Chengyang Liu
Visiting Student 2019/20, Halene LabAbout
Research
Publications
2024
β-Cell Secretory Capacity Predicts Metabolic Outcomes over 6 Years following Human Islet Transplantation.
Flatt A, Matus A, Gallop R, Markmann E, Dalton-Bakes C, Peleckis A, Liu C, Naji A, Rickels M. β-Cell Secretory Capacity Predicts Metabolic Outcomes over 6 Years following Human Islet Transplantation. Diabetes 2024 PMID: 39630971, DOI: 10.2337/db24-0729.Peer-Reviewed Original ResearchPurified human pancreatic isletsB-cell massB-cell secretory capacityHuman pancreatic isletsSecretory capacityProinsulin secretory ratiosInsulin independenceBeta 2Pancreatic isletsMeasures of graft functionHormone metabolismSecretory ratioIntra-portal infusionOne-year post-transplantGlucose-potentiated arginineType 1 diabetesGraft functionPost-transplantB cellsIsletsMetabolic outcomesFasting glucagonHuman islet transplantationSustained insulin independenceBiliary atresia susceptibility gene EFEMP1 regulates extrahepatic bile duct elastic fiber formation and mechanics
Gupta K, Llewellyn J, Roberts E, Liu C, Naji A, Assoian R, Wells R. Biliary atresia susceptibility gene EFEMP1 regulates extrahepatic bile duct elastic fiber formation and mechanics. JHEP Reports 2024, 7: 101215. PMID: 39717503, PMCID: PMC11663959, DOI: 10.1016/j.jhepr.2024.101215.Peer-Reviewed Original ResearchExtrahepatic bile ductNeonatal extrahepatic bile ductsBiliary atresiaSusceptibility genesBile ductFibulin-3Genome wide association studiesExtracellular matrix protein 1Pressure myographyGene EFEMP1Elastic fibersExtracellular matrix proteinsAssociation studiesHuman extrahepatic bile ductsExtracellular matrix componentsElastic fiber organizationMatrix protein 1Decreased elastic fibersBile duct structuresMatrix proteinsFormation of elastic fibersFunctional relevanceGenesFiber formationNormal ductsHuman vascularized macrophage-islet organoids to model immune-mediated pancreatic β cell pyroptosis upon viral infection
Yang L, Han Y, Zhang T, Dong X, Ge J, Roy A, Zhu J, Lu T, Vandana J, de Silva N, Robertson C, Xiang J, Pan C, Sun Y, Que J, Evans T, Liu C, Wang W, Naji A, Parker S, Schwartz R, Chen S. Human vascularized macrophage-islet organoids to model immune-mediated pancreatic β cell pyroptosis upon viral infection. Cell Stem Cell 2024, 31: 1612-1629.e8. PMID: 39232561, PMCID: PMC11546835, DOI: 10.1016/j.stem.2024.08.007.Peer-Reviewed Original ResearchProinflammatory macrophagesActivation of proinflammatory macrophagesImmune cell changesCoxsackievirus B4Host damageAccumulation of proinflammatory macrophagesSingle-cell RNA sequencingMulti-omics platformsB cellsSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Marker expressionViral infectionViral exposureSyndrome coronavirus 2Endothelial cellsCell changesRNA sequencingSARS-CoV-2MacrophagesCell damageAutopsy samplesOrganoidsPyroptosis1736-P: Exploring Intrinsic Features of Human Pancreatic a- and ß-Cell Physiology Using Pseudoislets
ROZO A, ROMAN J, QIN W, LIU C, NAJI A, KAESTNER K, HOSHI T, STOFFERS D, DOLIBA N. 1736-P: Exploring Intrinsic Features of Human Pancreatic a- and ß-Cell Physiology Using Pseudoislets. Diabetes 2024, 73 DOI: 10.2337/db24-1736-p.Peer-Reviewed Original ResearchB cell physiologyIslet cell typesCell typesOxygen consumption rateA cellsCa2+ fluxBaseline oxygen consumption rateIntrinsic cellular functionsGlucose-mediated inhibitionCellular functionsNative isletsPancreatic AEffect of glucoseMitochondrial functionResponse to glucoseAmino acidsRate of secretionGenetic interventionsPseudoisletsB cell aggregatesGlucose-induced inhibitionHuman APhysiologyCell populationsIslets1507-P: Mixed-Meal Tolerance Test (MMTT) C-Peptide and BETA-2 Score Predict Underlying ß-Cell Secretory Capacity following Islet Transplantation for Type 1 Diabetes (T1D)
FLATT A, MATUS A, GALLOP R, MARKMANN E, DALTON-BAKES C, PELECKIS A, LIU C, NAJI A, RICKELS M. 1507-P: Mixed-Meal Tolerance Test (MMTT) C-Peptide and BETA-2 Score Predict Underlying ß-Cell Secretory Capacity following Islet Transplantation for Type 1 Diabetes (T1D). Diabetes 2024, 73 DOI: 10.2337/db24-1507-p.Peer-Reviewed Original ResearchMixed-meal tolerance testB-cell secretory capacityGlucose-potentiated arginineC-peptideBeta 2Secretory capacityBETA-2 scoreRepeated-measures correlation analysisYears post-transplantB cell functionIslet transplantationModerate effect sizeAllogeneic islet transplantationC-peptide/glucose ratioType 1 diabetesIslet graft functionGraft functionPost-transplantGraft monitoringTolerance testC-peptide/glucoseTransplantationLongitudinal cohortEffect sizeSS cellsNKX2-2 based nuclei sorting on frozen human archival pancreas enables the enrichment of islet endocrine populations for single-nucleus RNA sequencing
