DariaEsterhazy02d6H6QHEe3DiFpmc0Kg5mby9si87roQdX1vDaria Esterhazy41.7886000000000087.598699999999993681Esterhazy, DariaImmunological niches in the digestive systemintestinal lymphaticspancreasWe study how tissue specific immunity is shaped in the digestive system under homeostatic conditions and how it can be perturbed to cause pathologies.
Immunological niches in the digestive system
Our goal is to understand what drives niche specific, or local, immunological differences between not only functional segments along the gut, but also the liver-biliary system and the pancreas. We postulate that this immune compartmentalization underlies the nature and site specificity of disease susceptibility, such as pathogen tropisms, food allergies, autoimmune diseases, chronic inflammatory diseases and cancers. Insight into how the immune system is wired in each niche will permit more tailored and potentially effective therapeutic strategies.
Research area I: Driving forces and cellular substrates of tissue-specific lymph nodes in the digestive system
Lymph nodes (LNs) are key sites for the initiation of tissue specific adaptive immunity. Along the gastrointestinal tract they are immunologically distinct (Esterhazy et al., Nature 2019), with the more proximal LNs being more tolerance-promoting and the more distal LNs more pro-inflammatory- but we wonder how extensive this paradigm is, what developmental, cellular and molecular forces underlie it, and how hardwired a LN tone is or if it can be re-established after a perturbation. Projects in the lab to address these questions include studying the active role of the gut tissue lymphatics and the lymph they carry, LN macrophages, and LN stromal cells in shaping LN niches.
Research area II: Immune crosstalk between the gut, pancreas, and liver
While the gut, pancreas, and liver are distinct organs, they are directly connected through shared LNs, vascular supply and ductal systems, such as the biliary and pancreatic ducts. This is due to their common developmental origin, and serves both metabolic and immunological co-ordination in response to common exposures. However, all three routes also offer unique modes of immune-modulation of one organ through more or less direct interaction with another branch of the digestive system. The extent of such reciprocal control of tissue-specific innate and adaptive immunity is our subject of investigation, with a particular focus on the impact on the pancreas and the implications for the etiology and control of pancreatic diseases such as type 1 and type 2 diabetes, pancreatitis, and pancreatic ductal adenocarcinoma.
Techniques used
We use a wide range of techniques in mice, including lymph node dissection, microsurgery, lymphatic vessel cannulation, pancreatic islet isolation, multimodal imaging, single cell gene expression analysis, gnotobiotics, and genetic manipulation of mice to model diseases or track immune events. We use a spectrum of gastrointestinal pathogens, and study human material to relate our work to human disease.Assistant Professorplugins:TwitterTwitterprns:awardConferredByaward conferred byprns:coAuthorOfcoauthor ofprns:emailEncryptedemail addressprns:endDateend dateprns:fullNamefull nameprns:hasAuthorListauthor listprns:hasNetworkhas networkprns:hasPublicationVenuepublished inprns:informationResourceReferenceinformation resource referenceprns:isPrimaryPositionis primary positionprns:latitudelatitudeprns:longitudelongitudeprns:mainImagephotoprns:maxWeightmaximum weightprns:medlineTAjournal title abbreviationprns:meshDescriptorUIMeSH DescriptorUIprns:meshSemanticGroupNameMeSH semantic group nameprns:minWeightminimum weightprns:numberOfAuthorsnumber of authorsprns:numberOfConnectionsnumber of connectionsprns:numberOfPublicationsnumber of publicationsprns:personIdPerson IDprns:personInPrimaryPositionperson in primary positionprns:physicalNeighborOfphysical neighborprns:pluginSearchableDataProfilesRNS Plugin Searchable Dataprns:positionInDepartmentposition in departmentprns:predicateNodepredicate nodeprns:publicationDatepublication dateprns:similarTosimilar toprns:sortOrdersort