Dr Gyorgy Fejer
Lecturer in Environmental Pathogens
School of Biomedical Sciences (Faculty of Health: Medicine, Dentistry and Human Sciences)
PhD in medicine, Semmelweis Medical School, 1998
Residency in Microbiology, 1995
PGCAP in Teaching and Learning in Higher Education
Plymouth University, 2013
Molecular mechanisms of lung macrophage functions in health and disease
Macrophages are crucially involved in various diseases such as Infectious and environmental pathogen induced conditions, cancer and metabolic disorders and also in normal tissue homeostasis. These cells exhibit, depending on their anatomical location, distinct biological properties. Studies exploring macrophages are of high scientific and clinical interest, but are hampered by the limited life-span and restricted numbers of primary tissue macrophages that can be obtained for such experiments. We established a novel, continuously growing, non-transformed model of lung alveolar macrophages (AMs), cells that play key roles in important diseases such as lung infection, asthma and chronic obstructive pulmonary disease (COPD). This model can replace and reduce in vivo studies involving macrophages and can contribute to the saving of lives of a very high number of experimental animals. Importantly, using our new system the detailed molecular analysis of scarcely available alveolar macrophages is possible. This made possible the identification of several, previously unknown innate immune phenomena in AMs (Fejer et al; PNAS 2013). Our laboratory now analyses the underlying molecular details using methods of molecular immunology, cell biology and proteomics. These studies help to understand relevant mechanisms of AM biology and lung diseases and can contribute to the development of drugs that influence AM activity in various pathology states.
List of recent publications 1. Woo M., Wood C., Kwon D., Park K. P., Fejer G* and Delorme V*. Mycobacterium tuberculosis infection and innate responses in a new, primary model of lung alveolar macrophages Frontiers in Immunology, 2018 9:438. doi.org/10.3389/fimmu.2018.00438 *corresponding author 2. Stichling N, Suomalainen M., Flatt J. W., Schmid M, Pacesa M., Hemmi S., Jungraithmayr W, Maler M. D., Freudenberg M. A., Plückthun A., May T, Köster K., Fejer G. and Greber U. F. Lung Macrophage Scavenger Receptor SR-A6 (MARCO) is an Adenovirus-Type specific Virus Entry Receptor PLoS Pathogens, 2018 14(3):e1006914. doi: 10.1371/journal.ppat.1006914. 3. Wise E. L, Pullan S. T, Márquez S, Paz V, Mosquera J. D., Zapata S., Jackson S. K., Fejer G, Trueba G., and Logue C. H. Isolation of Oropouche virus from a febrile patient in Ecuador; identified using metagenomic sequencing Emerging Infectious Diseases, 2018 24(5):935-937. doi.org/10.3201/eid2405.171569 4. Maler M, Nielsen P, Stichling N, Cohen I, Ruzsics Zs, Wood C, Engelhard P, Suomalainen M, Huber M, Müller-Quernheim J, Schamel W, Gordon S, Jahnen-Dechent W, Martin S. F., Jakob T, Greber U, Freudenberg M. A. and Fejer G. Key role of the scavenger receptor MARCO in mediating adenovirus infection and subsequent innate responses of macrophages Mbio 2017 8(4). pii: e00670-17. doi: 10.1128/mBio.00670-17. 5. Boorsma C, Putri K, Almeida A, Draijer C, Mauad T, Fejer G, Brandsma C, van den Berge M, Bossé Y, Sin D, Hao K, Olinga P, Timens W, Casini A, and Barbro Melgert A Potent Tartrate Resistant Acid Phosphatase Inhibitor to Study the Function of TRAP in Alveolar Macrophages Scientific Reports 2017 7(1):12570. doi: 10.1038/s41598-017-12623-w. 6. Rawson F, Hicks J, Dodd N, Abate W, Garrett D, Yip N, Fejer G, Downard A, Baronian K, Jackson S and Mendes P Fast, ultrasensitive detection of reactive oxygen species using an electrocatalytic intracellular nanosensor ACS Applied Materials & Interfaces 2015 7(42):23527-37 7. Fejer G*, Sharma S and Györy I Self-renewing macrophages - a new line of studies in mononuclear phagocytes Immunobiology 2015 220(2):169-174, invited review *corresponding author 8. Fejer G*, Wegener M, Györy I, Cohen I, Engelhard P, Voronov E, Manke T, Ruzsics Zs, Dölken L, Prazeres da Costa O, Branzk N, Huber M, Prasse A, Apte R, Galanos C and Freudenberg MA* Nontransformed, GM-CSF-dependent macrophage lines are a unique model to study tissue macrophage functions Proc Natl Acad Sci U S A 2013 