Daria Esterhazy

Assistant Professor
Websites
Research Summary
Immunological niches in the digestive system We study how immune homeostasis is maintained in the digestive system, and how its failure can lead to diseases such as food allergies, inflammatory bowel diseases (IBD), autoimmune diseases and cancer. In particular the lab explores immunologically distinct niches within the digestive system, studies how they are created by dietary, commensal colonization and infection history in the course of a lifetime, and what the systemic impact of each niche may be. We are analyzing the impact on the innate and adaptive immune system at the physiological, cellular and molecular level. Gastrointestinal lymphatic system. One key aspect we are studying is the gastrointestinal lymphatic system and how compartmentalized lymphatic drainage along the gut helps create different immunological environment. For example, we have found previously that gut segment specific infection (helminths in the upper small intestine versus bacteria in the colon) leads to dysfunction of only selective lymph nodes. We are currently expanding our studies to other pathogens and members of the commensal microbiome, but also to different dietary regimes, as nutrients are taken up in a site-selective manner as well. Most notably, the lymphatics of the upper small intestine are responsible for the absorption of dietary lipids and other hydrophobic nutrients and molecules. Both lymph fluid composition but also lymphatic architecture are influenced by these environmental factors, and likely help create distinct milieus. This may help sustain homeostatic conditions, but also support the chronicity of pathological conditions such as the metabolic syndrome, cancers or IBD. Pancreas and other branches of the digestive system. The digestive system also includes the pancreas, mesentery, and by extension liver, gall bladder, and the draining lymph nodes, of which several happen to be shared by these organs. We are interested in how the immune system of all these branches is influenced by gut luminal contents, and how it may communicate. This may occur via deliberate or inappropriate leakage of migratory immune cells, macro- and micro-molecules traveling through the interstitial space, common lymphatics or blood vessels. Through our studies we hope to better understand how for example gastrointestinal infections may trigger pathologies such as type 1 diabetes. Techniques used in the laboratory. We used a wide range of techniques including microsurgery, lymphatic vessel cannulation, pancreatic islet isolation, live and light sheet imaging of the vascular and immune systems, single cell analysis, mass spectrometry, and genetic manipulation of mice. In sum, our studies help define how tissue environments are created and influence the local immune system. While we focus on the digestive system, the concept that the concerted action of site specific exogenous factors, inherent tissue properties and connectivity to other organs determines the immunological output is likely relevant for other parts of the body as well. A more differentiated understanding of what shapes an immunological niche may help us devise more refined and effective therapeutic strategies to target organ-specific diseases.
Keywords
Immunological niches in the digestive system, intestinal lymphatics, pancreas
Education
  • ETH Zurich, Zurich, Switzerland, PhD metabolism, pancreatic islet biology 12/2010
  • University of Cambridge, Cambridge, UK, MSci Biochemistry 06/2006
  • University of Cambridge, Cambridge, UK, BA Natural Sciences 06/2005
  • ETH Zurich, Switzerland, Postdoctoral Fellowship 2012
  • Howard Hughes Medical Institute, Postdoctoral Fellowship 2013
  • The Rockefeller University, Postdoctoral Fellowship 2018
Awards & Honors
  • 2002 - 2006 Cambridge European Trust Scholarship University of Cambridge
  • 2002 - 2006 Gonville and Caius College Scholarship University of Cambridge
  • 2012 - 2013 Early Mobility Postdoctoral fellowship Swiss National Science Foundation
  • 2012 - ETH Medal for PhD Thesis ETH Zurich
  • 2012 - Young Scientist Research Prize Swiss Diabetes Foundation
  • 2013 - 2014 Helmsley Trust Postdoctoral Fellowship The Rockefeller University
  • 2014 - 2016 Advanced Postdoctoral Fellowship Swiss National Science Foundation
Publications
  1. Esterházy D, Canesso MCC, Mesin L, Muller PA, de Castro TBR, Lockhart A, ElJalby M, Faria AMC, Mucida D. Compartmentalized gut lymph node drainage dictates adaptive immune responses. Nature. 2019 05; 569(7754):126-130. View in: PubMed

  2. Esterházy D, Mucida D. Gut immune cells have a role in food metabolism. Nature. 2019 02; 566(7742):49-50. View in: PubMed

  3. Mucida D, Esterhazy D. SnapShot: Gut Immune Niches. Cell. 2018 09 06; 174(6):1600-1600.e1. View in: PubMed

  4. Cohen 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 SF. Commensal bacteria make GPCR ligands that mimic human signalling molecules. Nature. 2017 09 07; 549(7670):48-53. View in: PubMed

  5. Esterházy D, Loschko J, London M, Jove V, Oliveira TY, Mucida D. Classical dendritic cells are required for dietary antigen-mediated induction of peripheral T(reg) cells and tolerance. Nat Immunol. 2016 May; 17(5):545-55. View in: PubMed

  6. Loschko J, Schreiber HA, Rieke GJ, Esterházy D, Meredith MM, Pedicord VA, Yao KH, Caballero S, Pamer EG, Mucida D, Nussenzweig MC. Absence of MHC class II on cDCs results in microbial-dependent intestinal inflammation. J Exp Med. 2016 Apr 04; 213(4):517-34. View in: PubMed

  7. Katafuchi T, Esterházy D, Lemoff A, Ding X, Sondhi V, Kliewer SA, Mirzaei H, Mangelsdorf DJ. Detection 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. View in: PubMed

  8. Brown 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 RJ. Retinoic acid is essential for Th1 cell lineage stability and prevents transition to a Th17 cell program. Immunity. 2015 Mar 17; 42(3):499-511. View in: PubMed

  9. Lee 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 S. Phenotype and function of nasal dendritic cells. Mucosal Immunol. 2015 Sep; 8(5):1083-98. View in: PubMed

  10. Esterházy D, Mucida D. Serum amyloid A proteins take retinol for a ride. Trends Immunol. 2014 Nov; 35(11):505-6. View in: PubMed

  11. Stützer I, Selevsek N, Esterházy D, Schmidt A, Aebersold R, Stoffel M. Systematic 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. View in: PubMed

  12. Vats 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 M. Multimodal imaging of pancreatic beta cells in vivo by targeting transmembrane protein 27 (TMEM27). Diabetologia. 2012 Sep; 55(9):2407-16. View in: PubMed

  13. Esterházy D, Akpinar P, Stoffel M. Tmem27 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. View in: PubMed

  14. Stützer I, Esterházy D, Stoffel M. The pancreatic beta cell surface proteome. Diabetologia. 2012 Jul; 55(7):1877-89. View in: PubMed

  15. Esterházy 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 M. Bace2 is a ß cell-enriched protease that regulates pancreatic ß cell function and mass. Cell Metab. 2011 Sep 07; 14(3):365-77. View in: PubMed

  16. Esterházy D, King MS, Yakovlev G, Hirst J. Production 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. View in: PubMed