orderprns:startDatestart dateprns:trainingAtOrganizationeducational organizationprns:trainingLocationtraining locationprns:uniquenessWeightuniqueness weightprns:yearyearAcademic ArticleArticleDocumentbibo:pmidPubMed IdentifierAddressvivo:addressCitycityvivo:addressPostalCodepostal codevivo:addressStatestate or provincevivo:authorInAuthorshipselected publicationsvivo:authorRankauthor rank in publicationAuthorshipvivo:awardOrHonorawards and honorsAward or Honor Receiptvivo:degreeEarneddegree earnedDepartmentvivo:educationalTrainingeducation and trainingEducational Trainingvivo:freetextKeywordkeywordsvivo:hasResearchArearesearch areasvivo:hrJobTitleHR job titleInformation Resourcevivo:linkAnchorTextlink anchor textvivo:linkedAuthorlinked authorvivo:linkedInformationResourcelinked information resourcevivo:mailingAddressmailing addressvivo:majorFieldmajor field of degreevivo:overviewoverviewvivo:personInPositionpositionsPositionvivo:positionInOrganizationposition in organizationvivo:preferredTitlepreferred titleURLLinkvivo:webpagewebpagerdf:predicatepredicaterdf:typetyperdfs:labellabelConceptAgentfoaf:firstNamefirst namefoaf:lastNamelast nameOrganizationPersonD003713Anatomy1054240.763382Dendritic CellsJosephineButzJosephine Butz41.7886000000000087.598699999999993599Butz, JosephineEmeritus/Emerita, ProfessorChicago60637IL1.028610.0067748149research areas0.2209460.05523654coauthor of20.97713.7045860similar to1118selected publicationsFatimaAldarweeshFatima Aldarweesh41.7886000000000087.598699999999993733Aldarweesh, FatimaAssistant ProfessorMedicine-GastroenterologyMedicine-Infectious DiseasesMedicine-RheumatologyNeurobiologyAuthorship 1104603Authorship 1113052Authorship 1164892Authorship 123321228854168Cohen LJ, Esterhazy D, Kim SH, Lemetre C, Aguilar RR, Gordon EA, Pickard AJ, Cross JR, Emiliano AB, Han SM, Chu J, Vila-Farres X, Kaplitt J, Rogoz A, Calle PY, Hunter C, Bitok JK, Brady SFNatureCommensal bacteria make GPCR ligands that mimic human signalling molecules. Nature. 2017 09 07; 549(7670):48-53.Nature2017-08-30T00:00:002017Commensal bacteria make GPCR ligands that mimic human signalling molecules.25769610Brown CC, Esterhazy D, Sarde A, London M, Pullabhatla V, Osma-Garcia I, Al-Bader R, Ortiz C, Elgueta R, Arno M, de Rinaldis E, Mucida D, Lord GM, Noelle RJImmunityRetinoic acid is essential for Th1 cell lineage stability and prevents transition to a Th17 cell program. Immunity. 2015 Mar 17; 42(3):499-511.Immunity2015-03-10T00:00:002015Retinoic acid is essential for Th1 cell lineage stability and prevents transition to a Th17 cell program.22790173Vats D, Wang H, Esterhazy D, Dikaiou K, Danzer C, Honer M, Stuker F, Matile H, Migliorini C, Fischer E, Ripoll J, Keist R, Krek W, Schibli R, Stoffel M, Rudin MDiabetologiaMultimodal imaging of pancreatic beta cells in vivo by targeting transmembrane protein 27 (TMEM27). Diabetologia. 2012 Sep; 55(9):2407-16.Diabetologia2012-07-13T00:00:002012Multimodal imaging of pancreatic beta cells in vivo by targeting transmembrane protein 27 (TMEM27).30193116Mucida D, Esterhazy DCellSnapShot: Gut Immune Niches. Cell. 2018 09 06; 174(6):1600-1600.e1.Cell2018-09-06T00:00:002018SnapShot: Gut Immune Niches.AndrewKoh1mlmA4F1GuTQkntjbwjr93A=Andrew Koh41.7886000000000087.598699999999993756Koh, AndrewAssistant ProfessorAuthorship 1269146Authorship 12691511Authorship 1269168Authorship 1269172Authorship 1269186Authorship 12691918Authorship 126920412/2010ETH ZurichZurich, SwitzerlandETH Zurich, metabolism, pancreatic islet biologyPhDmetabolism, pancreatic islet biology06/2006University of CambridgeCambridge, UKUniversity of Cambridge, BiochemistryMSciBiochemistry06/2005University of CambridgeCambridge, UKUniversity of Cambridge, Natural SciencesBANatural SciencesUniversity of Cambridge20062002Cambridge European Trust ScholarshipUniversity of Cambridge20062002Gonville and Caius College Scholarship ETH Zurich2012ETH Medal for PhD ThesisSwiss Diabetes Foundation2012Young Scientist Research PrizeSwiss National Science Foundation20132012Early Mobility Postdoctoral fellowshipThe Rockefeller University20142013Helmsley Trust Postdoctoral FellowshipSwiss National Science Foundation20162014Advanced Postdoctoral Fellowship26039452Katafuchi T, Esterházy D, Lemoff A, Ding X, Sondhi V, Kliewer SA, Mirzaei H, Mangelsdorf DJCell metabolismDetection of FGF15 in plasma by stable isotope standards and capture by anti-peptide antibodies and targeted mass spectrometry. Cell Metab. 