Xie G, Toledo M, Hu X, Yong H, Sanchez P, Liu C, Naji A, Irianto J, Wang Y. NKX2-2 based nuclei sorting on frozen human archival pancreas enables the enrichment of islet endocrine populations for single-nucleus RNA sequencing. BMC Genomics 2024, 25: 427. PMID: 38689254, PMCID: PMC11059690, DOI: 10.1186/s12864-024-10335-w.Peer-Reviewed Original ResearchConceptsSingle-nucleus RNA sequencingRNA sequencingNuclei sortingSnRNA-seqGene expressionEndocrine populationsFluorescence-activated nuclei sortingHuman isletsGene expression librariesNuclei isolation protocolSingle-cell RNA sequencingFrozen archival tissuesIsolated human isletsHuman pancreatic endocrine cellsSingle-cell transcriptomicsTranscriptomic studiesCytoplasmic contaminationTranscriptome profilingConclusionsOur workNKX2-2Isolated nucleiRNA integrityLiving cellsIsolation protocolPancreatic endocrine cellsModeling type 1 diabetes progression using machine learning and single-cell transcriptomic measurements in human islets
Patil A, Schug J, Liu C, Lahori D, Descamps H, Consortium T, Naji A, Kaestner K, Faryabi R, Vahedi G. Modeling type 1 diabetes progression using machine learning and single-cell transcriptomic measurements in human islets. Cell Reports Medicine 2024, 5: 101535. PMID: 38677282, PMCID: PMC11148720, DOI: 10.1016/j.xcrm.2024.101535.Peer-Reviewed Original ResearchSingle-cell transcriptomic measurementsGene expression of single cellsGene signatureSingle-cell analysisTranscriptional outputTranscriptomic measurementsUnique gene signatureNon-diabetic organ donorsAnalysis of isletsGene expressionAutoantibody-positive donorsPrediction of T1DHuman isletsBeta cellsCell typesT1D developmentSingle cellsGenesType 1 diabetes progressionCellsT1D onsetType 1 diabetesIsletsImmune cellsNon-diabetics
2023
Immunotherapy targeting B cells and long-lived plasma cells effectively eliminates pre-existing donor-specific allo-antibodies
Zhang Z, Markmann C, Yu M, Agarwal D, Rostami S, Wang W, Liu C, Zhao H, Ochoa T, Parvathaneni K, Xu X, Li E, Gonzalez V, Khadka R, Hoffmann J, Knox J, Scholler J, Marcellus B, Allman D, Fraietta J, Samelson-Jones B, Milone M, Monos D, Garfall A, Naji A, Bhoj V. Immunotherapy targeting B cells and long-lived plasma cells effectively eliminates pre-existing donor-specific allo-antibodies. Cell Reports Medicine 2023, 4: 101336. PMID: 38118406, PMCID: PMC10772570, DOI: 10.1016/j.xcrm.2023.101336.Peer-Reviewed Original ResearchConceptsChimeric antigen receptorLong-lived plasma cellsB-cell maturation antigenAllo-antibodiesMultiple myelomaB cellsChimeric antigen receptor-T therapyEfficacy of chimeric antigen receptorAllo-transplantationAnti-human leukocyte antigenTarget B cellsMemory B cellsCART-19T therapyMaturation antigenLeukocyte antigenAntigen receptorClinical efficacyMurine modelPlasma cellsClinical evaluationHyperacute rejectionDesensitization approachImmunotherapyTransplantationCheckpoint kinase 2 controls insulin secretion and glucose homeostasis
Chong A, Vandana J, Jeng G, Li G, Meng Z, Duan X, Zhang T, Qiu Y, Duran-Struuck R, Coker K, Wang W, Li Y, Min Z, Zuo X, de Silva N, Chen Z, Naji A, Hao M, Liu C, Chen S. Checkpoint kinase 2 controls insulin secretion and glucose homeostasis. Nature Chemical Biology 2023, 20: 566-576. PMID: 37945898, PMCID: PMC11062908, DOI: 10.1038/s41589-023-01466-4.Peer-Reviewed Original ResearchGlucose-stimulated insulin secretionInsulin secretionHuman β-cellsCynomolgus macaquesΒ-cellsImproved glucose clearanceType 2 diabetic human isletsDiabetic mouse modelDiabetic human isletsHuman β-cell lineDiscovery of insulinT2D conditionsΒ-cell lineGlucose toleranceGlucose clearanceMouse modelGlucose homeostasisMice showHuman isletsSecretionVivo studiesUntargeted metabolic profilingCell linesCheckpoint kinase 2Islets
2022
Alloantigen-specific Chimeric Antigen Receptor Regulatory T cell therapy in non-human primate islet transplantation
Ellis G, Coker K, Winn D, Deng M, Shukla D, Bhoj V, Milone M, Wang W, Liu C, Naji A, Duran-Struuck R, Riley J. Alloantigen-specific Chimeric Antigen Receptor Regulatory T cell therapy in non-human primate islet transplantation. The Journal Of Immunology 2022, 208: 175.21-175.21. DOI: 10.4049/jimmunol.208.supp.175.21.Peer-Reviewed Original ResearchCAR-TregsLarge animal modelPeripheral bloodIslet transplantationT cellsAnimal modelsRegulatory T cell therapyArtificial antigen presenting cellsCAR-Treg therapyEffector T cellsT-cell therapyAntigen presenting cellsOptimization of therapyType 1 diabetesCAR T cellsExpanded TregsTreg therapyAdoptive transferGraft rejectionAdoptive therapyDiabetic recipientsImmunosuppressive agentsNegative recipientsTreatment of cancerBlood glucose