Mihály Józsi

Mihály Józsi Ph.D.

Professor

Email: mihaly.jozsi(at)ttk.elte.hu

Publications (MTMT)
Scientometric data (MTMT)

Short CV.:

M.Sc.: 1997, biology and English translation, Eötvös Loránd University, Budapest
Ph.D.: 2002, immunology, Eötvös Loránd University, Budapest
Habilitation: 2016, biology, Eötvös Loránd University, Budapest
D.Sc.: 2018, biology, Hungarian Academy of Sciences
2002-2006, postdoctoral researcher at Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie – Hans-Knöll-Institut, Jena, Germany
2006-2012, junior research group leader, Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie – Hans-Knöll-Institut, Jena, Germany
2012-2017, senior research fellow, head of MTA-ELTE "Lendület" Complement Research Group at the Department of Immunology, Eötvös Loránd University
2017-2020, associate professor at the Department of Immunology, Eötvös Loránd University
scholarships, fellowships: DAAD-scholarship (2001, 5 months), Eötvös Fellowship of the Hungarian State (2002, 6 months), Humboldt Research Fellowship (Alexander-von-Humboldt Stiftung, 2003-2004, 21 months)
prizes: BioScience-prize (2003), Medac Forschungspreis (2004, 2007)
current position (2020-): professor, head of department, head of the Complement Research Group at the Department of Immunology, Eötvös Loránd University; director of Bolyai College (https://www.bolyai.elte.hu/)

Research interest:

My research concerns the complement system of innate immunity, particularly the function and regulation of the alternative complement pathway, the structure and function of factor H and factor H-related proteins. Complement is involved in the pathomechanism of several diseases. Dysregulation of the alternative pathway, polymorphisms and mutations in factor H or anti-factor H autoantibodies play a role in various diseases, including age-related macular degeneration (a leading cause of blindness in the Western world) and the kidney diseases atypical hemolytic uremic syndrome and dense deposit disease). Our main aim is to unveil the physiological roles of factor H and factor H-related proteins, in order to understand their role in diseases, which could then lead to tailored treatments in the future.

Keywords: innate immunity, complement system, autoimmunity, complement-mediated diseases, factor H protein family, pentraxins

Members of the "Factor H and complement regulation" research group

Bacsa Erika (PhD student)
Bencze Dániel (PhD student)
Espárné Dr. Schneider Andrea (research fellow)
Hammad Hani Hashim (PhD student)
Dr. Józsi Mihály Krisztián (professor, head of the research group)
Dr. Kövesdi Dorottya (senior research fellow)
Matola Alexandra (PhD student)
Dr. Szakács Dávid (research fellow)
Dr. Uzonyi Barbara (research fellow)

Research projects

1. Interaction of factor H with immune cells.

Factor H is a major regulator of the alternative complement pathway. Its binding to receptors and influence on cellular functions, however, are poorly characterized. We recently showed that factor H, when bound to the human-pathogenic yeast Candida albicans, enhances the adhesion and activation of neutrophil granulocytes (Losse et al. 2010). In this project, we investigate the interaction of factor H with neutrophils, macrophages and dendritic cells.

Related publications:

Józsi M, Schneider AE, Kárpáti É, Sándor N. (2019) Complement factor H family proteins in their non-canonical role as modulators of cellular functions. Semin Cell Dev Biol. 85:122-131. (Review)
Schneider AE, Sándor N, Kárpáti É, Józsi M. (2016) Complement factor H modulates the activation of human neutrophil granulocytes and the generation of neutrophil extracellular traps. Mol. Immunol. 72:37-48.
Svoboda E, Schneider AE, Sándor N, Lermann U, Staib P, Kremlitzka M, Bajtay Z, Barz D, Erdei A, Józsi M. (2015) Secreted aspartic protease 2 of Candida albicans inactivates factor H and the macrophage factor H-receptors CR3 (CD11b/CD18) and CR4 (CD11c/CR4). Immunol. Lett. 168:13-21.
Losse J, Zipfel PF, Józsi M. (2010) Factor H and factor H-related protein 1 bind to human neutrophils via complement receptor 3, mediate attachment to Candida albicans, and enhance neutrophil antimicrobial activity. J. Immunol. 184:912-921.