2015 Jun 02; 21(6):898-904.Cell Metab2015-06-02T00:00:002015Detection of FGF15 in plasma by stable isotope standards and capture by anti-peptide antibodies and targeted mass spectrometry.23430253Stützer I, Selevsek N, Esterházy D, Schmidt A, Aebersold R, Stoffel MThe Journal of biological chemistrySystematic proteomic analysis identifies ß-site amyloid precursor protein cleaving enzyme 2 and 1 (BACE2 and BACE1) substrates in pancreatic ß-cells. J Biol Chem. 2013 Apr 12; 288(15):10536-47.J Biol Chem2013-02-19T00:00:002013Systematic proteomic analysis identifies ß-site amyloid precursor protein cleaving enzyme 2 and 1 (BACE2 and BACE1) substrates in pancreatic ß-cells.18307315Esterházy D, King MS, Yakovlev G, Hirst JBiochemistryProduction of reactive oxygen species by complex I (NADH:ubiquinone oxidoreductase) from Escherichia coli and comparison to the enzyme from mitochondria. Biochemistry. 2008 Mar 25; 47(12):3964-71.Biochemistry2008-02-29T00:00:002008Production of reactive oxygen species by complex I (NADH:ubiquinone oxidoreductase) from Escherichia coli and comparison to the enzyme from mitochondria.27019226Esterházy D, Loschko J, London M, Jove V, Oliveira TY, Mucida DNature immunologyClassical dendritic cells are required for dietary antigen-mediated induction of peripheral T(reg) cells and tolerance. Nat Immunol. 2016 May; 17(5):545-55.Nat Immunol2016-03-28T00:00:002016Classical dendritic cells are required for dietary antigen-mediated induction of peripheral T(reg) cells and tolerance.25443493Esterházy D, Mucida DTrends in immunologySerum amyloid A proteins take retinol for a ride. Trends Immunol. 2014 Nov; 35(11):505-6.Trends Immunol2014-10-18T00:00:002014Serum amyloid A proteins take retinol for a ride.21907142Esterházy D, Stützer I, Wang H, Rechsteiner MP, Beauchamp J, Döbeli H, Hilpert H, Matile H, Prummer M, Schmidt A, Lieske N, Boehm B, Marselli L, Bosco D, Kerr-Conte J, Aebersold R, Spinas GA, Moch H, Migliorini C, Stoffel MCell metabolismBace2 is a ß cell-enriched protease that regulates pancreatic ß cell function and mass. Cell Metab. 2011 Sep 07; 14(3):365-77.Cell Metab2011-09-07T00:00:002011Bace2 is a ß cell-enriched protease that regulates pancreatic ß cell function and mass.2012ETH ZurichSwitzerlandETH Zurich, Postdoctoral FellowshipPostdoctoral Fellowship2013Howard Hughes Medical InstituteHoward Hughes Medical Institute, Postdoctoral FellowshipPostdoctoral Fellowship2018The Rockefeller UniversityThe Rockefeller University, Postdoctoral FellowshipPostdoctoral FellowshipAuthorship 129005630988509Esterházy D, Canesso MCC, Mesin L, Muller PA, de Castro TBR, Lockhart A, ElJalby M, Faria AMC, Mucida DNatureCompartmentalized gut lymph node drainage dictates adaptive immune responses. Nature. 2019 05; 569(7754):126-130.Nature2019-04-15T00:00:002019Compartmentalized gut lymph node drainage dictates adaptive immune responses.Authorship 1299712Authorship 129972330710125Esterházy D, Mucida DNatureGut immune cells have a role in food metabolism. Nature. 2019 02; 566(7742):49-50.Nature2019-02-01T00:00:002019Gut immune cells have a role in food metabolism.22460761Stützer I, Esterházy D, Stoffel MDiabetologiaThe pancreatic beta cell surface proteome. Diabetologia. 2012 Jul; 55(7):1877-89.Diabetologia2012-03-31T00:00:002012The pancreatic beta cell surface proteome.EricPamerEric Pamer41.7886000000000087.598699999999993819Pamer, EricProfessor27001748Loschko J, Schreiber HA, Rieke GJ, Esterházy D, Meredith MM, Pedicord VA, Yao KH, Caballero S, Pamer EG, Mucida D, Nussenzweig MCThe Journal of experimental medicineAbsence of MHC class II on cDCs results in microbial-dependent intestinal inflammation. J Exp Med. 2016 Apr 04; 213(4):517-34.J Exp Med2016-03-21T00:00:002016Absence of MHC class II on cDCs results in microbial-dependent intestinal inflammation.Authorship 13298214Authorship 132983325669151Lee H, Ruane D, Law K, Ho Y, Garg A, Rahman A, Esterházy D, Cheong C, Goljo E, Sikora AG, Mucida D, Chen BK, Govindraj S, Breton G, Mehandru SMucosal immunologyPhenotype and function of nasal dendritic cells. Mucosal Immunol. 