Skip to main content

Web Content Display Web Content Display

Kantyka Lab | Proteolysis and Post-translational Modification of Proteins

The essence of our research is the phenomenon of the formation of post-translational modifications

Web Content Display Web Content Display

Kantyka Lab | Proteolysis and Post-translational Modification of Proteins

Our scientific interests are focused on the posttranslational modifications (PTMs) of proteins and peptides, which coincide with infection, inflammation and development of civilization-related diseases.

Research objectives:

The underlying hypothesis is that PTMs impact the structure and activity of proteins and bioactive peptides. Our aim is to correlate PTMs with observed activity and structural changes in the pathophysiological context in the effort to delineate mechanisms of diseases development and to identify novel potential therapeutic targets. Although we focus on basic research, we always keep our sight on the pathophysiological importance of our findings and their applicability for translational developments.

Our efforts are orbit between three related subjects such as:

  • Human proteolytic enzymes in cell function regulation

Our research is concentrated on the analysis of human proteases – MMPs and kallikreins – involvement in cell and tissue function, development and progress of inflammation and their role in bacterial infections. We are focused on the epithelial tissue, which forms the first and arguably the most important barrier of defense against potentially deleterious external factors. Our research includes involvement of proteases in posttranslational processing of proteins during infection, wound healing, chronic inflammation and obesity.

  • Microbial proteases, their inhibitors and bacterial virulence factors

We aim of this group is to identify and analyze the bacterial virulence factors, which play a role in the development of the gum diseases. We are currently focused on the MMP activation during aspiration pneumon ia caused by oral microbiota. We are currently developing the research project to investigate the details of such activation. We are hoping, that this research will allow description of the novel mechanism of tissue degradation in bacterial lung infections and will translate to the into the new therapeutical strategies. This research is a broad collaboration with prof. Jan Potempa from nearby Faculty of Biochemistry, Biophysics and Biotechnology of our University.

  • Posttranslational modifications in the inflammatory diseases

We investigate the biological function of peptides and proteins modified as a result of the inflammatory reaction associated with RA, periodontitis, aspiration pneumonia or Sjogren’s syndrome. Research aims include analysis on how citrullination and carbamylation impact the immune system components, including antibacterial peptides, proteolytic cascades, antibodies and ECM proteins, in context of the pathological conditions. In addition to the basic research, the group is interested in identification and characterization of novel biomarkers associated with early subclinical stages of diseases development. We are currently leading the international GRIEG project, funded under NORWAY GRANTS initiative. Our major Norwegian partner is  Piotr Mydel, PhD, who supervises the investigations at University of Bergen in Norway.

Research techniques and equipment:

As a whole, the research group has a broad experience in expression and purification of recombinant and native human and bacterial proteins, their biochemical characterization, PTM analysis, including effects on biological functions of peptides and proteins. The core of the laboratory machine park encompasses several FPLC and HPLC chromatography systems and microscale thermophoresis (MST) analyzers, including Monolith NT.115 and Monolith NT.FreeLabel (both from NanoTemper Technologies).

Collaboration:

Our research embraces many collaborators, local (WBBiB UJ, Krakow University of Technology), national (Wroclaw university of Technology, Gdansk University) and international (Bremen, Barcelona, Aarhus, and many others), both academic and translational (Krakow University of Technology, WellnanoPharm) creating a truly interdisciplinary and international group very well linked, with high potentials to carry out ambitious research projects.

Research grants:

SONATA BIS: " Processing and posttranslational modifications of ghrelin - an appetite modulating peptide as the mechanistic link between prolonged inflammation, chronic bacterial infection and obesity development"

GRIEG: “Novel mechanisms of PAD activity regulation. Substrate specificity and activation of peptidyl arginine deiminase in the context of rheumatoid arthritis”

Tomasz Kantyka, PhD

Tomasz Kantyka, PhD

Read More o Tomasz Kantyka, PhD

Ewa Bielecka, PhD

Anna Maksylewicz, PhD

Łukasz Pijanowski, PhD

Grzegorz Bereta, PhD

Publications:

1: Miastkowska M, Kantyka T, Bielecka E, Kałucka U, Kamińska M, Kucharska M, Kilanowicz A, Cudzik D, Cudzik K. Enhanced Biological Activity of a Novel Preparation of Lavandula angustifolia Essential Oil. Molecules. 2021 Apr 23;26(9):2458. doi: 10.3390/molecules26092458. PMID: 33922508; PMCID: PMC8122903.