2. Function of factor H-related proteins.

In addition to the complement inhibitor factor H, the factor H protein family includes five factor H-related (CFHR) molecules. In contrast to factor H, the function of the CFHRs is less characterized and controversial. Our aim is to understand the physiological role of the CFHR proteins and their association with certain diseases. We investigate their role in complement activation and interaction with pentraxins, which are soluble pattern recognition molecules of the innate immune system. We particularly analyze the interaction of CFHRs with the acute phase protein C-reactive protein and pentraxin 3 (PTX3), which is produced locally during inflammation and infection. CRP and PTX3 activate complement but also bind complement inhibitory molecules, such as factor H.

Related publications:

Papp A, Papp K, Uzonyi B, Cserhalmi M, Csincsi ÁI, Szabó Z, Bánlaki Z, Ermert D, Prohászka Z, Erdei A, Ferreira VP, Blom AM, Józsi M. (2022) Complement Factor H-Related Proteins FHR1 and FHR5 Interact With Extracellular Matrix Ligands, Reduce Factor H Regulatory Activity and Enhance Complement Activation. Front. Immunol. 13:845953.
Kárpáti É, Papp A, Schneider AE, Hajnal D, Cserhalmi M, Csincsi ÁI, Uzonyi B, Józsi M. (2020) Interaction of the Factor H Family Proteins FHR-1 and FHR-5 With DNA and Dead Cells: Implications for the Regulation of Complement Activation and Opsonization. Front. Immunol. 11:1297.
Cserhalmi M, Csincsi ÁI, Mezei Z, Kopp A, Hebecker M, Uzonyi B, Józsi M. (2017) The Murine Factor H-Related Protein FHR-B Promotes Complement Activation. Front Immunol. 8:1145.
Csincsi ÁI, Szabó Z, Bánlaki Z, Uzonyi B, Cserhalmi M, Kárpáti É, Tortajada A, Caesar JJE, Prohászka Z, Jokiranta TS, Lea SM, Rodríguez de Córdoba S, Józsi M. (2017) FHR-1 Binds to C-Reactive Protein and Enhances Rather than Inhibits Complement Activation. J Immunol. 199:292-303.
Józsi M, Tortajada A, Uzonyi B, Goicoechea de Jorge E, Rodríguez de Córdoba S. (2015) Factor H-related proteins determine complement-activating surfaces. Trends Immunol. 36:374-384.
Csincsi ÁI, Kopp A, Zöldi M, Bánlaki Z, Uzonyi B, Hebecker M, Caesar JJ, Pickering MC, Daigo K, Hamakubo T, Lea SM, Goicoechea de Jorge E, Józsi M. (2015) Factor H-related protein 5 interacts with pentraxin 3 and the extracellular matrix and modulates complement activation. J Immunol. 194:4963-4973.
Hebecker and Józsi. (2012) Factor H-related Protein 4 Activates Complement by Serving as a Platform for the Assembly of Alternative Pathway C3 Convertase via Its Interaction with C3b Protein. J. Biol. Chem. 2012 Jun 1;287(23):19528-19536.
Kopp et al. (2012) Atypical hemolytic uremic syndrome-associated variants and autoantibodies impair binding of factor H and factor H-related protein 1 to pentraxin 3. J. Immunol. 189:1858-1867.
Braunschweig and Józsi. (2011) Human pentraxin 3 binds to the complement regulator C4b-binding protein. PLoS One. 6:e23991.
Hebecker et al. (2010) Molecular basis of C-reactive protein binding and modulation of complement activation by factor H-related protein 4. Mol. Immunol. 47:1347-1355.