2015 Sep; 8(5):1083-98.Mucosal Immunol2015-02-11T00:00:002015Phenotype and function of nasal dendritic cells.22628310Esterházy D, Akpinar P, Stoffel MBiological chemistryTmem27 dimerization, deglycosylation, plasma membrane depletion, and the extracellular Phe-Phe motif are negative regulators of cleavage by Bace2. Biol Chem. 2012 May; 393(6):473-84.Biol Chem2012-05-01T00:00:002012Tmem27 dimerization, deglycosylation, plasma membrane depletion, and the extracellular Phe-Phe motif are negative regulators of cleavage by Bace2.RaghuMirmiraRaghu Mirmira41.7886000000000087.598699999999993890Mirmira, RaghuProfessorD016282Chemicals & Drugs23660.965992Aspartic Acid EndopeptidasesAuthorship 154998835633180Wang P, Chen L, McIntosh CM, Lane JI, Li R, Xie SZ, Sattar H, Esterhazy D, Chong AS, Alegre MLAmerican journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant SurgeonsOral alloantigen exposure promotes donor-specific tolerance in a mouse model of minor-mismatched skin transplantation. Am J Transplant. 2022 10; 22(10):2348-2359.Am J Transplant2022-06-16T00:00:002022Oral alloantigen exposure promotes donor-specific tolerance in a mouse model of minor-mismatched skin transplantation.DavidZemmourzWdkBq51C8zMknJtY0fp/Cv/+94=David Zemmour41.7886000000000087.598699999999994189Zemmour, DavidAssistant ProfessorD050417Anatomy723970.742363Insulin-Secreting CellsKimberlyColeKimberly Cole41.7886000000000087.598699999999994259Cole, KimberlyAssistant ProfessorD053829Chemicals & Drugs28930.945281Amyloid Precursor Protein SecretasesD00007594212160.984737Intraepithelial Lymphocyteshttps://pamerlab.uchicago.eduPamer Lab websitehttps://drewkohlab.org/Koh Labhttps://voices.uchicago.edu/esterhazylab/Esterhazy Labhttps://www.zemmourlab.uchicago.edu/Zemmour Labhttp://voices.uchicago.edu/drsisodialab/Sisodia Labhttp://dfi.uchicago.eduDuchossois Family InstituteZemmourDavidAuthorship 161991737095603Honer M, Polara A, Kuwabara H, Jacobsen H, Pähler A, Hartung T, Caruso A, Esterhazy D, Stoffel M, Dannals RF, Wong DF, Borroni E, Gobbi LCJournal of labelled compounds & radiopharmaceuticalsRO6807936 as a novel positron emission tomography (PET) radiotracer for in vitro and in vivo visualization and quantification of beta-site amyloid precursor protein cleaving enzyme (BACE1) in the rodent and baboon brain. J Labelled Comp Radiopharm. 2023 07; 66(9):222-236.J Labelled Comp Radiopharm2023-05-11T00:00:002023RO6807936 as a novel positron emission tomography (PET) radiotracer for in vitro and in vivo visualization and quantification of beta-site amyloid precursor protein cleaving enzyme (BACE1) in the rodent and baboon brain.PathologyUniversity of ChicagoEugene B.Chang0mBqA6AbHszMknJtY0fp/Cv/+94=Eugene B. Chang41.78927490000000-87.601250000000001255Chang, Eugene B.ProfessorGeorgeBakris0GBoa7McCszMknJtY0fp/Cv/+94=George Bakris41.78927490000000-87.601250000000001393Bakris, GeorgeProfessorMaria-LuisaAlegre2mNlDqYHHMzMknJtY0fp/Cv/+94=Maria-Luisa Alegre41.78927490000000-87.60125000000000481Alegre, Maria-LuisaProfessorSangram S.SisodiaxHF6ArIaHeX5hHlsaUXv9Gq0+s+oSangram S. Sisodia41.78927490000000-87.60125000000000510Sisodia, Sangram S.ProfessorAnita S.Chong1mFhBK8SOfnamXNnYUHhvWD+6g==Anita S. Chong41.78927490000000-87.60125000000000535Chong, Anita S.ProfessorHusainSattarHusain Sattar41.78927490000000-87.60125000000000567Sattar, HusainProfessortrue1ProfessorProfessortrue1ProfessorProfessortrue1ProfessorProfessortrue1ProfessorProfessortrue1ProfessorProfessortrue1ProfessorProfessortrue1Assistant ProfessorAssistant Professortrue1Assistant ProfessorAssistant Professortrue1Assistant ProfessorAssistant Professortrue1Assistant ProfessorAssistant Professortrue1Emeritus/Emerita, ProfessorEmeritus/Emerita, Professortrue1Assistant ProfessorAssistant Professortrue1ProfessorProfessortrue1ProfessorProfessorMedicine-EndocrinologySurgery-Transplant