Xiaoyong Yang, PhD
Professor of Comparative Medicine and of Cellular and Molecular PhysiologyCards
Appointments
Contact Info
Comparative Medicine
310 Cedar Street, PO Box 208016
New Haven, CT 06520-8016
United States
About
Titles
Professor of Comparative Medicine and of Cellular and Molecular Physiology
Biography
Dr. Xiaoyong Yang is Professor of Comparative Medicine and of Cellular and Molecular Physiology at Yale University School of Medicine. He received his B.S. from Nankai University, M.S. from Peking University, and Ph.D. from University of Alabama at Birmingham. He completed his postdoctoral training with Dr. Ronald Evans at The Salk Institute. Dr. Yang works at the intersection of diabetes, obesity, and cancer. He has made pioneering contributions to deciphering biological information encoded in protein modifications. Dr. Yang has published highly cited articles in scientific journals such as Cell, Cell Metabolism, Nature, Nature Medicine, and has been featured in public media outlets such as TIME, Daily Mail, NPR, and Scientific American. He has served on scientific review panels for the NIH, NASA, American Diabetes Association, American Cancer Society, The Medical Research Council, The Wellcome Trust, and other agencies worldwide. Dr. Yang is the founder of the Cancer Metabolism Initiative (CAMI) and a member of the Dean’s Faculty Advisory Council at Yale School of Medicine. He holds an adjunct professor position at Johns Hopkins University School of Medicine. Dr. Yang has played leadership roles in professional organizations as president of CADA and vice president of SAPA. He has been elected to the Connecticut Academy of Science and Engineering.
Appointments
Comparative Medicine
ProfessorPrimaryCellular & Molecular Physiology
ProfessorSecondary
Other Departments & Organizations
- Cancer Signaling Networks
- Cellular & Molecular Physiology
- Comparative Medicine
- Diabetes Research Center
- Graduate Program in Cellular and Molecular Physiology
- Liver Center
- Molecular Cell Biology, Genetics and Development
- Molecular Medicine, Pharmacology, and Physiology
- Yale Cancer Center
- Yale Center for Molecular and Systems Metabolism (YMSM)
- Yale Combined Program in the Biological and Biomedical Sciences (BBS)
- Yale Ventures
Education & Training
- Postdoctoral Fellow
- The Salk Institute (2008)
- PhD
- University of Alabama at Birmingham (2001)
- MS
- Peking University (1996)
- BS
- Nankai University (1993)
Research
Overview
The long-range goal of our research is to understand signaling and transcriptional mechanisms governing metabolism in response to environmental and genetic cues, and to design strategies to battle metabolic diseases.
Diet and the day/night cycle are principle environmental cues that control intermediary metabolism. Nutrient flux into the cell triggers protein modification by the amino sugar called N-acetylglucosamine (O-GlcNAc). This dynamic and reversible posttranslational modification is emerging as a key regulator of diverse cellular processes. Our first goal is to elucidate how O-GlcNAc acts as a nutrient sensor to couple systemic metabolic status to cellular regulation of signal transduction, transcription, and protein degradation. It is crucial to understand how perturbations in this posttranslational modification contribute to human diseases including diabetes, obesity, cancer and aging.
Both diet and light affect the body’s circadian rhythms. Our second goal is to unravel molecular links between the circadian clock and metabolic physiology. On the basis of our finding of broad expression and tissue-specific oscillation of nuclear receptors, we would like to determine potential roles of nuclear receptors in integrating circadian signals from nutritional cues and the light-sensing central clock to entrain peripheral clocks, and in coupling peripheral clocks to divergent metabolic outputs. There are the emerging links between circadian rhythm disorders and diabetes, obesity, and cardiovascular disease. We plan to explore novel strategies for treating these interrelated diseases.
To approach these goals, a combination of cutting-edge tools are employed, including biochemistry, molecular and cellular biology, mouse genetics, genomics, proteomics, metabolomics, and physiology.
Positions are available in my lab for highly motivated graduate students and postdoctoral fellows who are interested in exploring the frontier of research on metabolic physiology.