3. Characterization of anti-factor H autoantibodies.

Dysregulation of the alternative complement pathway is implicated in the severe kidney diseases atypical hemolytic uremic syndrome and C3 glomerulopathies (including dense deposit disease). Some of the patients have circulating autoantibodies to factor H. Our aims are the detailed functional characterization and epitope mapping of the autoantibodies in order to understand their role in disease.

Related publications:

Uzonyi B, Szabó Z, Trojnár E, Hyvärinen S, Uray K, Nielsen HH, Erdei A, Jokiranta TS, Prohászka Z, Illes Z, Józsi M. (2021) Autoantibodies Against the Complement Regulator Factor H in the Serum of Patients With Neuromyelitis Optica Spectrum Disorder. Front. Immunol. 12:660382.
Nozal et al. (2016) Heterogeneity but individual constancy of epitopes, isotypes and avidity of factor H autoantibodies in atypical hemolytic uremic syndrome. Mol. Immunol. 70:47-55.
Bhattacharjee et al. (2015) The Major Autoantibody Epitope on Factor H in Atypical Hemolytic Uremic Syndrome Is Structurally Different from Its Homologous Site in Factor H-related Protein 1, Supporting a Novel Model for Induction of Autoimmunity in This Disease. J Biol Chem. 290:9500-9510.
Strobel et al. (2011) Factor H-related protein 1 neutralizes anti-factor H autoantibodies in autoimmune hemolytic uremic syndrome. Kidney Int. 80:397-404.
Strobel et al. (2010) Functional analyses indicate a pathogenic role of factor H autoantibodies in atypical haemolytic uraemic syndrome. Nephrol. Dial. Transplant. 25:136-144.
Józsi et al. (2008) Factor H autoantibodies in atypical hemolytic uremic syndrome correlate with CFHR1/CFHR3 deficiency. Blood. 111:1512-1514.
Józsi et al. (2007) Anti-factor H autoantibodies block C-terminal recognition function of factor H in hemolytic uremic syndrome. Blood. 110:1516-1518.

Methods:

recombinant protein expression
mutagenesis
ELISA
complement activation assays
SDS-PAGE and Western blot
flow cytometry
microscopy

Support:

SciFiMed, 899163, H2020 FET-OPEN (https://www.scifimed.eu/); Screening of inFlammation to enable personalized Medicine (2021-2024).
Nemzeti Gyógyszerkutatási és Fejlesztési Laboratórium (PharmaLab, résztéma-vezető), RRF-2.3.1-21-2022-00015 (2022-2026).
2020-1.1.6-JÖVŐ-2021-00010, Koronavírus fertőzéssel szemben természetes védettséget adó faktorok vizsgálata és alkalmazása plazmaterápiában (2021-2024).
Kidneeds Foundation (Iowa, US), (The role of complement convertases), (2020-2021, 2023/24).
LP2012-43, in frame of the „Lendület” Program of the Hungarian Academy of Sciences (2012-2017)
K 109055, Hungarian Scientific Research Fund (OTKA) (The role of the CFHR1 and CFHR3 human serum proteins related to factor H, in physiological and pathological processes) (2014-2018)
Kidneeds Foundation (Iowa, US) (Studying the function of the CFHR5 molecule) (2016-2018)
NKFI 125219, (Functional analysis of the human complement factor H molecular family) (2017-2021)
Institutional Excellence Program of the Ministry of Human Capacities of Hungary (2017-2019)

Selected publications:

Smith RJH, Appel GB, Blom AM, Cook HT, D'Agati VD, Fakhouri F, Fremeaux-Bacchi V, Józsi M, Kavanagh D, Lambris JD, Noris M, Pickering MC, Remuzzi G, de Córdoba SR, Sethi S, Van der Vlag J, Zipfel PF, Nester CM. (2019) C3 glomerulopathy - understanding a rare complement-driven renal disease. Nat Rev Nephrol. 15:129-143.
Cserhalmi M, Uzonyi B, Merle NS, Csuka D, Meusburger E, Lhotta K, Prohászka Z, Józsi M. (2017) Functional Characterization of the Disease-Associated N-Terminal Complement Factor H Mutation W198R. Front Immunol. 8:1800.
Józsi M. (2017) Factor H Family Proteins in Complement Evasion of Microorganisms. Front Immunol. 8:571.
Csincsi ÁI, Szabó Z, Bánlaki Z, Uzonyi B, Cserhalmi M, Kárpáti É, Tortajada A, Caesar JJE, Prohászka Z, Jokiranta TS, Lea SM, Rodríguez de Córdoba S, Józsi M. (2017) FHR-1 Binds to C-Reactive Protein and Enhances Rather than Inhibits Complement Activation. J Immunol. 199:292-303.
Mészáros T, Csincsi ÁI, Uzonyi B, Hebecker M, Fülöp TG, Erdei A, Szebeni J, Józsi M. (2016) Factor H inhibits complement activation induced by liposomal and micellar drugs and the therapeutic antibody rituximab in vitro. Nanomedicine. 12:1023–1031.
Józsi M, Tortajada A, Uzonyi B, Goicoechea de Jorge E, Rodríguez de Córdoba S. (2015) Factor H-related proteins determine complement-activating surfaces. Trends Immunol. 36:374-384.
Csincsi ÁI, Kopp A, Zöldi M, Bánlaki Z, Uzonyi B, Hebecker M, Caesar JJ, Pickering MC, Daigo K, Hamakubo T, Lea SM, Goicoechea de Jorge E, Józsi M. (2015) Factor H-related protein 5 interacts with pentraxin 3 and the extracellular matrix and modulates complement activation. J Immunol. 194:4963-4973.
Bhattacharjee A, Reuter S, Trojnár E, Kolodziejczyk R, Seeberger H, Hyvärinen S, Uzonyi B, Szilágyi Á, Prohászka Z, Goldman A, Józsi M, Jokiranta TS. (2015) The Major Autoantibody Epitope on Factor H in Atypical Hemolytic Uremic Syndrome Is Structurally Different from Its Homologous Site in Factor H-related Protein 1, Supporting a Novel Model for Induction of Autoimmunity in This Disease. J Biol Chem. 290:9500-9510.
Hebecker M, Alba-Domínguez M, Roumenina LT, Reuter S, Hyvärinen S, Dragon-Durey MA, Jokiranta TS, Sánchez-Corral P, Józsi M. An Engineered Construct Combining Complement Regulatory and Surface-Recognition Domains Represents a Minimal-Size Functional Factor H. J Immunol. 2013 Jul 15;191(2):912-21.
Svobodová E, Staib P, Losse J, Hennicke F, Barz D, Józsi M. Differential Interaction of the Two Related Fungal Species Candida albicans and Candida dubliniensis with Human Neutrophils. J Immunol. 2012 Sep 1;189(5):2502-11
Kopp A, Strobel S, Tortajada A, Rodríguez de Córdoba S, Sánchez-Corral P, Prohászka Z, López-Trascasa M, Józsi M. Atypical Hemolytic Uremic Syndrome-Associated Variants and Autoantibodies Impair Binding of Factor H and Factor H-Related Protein 1 to Pentraxin 3. J Immunol. 2012 Aug 15;189(4):1858-67.
Hebecker M, Józsi M. Factor H-related Protein 4 Activates Complement by Serving as a Platform for the Assembly of Alternative Pathway C3 Convertase via Its Interaction with C3b Protein. J Biol Chem. 2012 Jun 1;287(23):19528-36.
