Shi-Ying Cai, DSc
Senior Research Scientist (Digestive Diseases)Cards
About
Titles
Senior Research Scientist (Digestive Diseases)
Biography
I am a trained molecular biologist. I am associated with Dr. James Boyer and studied molecular mechanisms of bile formation and cholestatic liver injury. My current study is focusing on the mechanism of bile acid initiating inflammatory response in hepatocytes and therapeutic targets of cholestatic liver injury. In addition, I am also interested in using comparative genomic approach to understand the structure and function relationship of bile salt transporters characterized in humans and rodents.
Last Updated on March 18, 2025.
Appointments
Digestive Diseases
Senior Research ScientistPrimary
Other Departments & Organizations
- All Institutions
- Digestive Diseases
- Hamburg House Affiliates
- Internal Medicine
Education & Training
- MS
- University of New Haven (2001)
- DSc
- Beijing Inst of Basic Medical Sciences (1992)
- MS
- Beijing Inst of Basic Medical Sciences (1989)
- BS
- Dalian University of Science and Technology (1986)
Research
Publications
2025
Conjugated bile acid-driven CD14+CD16+ monocyte infiltration promotes cholestatic liver injury by enhancing hepatocyte necroptosis
Zhu Z, Xu Z, Cao X, Zhao N, Lei J, Li L, Li X, Li Y, Li M, Ren T, Liu L, Boyer J, Cai S, Pan Q, Zhang X, Chai J. Conjugated bile acid-driven CD14+CD16+ monocyte infiltration promotes cholestatic liver injury by enhancing hepatocyte necroptosis. JHEP Reports 2025, 7: 101517. PMID: 40980164, PMCID: PMC12448010, DOI: 10.1016/j.jhepr.2025.101517.Peer-Reviewed Original ResearchCD14+ CD16+ monocytesCD16+ monocytesPeripheral blood mononuclear cellsCholestatic liver injuryTumor necrosis factor-alphaNecrosis factor-alphaObstructive cholestasisMonocyte infiltrationLevels of TNFaLiver injuryHepatocyte necroptosisNon-parenchymal cellsMultiplex immunofluorescenceFactor-alphaPeripheral blood mononuclear cell populationsAbstractText Label="Background &Analysis of tumor necrosis factor-alphaLiver non-parenchymal cellsCholestatic liver diseaseBlood mononuclear cellsLiver injury severityHepatic levelsScRNA-seqAbstractText Label="ImpactIntermediate monocytes
2024
Deficiency of myeloid NPC1 exacerbates liver injury and fibrosis by impairing macrophage efferocytosis
Guan D, Huang P, Liu X, Li Q, Zhang X, Liu N, Wang Y, Wan Y, Chai J, Cai S, Chen R, Ye Z. Deficiency of myeloid NPC1 exacerbates liver injury and fibrosis by impairing macrophage efferocytosis. Journal Of Advanced Research 2024, 72: 213-227. PMID: 39547438, PMCID: PMC12147626, DOI: 10.1016/j.jare.2024.11.020.Peer-Reviewed Original ResearchConceptsMouse model of liver injuryModels of liver injuryLiver injuryMouse modelTissue-specific deletionMethionine- and choline-deficientMacrophage efferocytosisLiver diseaseNiemann-Pick C1Levels of serum HMGB1Elevated expressionIn vitro mechanistic assaysElevated liver transaminasesAcute liver failureIn vitro mechanistic studiesMacrophage proinflammatory activationFunctional roleLiver function enzymesLiver transaminasesSerum HMGB1Inflammatory cytokines/chemokinesLiver failureKnockout miceHepatic macrophagesLiver inflammationIntegrative multiomic analysis identifies distinct molecular subtypes of NAFLD in a Chinese population