2: Milewska A, Falkowski K, Kulczycka M, Bielecka E, Naskalska A, Mak P, Lesner A, Ochman M, Urlik M, Diamandis E, Prassas I, Potempa J, Kantyka T, Pyrc K. Kallikrein 13 serves as a priming protease during infection by the human coronavirus HKU1. Sci Signal. 2020 Nov 24;13(659):eaba9902. doi: 10.1126/scisignal.aba9902. PMID: 33234691; PMCID: PMC7857416.


3: Sochalska M, Stańczyk MB, Użarowska M, Zubrzycka N, Kirschnek S, Grabiec AM, Kantyka T, Potempa J. Application of the In Vitro HoxB8 Model System to Characterize the Contributions of Neutrophil-LPS Interaction to Periodontal Disease. Pathogens. 2020 Jul 1;9(7):530. doi: 10.3390/pathogens9070530. PMID: 32630208; PMCID: PMC7399906.


4: Falkowski K, Bielecka E, Thøgersen IB, Bocheńska O, Płaza K, Kalińska M, Sąsiadek L, Magoch M, Pęcak A, Wiśniewska M, Gruba N, Wysocka M, Wojtysiak A, Brzezińska-Bodal M, Sychowska K, Pejkovska A, Rehders M, Butler G, Overall CM, Brix K, Dubin G, Lesner A, Kozik A, Enghild JJ, Potempa J, Kantyka T. Kallikrein-Related Peptidase 14 Activates Zymogens of Membrane Type Matrix Metalloproteinases (MT-MMPs)-A CleavEx Based Analysis. Int J Mol Sci. 2020 Jun 19;21(12):4383. doi: 10.3390/ijms21124383. PMID: 32575583; PMCID: PMC7352328.


5: Jonsson MK, Kantyka T, Falkowski K, Aliko A, Aga AB, Lillegraven S, Sexton J, Fevang BT, Mydel P, Haavardsholm EA. Peptidylarginine deiminase 4 (PAD4) activity in early rheumatoid arthritis. Scand J Rheumatol. 2020 Mar;49(2):87-95. doi: 10.1080/03009742.2019.1641216. Epub 2019 Sep 23. PMID: 31544586.


6: Kamińska M, Aliko A, Hellvard A, Bielecka E, Binder V, Marczyk A, Potempa J, Delaleu N, Kantyka T, Mydel P. Effects of statins on multispecies oral biofilm identify simvastatin as a drug candidate targeting Porphyromonas gingivalis. J Periodontol. 2019 Jun;90(6):637-646. doi: 10.1002/JPER.18-0179. Epub 2018 Dec 26. PMID: 30506795; PMCID: PMC6545270.


7: Aliko A, Kamińska M, Falkowski K, Bielecka E, Benedyk-Machaczka M, Malicki S, Kozieł J, Wong A, Bryzek D, Kantyka T, Mydel P. Discovery of Novel Potential Reversible Peptidyl Arginine Deiminase Inhibitor. Int J Mol Sci. 2019 May 2;20(9):2174. doi: 10.3390/ijms20092174. PMID: 31052493; PMCID: PMC6539144.


8: Gruba N, Bielecka E, Wysocka M, Wojtysiak A, Brzezińska-Bodal M, Sychowska K, Kalińska M, Magoch M, Pęcak A, Falkowski K, Wiśniewska M, Sąsiadek L, Płaza K, Kroll E, Pejkovska A, Rehders M, Brix K, Dubin G, Kantyka T, Potempa J, Lesner A. Development of Chemical Tools to Monitor Human Kallikrein 13 (KLK13) Activity. Int J Mol Sci. 2019 Mar 28;20(7):1557. doi: 10.3390/ijms20071557. PMID: 30925705; PMCID: PMC6479877.


9: Jentsch HFR, Arnold N, Richter V, Deschner J, Kantyka T, Eick S. Salivary, gingival crevicular fluid and serum levels of ghrelin and chemerin in patients with periodontitis and overweight. J Periodontal Res. 2017 Dec;52(6):1050-1057. doi: 10.1111/jre.12476. Epub 2017 Jun 20. PMID: 28631313.