Strobel S, Abarrategui-Garrido C, Fariza-Requejo E, Seeberger H, Sánchez-Corral P, Józsi M. Factor H-related protein 1 neutralizes anti-factor H autoantibodies in autoimmune hemolytic uremic syndrome. Kidney Int. 2011 Aug;80(4):397-404.
Braunschweig A, Józsi M. Human Pentraxin 3 Binds to the Complement Regulator C4b-Binding Protein. PLoS One. 2011;6(8):e23991.
Strobel S, Zimmering M, Papp K, Prechl J, Józsi M. Anti-factor B autoantibody in dense deposit disease. Mol Immunol. 2010 Apr;47(7-8):1476-83.
Hebecker M, Okemefuna AI, Perkins SJ, Mihlan M, Huber-Lang M, Józsi M. Molecular basis of C-reactive protein binding and modulation of complement activation by factor H-related protein 4. Mol Immunol. 2010 Mar;47(6):1347-1355.
Losse J, Zipfel PF, Józsi M. Factor H and Factor H-Related Protein 1 Bind to Human Neutrophils via Complement Receptor 3, Mediate Attachment to Candida albicans, and Enhance Neutrophil Antimicrobial Activity. J Immunol. 2010 Jan 15;184(2):912-21.
Mihlan M, Stippa S, Józsi M, Zipfel PF. Monomeric CRP contributes to complement control in fluid phase and on cellular surfaces and increases phagocytosis by recruiting factor H. Cell Death Differ. 2009 Dec;16(12):1630-40
Józsi M, Zipfel PF. Factor H family proteins and human diseases. Trends Immunol. 2008 Aug;29(8):380-7.
Józsi M, Licht C, Strobel S, Zipfel SHL, Richter H, Heinen S, Zipfel PF, Skerka C. Factor H autoantibodies in atypical hemolytic uremic syndrome correlate with CFHR1/CFHR3 deficiency. Blood. 2008 Feb 1;111(3):1512-4.
Józsi M, Strobel S, Dahse HM, Liu WS, Hoyer PF, Oppermann M, Skerka C, Zipfel PF. Anti-factor H autoantibodies block C-terminal recognition function of factor H in hemolytic uremic syndrome. Blood. 2007 Sep 1;110(5):1516-8.
Zipfel PF, Edey M, Heinen S, Józsi M, Richter H, Misselwitz J, Hoppe B, Routledge D, Strain L, Hughes AE, Goodship JA, Licht C, Goodship TH, Skerka C. Deletion of complement factor H-related genes CFHR1 and CFHR3 is associated with atypical hemolytic uremic syndrome. PLoS Genet. 2007 Mar 16;3(3):e41.
Józsi M, Oppermann M, Lambris JD, Zipfel PF. The C-terminus of complement factor H is essential for host cell protection. Mol Immunol. 2007 Apr;44(10):2697-2706.
Józsi M, Heinen S, Hartmann A, Ostrowicz C, Halbich S, Richter H, Kunert A, Licht C, Saunders RE, Perkins SJ, Zipfel PF, Skerka C. Factor H and Atypical Hemolytic Uremic Syndrome: Mutations in the C-terminus Cause Structural Changes and Defective Recognition Functions. J Am Soc Nephrol. 2006 Jan;17(1):170-7.
Józsi M, Richter H, Loschmann I, Skerka C, Buck F, Beisiegel U, Erdei A, Zipfel PF. FHR-4A: a new factor H-related protein is encoded by the human FHR-4 gene. Eur J Hum Genet. 2005, 13(3):321-329.
Manuelian T, Hellwage J, Meri S, Caprioli J, Noris M, Heinen S, Józsi M, Neumann HP, Remuzzi G, Zipfel PF. Mutations in factor H reduce binding affinity to C3b and heparin and surface attachment to endothelial cells in hemolytic uremic syndrome. J Clin Invest. 2003 Apr;111(8):1181-90.
Józsi M, Prechl J, Bajtay Z, Erdei A. Complement receptor type 1 (CD35) mediates inhibitory signals in human B lymphocytes. J Immunol. 2002 Mar 15;168(6):2782-8.

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