Medical Research Interests
ORCID
0000-0002-5315-7285
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
Anton Bennett, PhD
Marie Robert, MD
Carlos Fernandez-Hernando, PhD
Tamas Horvath, DVM, PhD
Zhongwu Liu, MD
Bernardo Stutz Xavier, PhD
Signal Transduction
Proteomics
Circadian Rhythm
Neoplasms
Publications
2024
Spatiotemporal control of subcellular O-GlcNAc signaling using Opto-OGT
Ong Q, Lim L, Goh C, Liao Y, Chan S, Lim C, Kam V, Yap J, Tseng T, Desrouleaux R, Wang L, Ler S, Lim S, Kim S, Sobota R, Bennett A, Han W, Yang X. Spatiotemporal control of subcellular O-GlcNAc signaling using Opto-OGT. Nature Chemical Biology 2024, 1-9. PMID: 39543398, DOI: 10.1038/s41589-024-01770-7.Peer-Reviewed Original ResearchConceptsO-GlcNAc transferaseO-GlcNAcLocalized to specific subcellular sitesResponse to insulin stimulationPost-translational modification of intracellular proteinsModification of intracellular proteinsO-GlcNAc signalingPost-translational modificationsTargeting O-GlcNAc transferaseSpatiotemporal controlMulticellular organismsOGT activityOrganelle functionO-GlcNAcylationSubcellular sitesMTORC activitySignal transductionIntracellular proteinsNutrient-sensing signalsCell signalingInsulin stimulationPlasma membraneGene expressionRegulatory mechanismsAkt phosphorylationmiR-33 deletion in hepatocytes attenuates NAFLD-NASH-HCC progression
Fernández-Tussy P, Cardelo M, Zhang H, Sun J, Price N, Boutagy N, Goedeke L, Cadena-Sandoval M, Xirouchaki C, Brown W, Yang X, Pastor-Rojo O, Haeusler R, Bennett A, Tiganis T, Suárez Y, Fernández-Hernando C. miR-33 deletion in hepatocytes attenuates NAFLD-NASH-HCC progression. JCI Insight 2024, 9: e168476. PMID: 39190492, PMCID: PMC11466198, DOI: 10.1172/jci.insight.168476.Peer-Reviewed Original ResearchConceptsMiR-33Regulation of biological processesMitochondrial fatty acid oxidationRegulation of lipid metabolismNon-alcoholic fatty liver diseaseDevelopment of effective therapeuticsFatty acid oxidationLipid synthesisProgression of non-alcoholic fatty liver diseaseMitochondrial functionTarget genesBiological processesComplex diseasesNon-alcoholic steatohepatitisLipid accumulationDeletionDevelopment of non-alcoholic fatty liver diseasePathway activationLipid metabolismProgress to non-alcoholic steatohepatitisAcid oxidationHCC progressionEffective therapeuticsTherapeutic targetHepatocellular carcinoma
2023
MKP1 promotes nonalcoholic steatohepatitis by suppressing AMPK activity through LKB1 nuclear retention
Qiu B, Lawan A, Xirouchaki C, Yi J, Robert M, Zhang L, Brown W, Fernández-Hernando C, Yang X, Tiganis T, Bennett A. MKP1 promotes nonalcoholic steatohepatitis by suppressing AMPK activity through LKB1 nuclear retention. Nature Communications 2023, 14: 5405. PMID: 37669951, PMCID: PMC10480499, DOI: 10.1038/s41467-023-41145-5.Peer-Reviewed Original ResearchMeSH Keywords and Concepts
2022
Ventromedial hypothalamic OGT drives adipose tissue lipolysis and curbs obesity
Wang Q, Zhang B, Stutz B, Liu ZW, Horvath TL, Yang X. Ventromedial hypothalamic OGT drives adipose tissue lipolysis and curbs obesity. Science Advances 2022, 8: eabn8092. PMID: 36044565, PMCID: PMC9432828, DOI: 10.1126/sciadv.abn8092.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsVentromedial hypothalamusWhite adipose tissueVMH neuronsAdipose tissueBody weightLipid metabolismRapid weight gainCounterregulatory responsesSympathetic activitySympathetic innervationAdipocyte hypertrophyTissue lipolysisNeuronal excitabilityFood intakePhysical activityObesity phenotypesGenetic ablationWeight gainHomeostatic set pointEnergy expenditureNeuronsInnervationLipolysisSignificant changesCellular sensors
2020
OGT suppresses S6K1-mediated macrophage inflammation and metabolic disturbance