10: Plaza K, Kalinska M, Bochenska O, Meyer-Hoffert U, Wu Z, Fischer J, Falkowski K, Sasiadek L, Bielecka E, Potempa B, Kozik A, Potempa J, Kantyka T. Gingipains of Porphyromonas gingivalis Affect the Stability and Function of Serine Protease Inhibitor of Kazal-type 6 (SPINK6), a Tissue Inhibitor of Human Kallikreins. J Biol Chem. 2016 Sep 2;291(36):18753-64. doi: 10.1074/jbc.M116.722942. Epub 2016 Jun 27. PMID: 27354280; PMCID: PMC5009250.


11: Laugisch O, Wong A, Sroka A, Kantyka T, Koziel J, Neuhaus K, Sculean A, Venables PJ, Potempa J, Möller B, Eick S. Citrullination in the periodontium--a possible link between periodontitis and rheumatoid arthritis. Clin Oral Investig. 2016 May;20(4):675-83. doi: 10.1007/s00784-015-1556-7. Epub 2015 Aug 13. PMID: 26264638; PMCID: PMC5146953.


12: Kalinska M, Meyer-Hoffert U, Kantyka T, Potempa J. Kallikreins - The melting pot of activity and function. Biochimie. 2016 Mar;122:270-82. doi: 10.1016/j.biochi.2015.09.023. Epub 2015 Sep 25. PMID: 26408415; PMCID: PMC4747678.


13: Goulas T, Mizgalska D, Garcia-Ferrer I, Kantyka T, Guevara T, Szmigielski B, Sroka A, Millán C, Usón I, Veillard F, Potempa B, Mydel P, Solà M, Potempa J, Gomis-Rüth FX. Structure and mechanism of a bacterial host-protein citrullinating virulence factor, Porphyromonas gingivalis peptidylarginine deiminase. Sci Rep. 2015 Jul 1;5:11969. doi: 10.1038/srep11969. PMID: 26132828; PMCID: PMC4487231.


14: Bielecka E, Scavenius C, Kantyka T, Jusko M, Mizgalska D, Szmigielski B, Potempa B, Enghild JJ, Prossnitz ER, Blom AM, Potempa J. Peptidyl arginine deiminase from Porphyromonas gingivalis abolishes anaphylatoxin C5a activity. J Biol Chem. 2014 Nov 21;289(47):32481-7. doi: 10.1074/jbc.C114.617142. Epub 2014 Oct 16. PMID: 25324545; PMCID: PMC4239603.


15: Eick S, Puklo M, Adamowicz K, Kantyka T, Hiemstra P, Stennicke H, Guentsch A, Schacher B, Eickholz P, Potempa J. Lack of cathelicidin processing in Papillon-Lefèvre syndrome patients reveals essential role of LL-37 in periodontal homeostasis. Orphanet J Rare Dis. 2014 Sep 27;9:148. doi: 10.1186/s13023-014-0148-y. PMID: 25260376; PMCID: PMC4181722.


16: Koziel J, Bryzek D, Sroka A, Maresz K, Glowczyk I, Bielecka E, Kantyka T, Pyrć K, Svoboda P, Pohl J, Potempa J. Citrullination alters immunomodulatory function of LL-37 essential for prevention of endotoxin-induced sepsis. J Immunol. 2014 Jun 1;192(11):5363-72. doi: 10.4049/jimmunol.1303062. Epub 2014 Apr 25. PMID: 24771854; PMCID: PMC4036085.


17: Fischer J, Wu Z, Kantyka T, Sperrhacke M, Dimitrieva O, Koblyakova Y, Ahrens K, Graumann N, Baurecht H, Reiss K, Schröder JM, Proksch E, Meyer-Hoffert U. Characterization of Spink6 in mouse skin: the conserved inhibitor of kallikrein- related peptidases is reduced by barrier injury. J Invest Dermatol. 2014 May;134(5):1305-1312. doi: 10.1038/jid.2013.502. Epub 2013 Nov 22. PMID: 24352040.


