People

Daria Esterhazy, PhD

We 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.

The Rockefeller University
- Postdoctoral Fellowship
2018

Howard Hughes Medical Institute
- Postdoctoral Fellowship
2013

ETH Zurich
Switzerland
- Postdoctoral Fellowship
2012

ETH Zurich
Zurich, Switzerland
PhD - metabolism, pancreatic islet biology
2010

University of Cambridge
Cambridge, UK
MSci - Biochemistry
2006

University of Cambridge
Cambridge, UK
BA - Natural Sciences
2005

Compartmentalized gut lymph node drainage dictates adaptive immune responses.
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.
PMID: 30988509

Gut immune cells have a role in food metabolism.
Esterházy D, Mucida D. Gut immune cells have a role in food metabolism. Nature. 2019 02; 566(7742):49-50.
PMID: 30710125

SnapShot: Gut Immune Niches.
Mucida D, Esterhazy D. SnapShot: Gut Immune Niches. Cell. 2018 09 06; 174(6):1600-1600.e1.
PMID: 30193116

Corrigendum: Commensal bacteria make GPCR ligands that mimic human signalling molecules.
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. Corrigendum: Commensal bacteria make GPCR ligands that mimic human signalling molecules. Nature. 2018 04 04; 556(7699):135.
PMID: 29620727

Commensal bacteria make GPCR ligands that mimic human signalling molecules.
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.
PMID: 28854168

Classical dendritic cells are required for dietary antigen-mediated induction of peripheral T(reg) cells and tolerance.
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.
PMID: 27019226

Absence of MHC class II on cDCs results in microbial-dependent intestinal inflammation.
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.
PMID: 27001748

Detection of FGF15 in plasma by stable isotope standards and capture by anti-peptide antibodies and targeted mass spectrometry.
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.
PMID: 26039452

Retinoic acid is essential for Th1 cell lineage stability and prevents transition to a Th17 cell program.
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.
PMID: 25769610

Phenotype and function of nasal dendritic cells.
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.
PMID: 25669151

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Advanced Postdoctoral Fellowship
Swiss National Science Foundation
2014 - 2016

Helmsley Trust Postdoctoral Fellowship
The Rockefeller University
2013 - 2014

Early Mobility Postdoctoral fellowship
Swiss National Science Foundation
2012 - 2013

Young Scientist Research Prize
Swiss Diabetes Foundation
2012

ETH Medal for PhD Thesis
ETH Zurich
2012

Gonville and Caius College Scholarship
University of Cambridge
2002 - 2006

Cambridge European Trust Scholarship
University of Cambridge
2002 - 2006