Yang Y, Li X, Luan HH, Zhang B, Zhang K, Nam JH, Li Z, Fu M, Munk A, Zhang D, Wang S, Liu Y, Albuquerque JP, Ong Q, Li R, Wang Q, Robert ME, Perry RJ, Chung D, Shulman GI, Yang X. OGT suppresses S6K1-mediated macrophage inflammation and metabolic disturbance. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 16616-16625. PMID: 32601203, PMCID: PMC7368321, DOI: 10.1073/pnas.1916121117.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsRibosomal protein S6 kinase beta-1Macrophage proinflammatory activationGlcNAc signalingProinflammatory activationUnexpected roleWhole-body metabolismNutrient fluxesLipid accumulationImmune cell activationGlcNAcHomeostatic mechanismsMetabolic disturbancesBeta 1Cell activationDiet-induced metabolic dysfunctionDiet-induced obese miceActivationWhole-body insulin resistanceMacrophage inflammationGlcNAcylationOGTPeripheral tissuesPhosphorylationEnhanced inflammationInsulin resistanceO-GlcNAc transferase inhibits visceral fat lipolysis and promotes diet-induced obesity
Yang Y, Fu M, Li MD, Zhang K, Zhang B, Wang S, Liu Y, Ni W, Ong Q, Mi J, Yang X. O-GlcNAc transferase inhibits visceral fat lipolysis and promotes diet-induced obesity. Nature Communications 2020, 11: 181. PMID: 31924761, PMCID: PMC6954210, DOI: 10.1038/s41467-019-13914-8.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsMeSH KeywordsAcetylglucosamineAnimalsCell Line, TumorDietFastingGene DeletionHEK293 CellsHeLa CellsHomeostasisHumansIntra-Abdominal FatLipolysisMaleMiceMice, Inbred C3HMice, Inbred C57BLMice, KnockoutN-AcetylglucosaminyltransferasesObesityPerilipin-1PhosphorylationProtein Processing, Post-TranslationalSignal TransductionConceptsDiet-induced obesityVisceral fatExcessive visceral fat accumulationPerilipin 1Visceral fat accumulationVisceral fat lossTreatment of obesityPrimary risk factorAdipose tissue homeostasisUnhealthy obesityRisk factorsEnhanced lipolysisInhibits lipolysisFat accumulationO-GlcNAcylationFat lossObesityFat lipolysisRelated diseasesLipolysisInducible deletionLipid dropletsHexosamine biosynthetic pathwayFatTissue homeostasis
2019
O-GlcNAc transferase suppresses necroptosis and liver fibrosis
Zhang B, Li MD, Yin R, Liu Y, Yang Y, Mitchell-Richards KA, Nam JH, Li R, Wang L, Iwakiri Y, Chung D, Robert ME, Ehrlich BE, Bennett AM, Yu J, Nathanson MH, Yang X. O-GlcNAc transferase suppresses necroptosis and liver fibrosis. JCI Insight 2019, 4: e127709. PMID: 31672932, PMCID: PMC6948774, DOI: 10.1172/jci.insight.127709.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsReceptor-interacting protein kinase 3Liver fibrosisLiver diseaseHepatocyte necroptosisEthanol-induced liver injuryAlcoholic liver cirrhosisChronic liver diseaseMultiple liver diseasesWeeks of ageProtein expression levelsPortal inflammationLiver cirrhosisLiver injuryBallooning degenerationElevated protein expression levelsSpontaneous genetic modelFibrosisKey suppressorKey mediatorMiceProtein kinase 3CirrhosisExpression levelsGlcNAc levelsMixed lineage kinaseO-GlcNAcase targets pyruvate kinase M2 to regulate tumor growth
Singh JP, Qian K, Lee JS, Zhou J, Han X, Zhang B, Ong Q, Ni W, Jiang M, Ruan HB, Li MD, Zhang K, Ding Z, Lee P, Singh K, Wu J, Herzog RI, Kaech S, Wendel HG, Yates JR, Han W, Sherwin RS, Nie Y, Yang X. O-GlcNAcase targets pyruvate kinase M2 to regulate tumor growth. Oncogene 2019, 39: 560-573. PMID: 31501520, PMCID: PMC7107572, DOI: 10.1038/s41388-019-0975-3.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsMeSH KeywordsAcetylationAcetylglucosamineAnimalsAntigens, NeoplasmCarrier ProteinsCell Line, TumorDatasets as TopicDisease ProgressionFemaleGene Expression ProfilingGlycolysisHEK293 CellsHistone AcetyltransferasesHumansHyaluronoglucosaminidaseMaleMembrane ProteinsMiceN-AcetylglucosaminyltransferasesNeoplasm GradingNeoplasm StagingNeoplasmsProtein Processing, Post-TranslationalThyroid HormonesTissue Array AnalysisUp-RegulationXenograft Model Antitumor AssaysConceptsPyruvate kinase M2O-GlcNAcaseAerobic glycolysisO-GlcNAcylationKinase M2Lysine acetyltransferase activityTumor growthMetabolic rheostatAcetyltransferase activityGlcNAc transferaseMolecular basisMetabolic shiftHuman cancersGlycolysisCancer cellsHigh glucose conditionsGlucose availabilityTumor progressionGlucose conditionsExquisite controlGrowthRheostatCausative roleTargetEnzyme