Ding J, Liu H, Zhang X, Zhao N, Peng Y, Shi J, Chen J, Chi X, Li L, Zhang M, Liu W, Zhang L, Ouyang J, Yuan Q, Liao M, Tan Y, Li M, Xu Z, Tang W, Xie C, Li Y, Pan Q, Xu Y, Cai S, Byrne C, Targher G, Ouyang X, Zhang L, Jiang Z, Zheng M, Sun F, Chai J. Integrative multiomic analysis identifies distinct molecular subtypes of NAFLD in a Chinese population. Science Translational Medicine 2024, 16: eadh9940. PMID: 39504356, DOI: 10.1126/scitranslmed.adh9940.Peer-Reviewed Original ResearchConceptsNonalcoholic fatty liver diseaseWhole-genome sequencingHepatocellular carcinomaMolecular subtypesLiver cirrhosisChinese cohort of patientsInfiltration of M1Risk of liver cirrhosisSerum metabolic analysisClinical diagnosisSubtype of nonalcoholic fatty liver diseaseCohort of patientsDevelopment of liver cirrhosisHepatocellular carcinoma developmentIntegrative multiomic analysisHealth care burdenFatty liver diseaseExpression of CYP1A2Urine specimensTreatment strategiesChinese cohortImpaired outcomeM2 macrophagesIntegrative multiomicsLiver diseaseHepatic GDP-fucose transporter SLC35C1 attenuates cholestatic liver injury and inflammation by inducing CEACAM1 N153 fucosylation
Zhang L, Xie P, Li M, Zhang X, Fei S, Zhao N, Li L, Xie Q, Xu Z, Tang W, Zhu G, Zhu Z, Xu Z, Li J, Zhang C, Boyer J, Chen W, Cai S, Pan Q, Chai J. Hepatic GDP-fucose transporter SLC35C1 attenuates cholestatic liver injury and inflammation by inducing CEACAM1 N153 fucosylation. Hepatology 2024, 81: 774-790. PMID: 38985995, PMCID: PMC11825483, DOI: 10.1097/hep.0000000000001003.Peer-Reviewed Original ResearchMouse model of cholestasisModel of cholestasisCholestatic liver injuryLiver injuryMouse modelCXCL2 expressionSolute carrier familyTandem mass spectrometry analysisPrimary mouse hepatocytesLiver-specific ablationMass spectrometry analysisProtein glycosylationSLC35C1Attenuate cholestatic liver injurySTAT3 SignalingBile ductular proliferationBile duct ligationCarrier familyLevels of serumCholic acid feedingMolecular mechanismsIncreased liver necrosisMRNA transcriptsFucosylationCXCL2 mRNA expression
2023
Organic Anion Transporting Polypeptide (OATP) 1B3 is a Significant Transporter for Hepatic Uptake of Conjugated Bile Acids in Humans
Pan Q, Zhu G, Xu Z, Zhu J, Ouyang J, Tong Y, Zhao N, Zhang X, Cheng Y, Zhang L, Tan Y, Li J, Zhang C, Chen W, Cai S, Boyer J, Chai J. Organic Anion Transporting Polypeptide (OATP) 1B3 is a Significant Transporter for Hepatic Uptake of Conjugated Bile Acids in Humans. Cellular And Molecular Gastroenterology And Hepatology 2023, 16: 223-242. PMID: 37146714, PMCID: PMC10394288, DOI: 10.1016/j.jcmgh.2023.04.007.Peer-Reviewed Original ResearchConceptsBA uptake transportersBile duct ligationHepatic neutrophil infiltrationCholestatic liver injuryProinflammatory cytokine productionCholic acid dietAdaptive protective responseLiver-specific overexpressionWild-type miceConjugated bile acidsUptake transportersPrimary hepatocytesUDCA feedingNeutrophil infiltrationBDL miceLiver injuryCytokine productionBile flowDuct ligationOrganic anion transporting polypeptide (OATP) 1B3Conjugated BAsTransgenic miceHepatic uptakeBile acidsProtective responseGut Microbiota Deficiency Exacerbates Liver Injury in Bile Duct Ligated Mice via Inflammation and Lipid Metabolism
Zhou X, Zhang X, Zhao N, Zhang L, Qiu W, Song C, Chai J, Cai S, Chen W. Gut Microbiota Deficiency Exacerbates Liver Injury in Bile Duct Ligated Mice via Inflammation and Lipid Metabolism. International Journal Of Molecular Sciences 2023, 24: 3180. PMID: 36834588, PMCID: PMC9960910, DOI: 10.3390/ijms24043180.Peer-Reviewed Original ResearchConceptsBile duct ligationGut microbiotaCholestatic liver injuryLiver injuryElevated expression of inflammatory genesGut microbiota homeostasisGut microbiota richnessBile duct ligation groupBile duct ligation miceFecal microbiota compositionElevated expressionLevels of plasma ALTPlasma ALTGram-negative bacteriaElevation of plasma ALTExpression of inflammatory genesMicrobiota homeostasisExacerbated liver injuryHepatic detoxification enzymesMicrobiota richnessMicrobiota compositionTotal bile acidsLigated miceMicrobiotaLevels of LPSHepatic TNFRSF12A promotes bile acid-induced hepatocyte pyroptosis through NFκB/Caspase-1/GSDMD signaling in cholestasis