18: Jusko M, Potempa J, Kantyka T, Bielecka E, Miller HK, Kalinska M, Dubin G, Garred P, Shaw LN, Blom AM. Staphylococcal proteases aid in evasion of the human complement system. J Innate Immun. 2014;6(1):31-46. doi: 10.1159/000351458. Epub 2013 Jul 3. PMID: 23838186; PMCID: PMC3972074.


19: Fröhlich E, Kantyka T, Plaza K, Schmidt KH, Pfister W, Potempa J, Eick S. Benzamidine derivatives inhibit the virulence of Porphyromonas gingivalis. Mol Oral Microbiol. 2013 Jun;28(3):192-203. doi: 10.1111/omi.12015. Epub 2012 Dec 26. PMID: 23279840; PMCID: PMC3620930.


20: Kantyka T, Pyrc K, Gruca M, Smagur J, Plaza K, Guzik K, Zeglen S, Ochman M, Potempa J. Staphylococcus aureus proteases degrade lung surfactant protein A potentially impairing innate immunity of the lung. J Innate Immun. 2013;5(3):251-60. doi: 10.1159/000345417. Epub 2012 Dec 11. PMID: 23235402; PMCID: PMC3787703.


21: Laugisch O, Schacht M, Guentsch A, Kantyka T, Sroka A, Stennicke HR, Pfister W, Sculean A, Potempa J, Eick S. Periodontal pathogens affect the level of protease inhibitors in gingival crevicular fluid. Mol Oral Microbiol. 2012 Feb;27(1):45-56. doi: 10.1111/j.2041-1014.2011.00631.x. Epub 2011 Dec 7. PMID: 22230465; PMCID: PMC3257822.


22: Kalińska M, Kantyka T, Greenbaum DC, Larsen KS, Władyka B, Jabaiah A, Bogyo M, Daugherty PS, Wysocka M, Jaros M, Lesner A, Rolka K, Schaschke N, Stennicke H, Dubin A, Potempa J, Dubin G. Substrate specificity of Staphylococcus aureus cysteine proteases--Staphopains A, B and C. Biochimie. 2012 Feb;94(2):318-27. doi: 10.1016/j.biochi.2011.07.020. Epub 2011 Jul 23. PMID: 21802486.


23: Kulig P, Kantyka T, Zabel BA, Banas M, Chyra A, Stefanska A, Tu H, Allen SJ, Handel TM, Kozik A, Potempa J, Butcher EC, Cichy J. Regulation of chemerin chemoattractant and antibacterial activity by human cysteine cathepsins. J Immunol. 2011 Aug 1;187(3):1403-10. doi: 10.4049/jimmunol.1002352. Epub 2011 Jun 29. PMID: 21715684; PMCID: PMC3140563.


24: Kantyka T, Fischer J, Wu Z, Declercq W, Reiss K, Schröder JM, Meyer-Hoffert U. Inhibition of kallikrein-related peptidases by the serine protease inhibitor of Kazal-type 6. Peptides. 2011 Jun;32(6):1187-92. doi: 10.1016/j.peptides.2011.03.009. Epub 2011 Mar 23. PMID: 21439340.


25: Kantyka T, Plaza K, Koziel J, Florczyk D, Stennicke HR, Thogersen IB, Enghild JJ, Silverman GA, Pak SC, Potempa J. Inhibition of Staphylococcus aureus cysteine proteases by human serpin potentially limits staphylococcal virulence. Biol Chem. 2011 May;392(5):483-9. doi: 10.1515/BC.2011.044. PMID: 21476872; PMCID: PMC4372843.


26: Wladyka B, Kozik AJ, Bukowski M, Rojowska A, Kantyka T, Dubin G, Dubin A. α1-Antichymotrypsin inactivates staphylococcal cysteine protease in cross-class inhibition. Biochimie. 2011 May;93(5):948-53. doi: 10.1016/j.biochi.2011.01.014. Epub 2011 Feb 3. PMID: 21296644.


27: Kantyka T, Potempa J. Human SCCA serpins inhibit staphylococcal cysteine proteases by forming classic "serpin-like" covalent complexes. Methods Enzymol. 2011;499:331-45. doi: 10.1016/B978-0-12-386471-0.00016-X. PMID: 21683261.


