2021
Mitochondrial complex II in intestinal epithelial cells regulates T cell-mediated immunopathology
Fujiwara H, Seike K, Brooks MD, Mathew AV, Kovalenko I, Pal A, Lee HJ, Peltier D, Kim S, Liu C, Oravecz-Wilson K, Li L, Sun Y, Byun J, Maeda Y, Wicha MS, Saunders TL, Rehemtulla A, Lyssiotis CA, Pennathur S, Reddy P. Mitochondrial complex II in intestinal epithelial cells regulates T cell-mediated immunopathology. Nature Immunology 2021, 22: 1440-1451. PMID: 34686860, PMCID: PMC9351914, DOI: 10.1038/s41590-021-01048-3.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCase-Control StudiesCell CommunicationCells, CulturedColitisColonCytotoxicity, ImmunologicDisease Models, AnimalElectron Transport Complex IIEpithelial CellsFemaleGraft vs Host DiseaseHumansImmunity, MucosalIntestinal MucosaMice, Inbred BALB CMice, Inbred C57BLMice, TransgenicMitochondriaOxidative PhosphorylationSuccinic AcidT-LymphocytesConceptsGenetic experimental approachesCell-intrinsic featuresMetabolic flux studiesIntestinal epithelial cellsOxidative phosphorylationDisease severityT cell-mediated immunopathologyT cell-mediated colitisIntestinal epithelial cell damageProtein analysisSuccinate dehydrogenaseCell-mediated immunopathologyInflammatory bowel diseaseEpithelial cell damageHuman clinical samplesSuccinate levelsEpithelial cellsCritical roleSDHAHost diseaseBowel diseaseComplementary chemicalIntestinal diseaseT cellsMetabolic alterations
2020
Regulatory T-cell Depletion Alters the Tumor Microenvironment and Accelerates Pancreatic Carcinogenesis
Zhang Y, Lazarus J, Steele NG, Yan W, Lee HJ, Nwosu ZC, Halbrook CJ, Menjivar RE, Kemp SB, Sirihorachai VR, Velez-Delgado A, Donahue K, Carpenter ES, Brown KL, Irizarry-Negron V, Nevison AC, Vinta A, Anderson MA, Crawford HC, Lyssiotis CA, Frankel TL, Bednar F, di Magliano M. Regulatory T-cell Depletion Alters the Tumor Microenvironment and Accelerates Pancreatic Carcinogenesis. Cancer Discovery 2020, 10: 422-439. PMID: 31911451, PMCID: PMC7224338, DOI: 10.1158/2159-8290.cd-19-0958.Peer-Reviewed Original ResearchConceptsPancreatic cancerTreg depletionPancreatic carcinogenesisRegulatory T cellsT cell responsesMyeloid cell recruitmentMouse pancreatic cancerNew therapeutic approachesSmooth muscle actinPromotion of carcinogenesisImmune suppressionImmunosuppressive microenvironmentReceptors CCR1T cellsTherapeutic approachesCell recruitmentMouse modelMyeloid cellsMuscle actinRelated commentaryTumor progressionTregsTumor microenvironmentCancerFibroblast subsets
2019
NAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndrome
Fang EF, Hou Y, Lautrup S, Jensen MB, Yang B, SenGupta T, Caponio D, Khezri R, Demarest TG, Aman Y, Figueroa D, Morevati M, Lee HJ, Kato H, Kassahun H, Lee JH, Filippelli D, Okur MN, Mangerich A, Croteau DL, Maezawa Y, Lyssiotis CA, Tao J, Yokote K, Rusten TE, Mattson MP, Jasper H, Nilsen H, Bohr VA. NAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndrome. Nature Communications 2019, 10: 5284. PMID: 31754102, PMCID: PMC6872719, DOI: 10.1038/s41467-019-13172-8.Peer-Reviewed Original ResearchMeSH KeywordsAging, PrematureAnimalsAutophagy-Related Protein-1 HomologCaenorhabditis elegansCation Transport ProteinsDisease Models, AnimalDrosophila melanogasterHumansIntracellular Signaling Peptides and ProteinsMitophagyMutationNADNicotinamide-Nucleotide AdenylyltransferaseWerner SyndromeWerner Syndrome HelicaseConceptsWerner syndromeWerner DNA helicasePremature aging diseaseDrosophila melanogaster modelStem cell dysfunctionCaenorhabditis elegansDNA helicaseOrganismal levelImpaired mitochondrial functionMitochondrial qualityWS phenotypeImpaired mitophagyMitophagyMitochondrial functionDCT-1Ubiquitous moleculeSevere metabolic phenotypeMetabolic phenotypePhenotypeW patientsMetabolic dysfunctionCell dysfunctionMetabolic deficitsTherapeutic interventionsUnderlying mechanism