RG Hegazy "Inflammatory Mechanisms"

The research group aims to uncover new pathways involved in induction and regulation of tissue‑resident T cells, bacterial interaction and intestinal inflammation that may offer new therapeutic targets in inflammatory diseases such as IBD.

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Research focus

The mammalian gastrointestinal tract is the largest organ of the human body beside the skin. It is the organ containing the largest number of immune cells and harbours a large and diverse population of commensal bacteria that exist in a symbiotic relationship with the host. In recent years, it has become increasingly clear that the composition of this gastrointestinal microbiome and its interaction with the host immune system strongly influences the health of the host.

One disease complex, in which maladaptation in this host microbial dialogue is involved, is inflammatory bowel disease (IBD). Here, this maladaptation leads to an aberrant immune response in the gut, resulting in recruitment of various lymphoid and myeloid effector cell populations and inflammation of gut tissue. The exact aetiology of IBD remains uncertain, but it is a multifactorial disease that involves a complex interplay between genetic, environmental, microbial, and immune factors.

Deciphering the complex interplay between both the genetic and environmental factors and the microbiota, is therefore of great biomedical importance. By combining mouse and human T cell immunology, mucosal immunology and animal models of disease as well as clinical specimens, we aim to identify environmental, microbial, and inflammatory drivers that promote maladaptation and gut tissue inflammation. We use a combination of cutting‑edge technologies, high throughput culture methods, cell and organoid cultures, physiological mouse models of colitis and analysis of well‑defined patient cohorts.

We specifically aim to uncover new pathways involved in induction and regulation of tissue‑resident T cells, bacterial interaction and intestinal inflammation that may offer new therapeutic targets in inflammatory diseases such as IBD.

Selected publications

  1. Hegazy* A.N., West* N.R., Stubbington, M.J.T., Wendt E.,  Suijker, K., Datsi, A., This, S., Danne, C., Campion, S., Duncan, S.H., Owens, B.M.J., Uhlig, H.H., McMichael, A., Oxford IBD Cohort Investigators, 
Bergthaler, A., Teichmann, S.A., Keshav, S., Powrie, F., 2017. Gut Microbiota Induce Local And Systemic CD4 T Cell Responses In Healthy Individuals That Are Altered In Inflammatory Bowel Diseases. Gastroenterology 153(5):1320-1337 (*equal contribution)
  2. Hegazy* A.N., West* N.R., Owens B.M.J., Görtz D., This S., Ryzhakov G., Bullers S., Rahman N., Owens R., Müller-Newen G., Powrie F., 2017. Oncostatin M drives intestinal inflammation in mice and its abundance 
predicts response to tumor necrosis factor-neutralizing therapy in 
 patients with inflammatory bowel disease. Nat Med 23(5):579-589 (*equal contribution)
  3. Hegazy*, A.N., Bhattacharya*, A., Deigendesch, N., Kosack, L., Cupovic, J., Kandasamy, R.K., Hildebrandt, A., Merkler, D., Kühl, A.A., Vilagos, B., Schliehe, C., Panse, I., Khamina, K., Baazim, H., Arnold, I., Flatz, L., Xu, H.C., Lang, P.A., Aderem, A., Takaoka, A., Superti-Furga, G., Colinge, J., Ludewig, B., Löhning, M., Bergthaler, A., 2015. Superoxide Dismutase 1 Protects Hepatocytes from Type I Interferon-Driven Oxidative Damage. Immunity 43, 974–986. (*equal contribution)
  4. Hegazy, A.N., Powrie, F., 2015. Microbiota RORgulates intestinal suppressor T cells. Science 349, 929–930.
  5. Flatz, L., Hegazy*, A.N., Bergthaler*, A., Verschoor*, A., Claus, C., Fernandez, M., Gattinoni, L., Johnson, S., Kreppel, F., Kochanek, S., Broek, M.V.D., Radbruch, A., Lévy, F., Lambert, P.-H., Siegrist, C.-A., Restifo, N.P., Löhning, M., Ochsenbein, A.F., Nabel, G.J., Pinschewer, D.D., 2010. Development of replication-defective lymphocytic choriomeningitis virus vectors for the induction of potent CD8+ T cell immunity. Nat Med 16, 339–345. (*equal contribution)
  6. Hegazy, A.N., Peine, M., Helmstetter, C., Panse, I., Fröhlich, A., Bergthaler, A., Flatz, L., Pinschewer, D.D., Radbruch, A., Löhning, M., 2010. Interferons Direct Th2 Cell Reprogramming to Generate a Stable GATA-3+T-bet+ Cell Subset with Combined Th2 and Th1 Cell Functions. Immunity 32, 116–128.
  7. Hegazy, A.N., Klein, C., 2008. Ex vivo priming of CD4 T cells converts immunological tolerance into effective antitumor immunity in a murine model of acute lymphoblastic leukemia. Leukemia 22, 2070–2079.
  8. Löhning, M., Hegazy, A.N., Pinschewer, D.D., Busse, D., Lang, K.S., Höfer, T., Radbruch, A., Zinkernagel, R.M., Hengartner, H., 2008. Long-lived virus-reactive memory T cells generated from purified cytokine-secreting T helper type 1 and type 2 effectors. J Exp Med 205, 53–61.

Collaborations

  1. Andreas Bergthaler, Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
  2. Lukas Flatz, Klinik für Dermatologie, Venerologie und Allergologie und Institut für Immunbiologie, Kantonsspital St. Gallen, Switzerland
  3. Sylvia Duncan, Microbial Ecology Group, Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, United Kingdom
  4. Sarah Teichmann and Mike Stubbington, Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom
  5. Nathaniel West, Genetech, San Francisco, United States
  6. Gerhard Mueller-Newen, Institute of Biochemistry and Molecular Biology, RWTH Aachen University, Aachen, Germany
  7. Thomas Schneider, Klinik für Gastroenterologie, Infektiologie und Rheumatologie, Charité - Universitätsmedizin Berlin (CBF)
  8. Max Löhning, Pitzer-Labor Arthroseforschung, Med. Klinik m.S. Rheumatologie u. Klin. Immunologie, Charité - Universitätsmedizin Berlin (CCM)
  9. Britta Siegmund, Klinik für Gastroenterologie, Infektiologie und Rheumatologie, Charité - Universitätsmedizin Berlin (CBF)
  10. Mir-Farzin Mashreghi, Koji Tokoyoda and Hyun-Dong Chang, Deutsches Rheumaforschungszentrum-Berlin