2018
Adipocyte OGT governs diet-induced hyperphagia and obesity
Li MD, Vera NB, Yang Y, Zhang B, Ni W, Ziso-Qejvanaj E, Ding S, Zhang K, Yin R, Wang S, Zhou X, Fang EX, Xu T, Erion DM, Yang X. Adipocyte OGT governs diet-induced hyperphagia and obesity. Nature Communications 2018, 9: 5103. PMID: 30504766, PMCID: PMC6269424, DOI: 10.1038/s41467-018-07461-x.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsSerine/threonine residuesN-acetylglucosamine transferaseNutrient cuesThreonine residuesTranscriptional activationO-GlcNAcylationLipid desaturationIntracellular proteinsOGTHigh-fat diet-induced hyperphagiaDevelopment of obesityBaseline food intakeSignaling contributesLipid signalsCB1 signalingBrain axisChronic dysregulationFood intakeMetabolic diseasesPalatable foodPharmacological manipulationHyperphagiaObesityFat sensorSignaling
2017
Calcium-dependent O-GlcNAc signaling drives liver autophagy in adaptation to starvation
Ruan HB, Ma Y, Torres S, Zhang B, Feriod C, Heck RM, Qian K, Fu M, Li X, Nathanson MH, Bennett AM, Nie Y, Ehrlich BE, Yang X. Calcium-dependent O-GlcNAc signaling drives liver autophagy in adaptation to starvation. Genes & Development 2017, 31: 1655-1665. PMID: 28903979, PMCID: PMC5647936, DOI: 10.1101/gad.305441.117.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsMeSH KeywordsAdaptation, BiologicalAnimalsAutophagyAutophagy-Related Protein 5Autophagy-Related Protein-1 HomologCalcium SignalingCalcium-Calmodulin-Dependent Protein Kinase Type 2Cells, CulturedGlucagonHEK293 CellsHeLa CellsHumansInositol 1,4,5-Trisphosphate ReceptorsLiverMice, Inbred C57BLN-AcetylglucosaminyltransferasesNutritional Physiological PhenomenaConceptsAMPK-dependent phosphorylationLiver autophagyN-acetylglucosamine transferaseCalmodulin-dependent kinase IICalcium/calmodulin-dependent kinase IIWhole-body homeostasisULK proteinsNutrient homeostasisKinase IICalcium signalingAutophagic fluxGenetic ablationMetabolic adaptationAutophagyStarvationOGTPhosphorylationHomeostasisMouse liverProduction of glucoseKetone bodiesAdaptationSignalingProteinTransferase
Academic Achievements & Community Involvement
activity The National Institutes of Health
Peer Review Groups and Grant Study SectionsMemberDetailsStanding Member of Pathophysiology of Obesity and Metabolic Disease (POMD) Study Section07/01/2021 - Presentactivity Frontiers in Endocrinology
Journal ServiceAssociate EditorDetails08/05/2015 - Presentactivity Frontiers in Aging
Journal ServiceAssociate EditorDetails08/25/2020 - Presentactivity Journal of Endocrinology
Journal ServiceEditorDetailsSenior Editor09/01/2022 - Presentactivity Journal of Molecular Endocrinology
Journal ServiceEditorDetailsSenior Editor09/01/2022 - Present
News & Links
News
- February 26, 2024
CASE Announces Newly Elected Members
- November 09, 2023
Dr. Lei Zhang honored with American Cancer Society Postdoctoral Fellowship
- September 01, 2022Source: YaleNews
Study Finds Enzyme in the Brain Is a ‘Metastat’ for Body Weight
- August 31, 2022Source: Yale News
Study finds enzyme in the brain is a ‘metastat’ for body weight
Get In Touch
Contacts
Comparative Medicine
310 Cedar Street, PO Box 208016
New Haven, CT 06520-8016
United States
Events
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