewed Original ResearchCitationsConceptsAlcoholic hepatitisPortal hypertensionMajor public health problemAlcohol‐Associated HepatitisLiver-related morbidityPublic health problemReviewThis review articleIntrahepatic vasoconstrictionHospital admissionPortal inflowPerisinusoidal fibrosisHypertensionHealth problemsLiver vasculatureHepatitisClinical perspectiveMultiple possible mechanismsReview articlePossible mechanismPhlebosclerosisVasoconstrictionMorbidityInflammationAdmissionFibrosisOverexpression of NgBR inhibits high-fat diet–induced atherosclerosis in ApoE-deficiency mice
Gong K, Wang M, Wang D, Gao Y, Ma L, Yang X, Zhu X, Chen S, Zhang M, Li H, Chen Y, Hu W, Miao Q, Iwakiri Y, Liao C, Duan Y, Han J. Overexpression of NgBR inhibits high-fat diet–induced atherosclerosis in ApoE-deficiency mice. Hepatology Communications 2023, 7: e0048. PMID: 36996002, PMCID: PMC10069848, DOI: 10.1097/hc9.0000000000000048.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsNgBR overexpressionScavenger receptor type BIHigh-fat diet-induced atherosclerosisApolipoprotein E deficient miceApoE deficiency miceApoE-/- miceDiet-induced atherosclerosisHigh-fat dietLevels of cholesterolBile acid synthesisCholesterol synthesis genesInflammatory factorsVascular inflammationProtein kinase αSinus lesionsHepatic steatosisAortic rootRisk factorsDeficient miceAtherosclerosis treatmentFree fatty acidsCholesterol metabolismAtherosclerosisAcid synthesisAAV injectionLymphatics in the liver for translational science
Iwakiri Y. Lymphatics in the liver for translational science. Clinical Liver Disease 2023, 21: 122-124. PMID: 37936952, PMCID: PMC10627586, DOI: 10.1097/cld.0000000000000019.Peer-Reviewed Original ResearchCitationsAltmetricThe evolving role of liver sinusoidal endothelial cells in liver health and disease
McConnell M, Kostallari E, Ibrahim S, Iwakiri Y. The evolving role of liver sinusoidal endothelial cells in liver health and disease. Hepatology 2023, 78: 649-669. PMID: 36626620, PMCID: PMC10315420, DOI: 10.1097/hep.0000000000000207.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsCitationsAltmetricMeSH Keywords and ConceptsConceptsLiver diseaseAlcohol-associated liver diseaseEndothelial cellsLiver transplant rejectionIschemia-reperfusion injuryLiver sinusoidal endothelial cellsSinusoidal endothelial cellsPortal hypertensionLiver inflammationMicrovascular thrombosisViral hepatitisReperfusion injuryTransplant rejectionLiver healthLiver pathologyLiver homeostasisLiver regenerationQuiescent phenotypePathological processesUnique populationDiseaseLSECLiver biologyGene expression profilesInflammation
2021
Obituary for Roberto J. Groszmann—The Father of Portal Hypertension
Shah V, Iwakiri Y, Boyer J. Obituary for Roberto J. Groszmann—The Father of Portal Hypertension. Hepatology 2021, 74: 1724-1726. DOI: 10.1002/hep.31996.Peer-Reviewed Original Research
Academic Achievements and Community Involvement
activity Associate Editor
Journal ServiceHepatology CommunicationsDetails2022 - Presentactivity Editorial Board
Professional OrganizationsHepatology InternationalDetails11/01/2014 - PresentDescriptionEditorial board memberactivity Reviewer
Peer Review Groups and Grant Study SectionsDepartment of Defense (DOD)Details10/02/2018 - PresentDescriptionGrant reviewer - the Liver Cancer peer review panelactivity Member
Meeting Planning and ParticipationSociety for Clinical and Translational Science (SCTS)Details2010 - Presentactivity Grant Reviewer
Peer Review Groups and Grant Study SectionsResearch Grants Council (RGC) of Hong KongDetails2014 - Present
Links & Media
Media
Immune cell infiltration to the portal tract of the liver
Macrophages (green) and T-cells (red) are infiltrated to the portal tract area of the liver in response to the induction of portal hypertension in rats. These cells play roles for portal tract fibrosis in the liver.
News
Social Media
Related Links
Get In Touch
Contacts
Yale School of Medicine
Department of Medicine (Digestive Diseases), PO Box 208019
New Haven, CT 06520-8019
United States
Locations
The Anlyan Center
Academic Office
300 Cedar Street, Ste S223B
New Haven, CT 06519
Administrative Support