Liao M, Liao J, Qu J, Shi P, Cheng Y, Pan Q, Zhao N, Zhang X, Zhang L, Tan Y, Li Q, Zhu J, Li J, Zhang C, Cai S, Chai J. Hepatic TNFRSF12A promotes bile acid-induced hepatocyte pyroptosis through NFκB/Caspase-1/GSDMD signaling in cholestasis. Cell Death Discovery 2023, 9: 26. PMID: 36690641, PMCID: PMC9871041, DOI: 10.1038/s41420-023-01326-z.Peer-Reviewed Original ResearchPrimary biliary cholangitisBile duct ligationCholestatic liver injuryObstructive cholestasisGenetic ablationHepatocyte pyroptosisC-Jun bindingPrimary mouse hepatocytesLiver injuryTumor necrosis factor receptor superfamily member 12ATHP1 cell linePrimary biliary cholangitis patientsMorphological featuresBile acidsCell deathMultiple tissuesLevels of pyroptosis-related proteinsCell linesTNFRSF12ACholestatic miceMechanistic studiesMouse hepatocytesBiliary cholangitisPyroptosisOC patientsRunt-related transcription factor-1 ameliorates bile acid–induced hepatic inflammation in cholestasis through JAK/STAT3 signaling
Zhang L, Pan Q, Zhang L, Xia H, Liao J, Zhang X, Zhao N, Xie Q, Liao M, Tan Y, Li Q, Zhu J, Li L, Fan S, Li J, Zhang C, Cai S, Boyer J, Chai J. Runt-related transcription factor-1 ameliorates bile acid–induced hepatic inflammation in cholestasis through JAK/STAT3 signaling. Hepatology 2023, 77: 1866-1881. PMID: 36647589, PMCID: PMC10921919, DOI: 10.1097/hep.0000000000000041.Peer-Reviewed Original ResearchConceptsJAK/STAT3Bile duct ligationInflammatory responseLiver injuryCholestatic patientsTranscription factor 1Duct ligationBile acidsLiver inflammatory responseCholestatic liver injuryHepatic inflammatory responseElevated bile acidsCholic acid dietFactor 1Cholic acid feedingLiver-specific ablationNew therapeutic targetsLiver-specific deletionCholestatic miceHepatic inflammationLiver inflammationInflammatory chemokinesHepatic expressionMouse modelAcid diet
2021
A homozygous R148W mutation in Semaphorin 7A causes progressive familial intrahepatic cholestasis
Pan Q, Luo G, Qu J, Chen S, Zhang X, Zhao N, Ding J, Yang H, Li M, Li L, Cheng Y, Li X, Xie Q, Li Q, Zhou X, Zou H, Fan S, Zou L, Liu W, Deng G, Cai S, Boyer JL, Chai J. A homozygous R148W mutation in Semaphorin 7A causes progressive familial intrahepatic cholestasis. EMBO Molecular Medicine 2021, 13: emmm202114563. PMID: 34585848, PMCID: PMC8573601, DOI: 10.15252/emmm.202114563.Peer-Reviewed Original ResearchConceptsTotal bile acidsIntrahepatic cholestasisSerum ALTHomozygous miceLiver functionSemaphorin 7ALiver bile acid levelsProgressive familial intrahepatic cholestasisMultidrug resistance-associated protein 2Hepatocyte hydropic degenerationElevated levelsHomozygous mutationBile acid levelsBile salt export pumpNormal liver functionResistance-associated protein 2Familial intrahepatic cholestasisBA transportersLiver histologyFamilial cholestasisFurther mechanistic studiesVertebral fracturesUnknown etiologyHydropic degenerationUrsodeoxycholic acid
2020
The Role of Bile Acid‐Mediated Inflammation in Cholestatic Liver Injury
Cai S, Li M, Boyer J. The Role of Bile Acid‐Mediated Inflammation in Cholestatic Liver Injury. 2020, 728-736. DOI: 10.1002/9781119436812.ch56.Peer-Reviewed Original ResearchCholestatic liver injuryBile acidsLiver injuryProinflammatory mediatorsInflammatory responseCauses of cholestasisAlcoholic liver diseasePrimary biliary cholangitisConjugated bile acidsEffects of drugsHepatic infiltrationBile acid transporterLiver transplantationViral hepatitisBiliary cholangitisBiliary cirrhosisMetabolic syndromeDuct obstructionLiver diseaseImmune cellsNeutrophil activationPathophysiological levelsCholangitisInflammationInjury
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Mailing Address
Yale School of Medicine
Department of Medicine (Digestive Diseases), PO Box 208019
New Haven, CT 06520-8019
United States