110(24):E2191-8. *corresponding author 9. Fejer G., Freudenberg M., Greber U. F. and Gyory I Adenovirus triggered innate signalling pathways European Journal of Microbiology and Immunology 2011 1 (4) 279–288 10. Keck S, Müller I, Fejer G, Savic I, Nielsen P, Galanos C, Huber M and Freudenberg MA Absence of TRIF signaling in LPS-stimulated murine bone marrow-derived mast cells Journal of Immunology, 2011 186(9):5478-88 11. Lauterbach H, Bathke B, Gilles S, Traidl-Hoffmann C, Luber CA, Fejer G, Freudenberg MA, Davey GM, Vremec D, Kallies A, Wu L, Shortman K, Chaplin P, Suter M, O‘Keeffe M and Hochrein H The CD8a+ subset of DCs in mouse and human BDCA3+ DCs are major producers of IFN-λ in response to poly IC Journal of Experimental Medicine, 2010 207(12):2703-17 12. Schmidt M, Raghavan B, Müller V, Vogl T, Fejer G, Tchapchet S, Keck S, Kalis C, Nielsen P, Galanos C, Roth J, Skerra A, Martin SF, Freudenberg MA and Goebeler M Crucial role for human Toll-like receptor 4 in the development of contact allergy to nickel Nature Immunology, 2010 11(9):814-9 13. Siegemund S, Hartl A, Buttlar H, Dautel F, Raue R, Freudenberg M, Fejer G, Herden F, Buttner M, Koehler G, Kirschning C, Sparwasser T and G Alber Conventional bone marrow-derived dendritic cells contribute to Toll-like receptor-independent IFN-α/β production in response to inactivated parapoxvirus ovis Journal of Virology, 2009 83(18):9411-9422 14. Fejer*, G., L. Drechsel, J. Liese , U. Schleicher, Zs. Ruzsics, J. Imelli, U. Greber, S. Keck, B. Hildenbrand, A. Krug , C. Bogdan and M. A. Freudenberg* Key role of splenic myeloid DCs in the IFN- response to adenoviruses in vivo. PLoS Pathogens, 2008 4(11):e1000208. *corresponding author 15. Fejer*, G., A. Koroknai, F. Banati, I. Gyory, D. Salamon, H. Wolf, H. H. Niller and J. Minarovits. Latency type-specific distribution of epigenetic marks at the alternative promoters Cp and Qp of Epstein - Barr virus. Journal of General Virology 2008 89:1364-1370. *corresponding author 16. Martin S, Dudda J, Bachtanian E, Lembo A, Liller S, Dürr C, Heimesaat MM, Bereswill, Fejer G, Vassileva R, JakobT, Freudenberg N, Termeer CC, Johner C, Galanos C and M. A. Freudenberg 2008 Toll-like receptor and IL-12 signaling control susceptibility to contact hypersensitivity Journal of Experimental Medicine 2008 205(9):2151-62 17. Freudenberg, M. A., S. Tchaptchet, S. Keck, G. Fejer, M. Huber, N. Schutze, B. Beutler and C. Galanos. Lipopolysaccharide sensing an important factor in the innate immune response to Gram-negative bacteria infections: Benefits and hazards of LPS hypersensitivity. Immunobiology 2008 213:193-203. 18. Gerle#, B., A. Koroknai#, G. Fejer#, A. Bakos, F. Banati, K. Szenthe, H. Wolf, H. H. Niller, J. Minarovits and D. Salamon. 2007. Acetylated histone H3 and H4 mark the upregulated LMP2A promoter of Epstein-Barr virus in lymphoid cells. Journal of Virology 2007 81:13242-13247. # Shared first author 19. Fejer, G., K. Szalay, I. Gyory, M. Fejes, E. Kusz, S. Nedieanu, T. Pali, T. Schmidt, B. Siklodi, G. Lazar and E. Duda. Adenovirus infection dramatically augments lipopolysaccharide-induced TNF production and sensitizes to lethal shock. Journal of Immunology 2005 175:1498-1506. 20. Kalis, C., M. Gumenscheimer, N. Freudenberg, S. Tchaptchet, G. Fejer, A. Heit, S. Akira, C. Galanos and M. Freudenberg Requirement for TLR9 in the immunomodulatory activity of Propionibacterium acnes. Journal of Immunology 2005 174:4295-4300. 21. Gyory, I., J. Wu§, G. Fejer§, E. Seto, and K. L. Wright. PRDI-BF1 recruits the histone H3 methyltransferase G9a in transcriptional silencing. Nature Immunology 2004. 5:299-308. § Equal contribution 22. Osborne, A. R., H. Q. Zhang, G. Fejer, K. M. Palubin, M. I. Niesen, and G. Blanck. Oct-1 maintains an intermediate, stable state of HLA-DRA promoter repression in Rb-defective cells - An Oct-1-containing repressosome that prevents NF-Y binding to the HLA-DRA promoter. Journal of Biological Chemistry 2004.279:28911-28919. 23. Fejer, G., M. M. Medveczky, E. Horvath, B. Lane, Y. Chang, and P. G. Medveczky. The latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus interacts preferentially with the terminal repeats of the genome in vivo and this complex is sufficient for episomal DNA replication. Journal of General Virology 2003. 84:1451-1462.