28: Kantyka T, Shaw LN, Potempa J. Papain-like proteases of Staphylococcus aureus. Adv Exp Med Biol. 2011;712:1-14. doi: 10.1007/978-1-4419-8414-2_1. PMID: 21660655.


29: Kantyka T, Rawlings ND, Potempa J. Prokaryote-derived protein inhibitors of peptidases: A sketchy occurrence and mostly unknown function. Biochimie. 2010 Nov;92(11):1644-56. doi: 10.1016/j.biochi.2010.06.004. Epub 2010 Jun 14. PMID: 20558234; PMCID: PMC2952067.


30: Meyer-Hoffert U, Wu Z, Kantyka T, Fischer J, Latendorf T, Hansmann B, Bartels J, He Y, Gläser R, Schröder JM. Isolation of SPINK6 in human skin: selective inhibitor of kallikrein-related peptidases. J Biol Chem. 2010 Oct 15;285(42):32174-81. doi: 10.1074/jbc.M109.091850. Epub 2010 Jul 28. PMID: 20667819; PMCID: PMC2952218.


31: Karim AY, Kulczycka M, Kantyka T, Dubin G, Jabaiah A, Daugherty PS, Thogersen IB, Enghild JJ, Nguyen KA, Potempa J. A novel matrix metalloprotease- like enzyme (karilysin) of the periodontal pathogen Tannerella forsythia ATCC 43037. Biol Chem. 2010 Jan;391(1):105-17. doi: 10.1515/BC.2010.009. PMID: 19919176; PMCID: PMC2884989.


32: Kantyka T, Latendorf T, Wiedow O, Bartels J, Gläser R, Dubin G, Schröder JM, Potempa J, Meyer-Hoffert U. Elafin is specifically inactivated by RgpB from Porphyromonas gingivalis by distinct proteolytic cleavage. Biol Chem. 2009 Dec;390(12):1313-20. doi: 10.1515/BC.2009.136. PMID: 19747076; PMCID: PMC2795110.


33: Smagur J, Guzik K, Bzowska M, Kuzak M, Zarebski M, Kantyka T, Walski M, Gajkowska B, Potempa J. Staphylococcal cysteine protease staphopain B (SspB) induces rapid engulfment of human neutrophils and monocytes by macrophages. Biol Chem. 2009 Apr;390(4):361-71. doi: 10.1515/BC.2009.042. PMID: 19284294.


34: Potempa M, Potempa J, Kantyka T, Nguyen KA, Wawrzonek K, Manandhar SP, Popadiak K, Riesbeck K, Eick S, Blom AM. Interpain A, a cysteine proteinase from Prevotella intermedia, inhibits complement by degrading complement factor C3. PLoS Pathog. 2009 Feb;5(2):e1000316. doi: 10.1371/journal.ppat.1000316. Epub 2009 Feb 27. Erratum in: PLoS Pathog. 2009 Mar;5(3). doi: 10.1371/annotation/e82f810e-738a-47e5-9295-5a0cc9a0dc6c. PMID: 19247445; PMCID: PMC2642729.


35: Dubin G, Stec-Niemczyk J, Kisielewska M, Pustelny K, Popowicz GM, Bista M, Kantyka T, Boulware KT, Stennicke HR, Czarna A, Phopaisarn M, Daugherty PS, Thøgersen IB, Enghild JJ, Thornberry N, Dubin A, Potempa J. Enzymatic activity of the Staphylococcus aureus SplB serine protease is induced by substrates containing the sequence Trp-Glu-Leu-Gln. J Mol Biol. 2008 May 30;379(2):343-56. doi: 10.1016/j.jmb.2008.03.059. Epub 2008 Apr 3. PMID: 18448121.


36: Mallorquí-Fernández N, Manandhar SP, Mallorquí-Fernández G, Usón I, Wawrzonek K, Kantyka T, Solà M, Thøgersen IB, Enghild JJ, Potempa J, Gomis-Rüth FX. A new autocatalytic activation mechanism for cysteine proteases revealed by Prevotella intermedia interpain A. J Biol Chem. 2008 Feb 1;283(5):2871-82. doi: 10.1074/jbc.M708481200. Epub 2007 Nov 9. PMID: 17993455; PMCID: PMC2772895.