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A Szentágothai János Kutatóközpont a PTE korszerű, nemzetközi tudományszervezési és menedzsment normák szerint kialakított új intézménye, amely az élettudományi, élettelen természettudományi, valamint környezettudományi oktatás...

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Regenerative Science, Sport and Medicine Research Group

  • Research concept
  • Members
  • Publications
  • Awarded projects
  • R and D results
  • Services
  • Laboratories, instruments
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  • Student awards

The primary focus of our research team is to reveal and investigate molecules and pathways critical for organ regeneration and repair in humans.

Our pursuit embraces a wide spectrum of research areas such as regenerative science, sport and medicine where the fields are conjoint in a three dimensional approach: health. The umbrella term regenerative medicine covers the rejuvenation of the heart, traumatized outer/inner ear, skeletal muscle and tendons. Sport reflects the complex spectrum of biochemical processes during physical exercise and mental stress supporting a search for novel drug candidates associated with regenerative medicine. Thus, a translational approach of enhancing quality of life by understanding the very concept of regeneration is at the epicenter of our program.

Heart disease is the predominant cause of disability and death in industrialized nations of the world. Although more commonly affecting adults, heart disease in children is also the leading non-infectious cause of death in the first year of life and often involves abnormalities in cardiac cell specification, migration and survival. Since the heart is incapable of sufficient regeneration, immense efforts have been devoted to promote cardiac repair. Use of stem cells to repopulate damaged cardiac tissue is promising, but is currently limited by technical considerations. As an alternative approach we hypothesize utilizing small, secreted molecules may be a potential alternative to stimulate regeneration, averting technical hurdles associated with stem cell therapy applications. Previously we discovered, external administration of Thymosin beta-4 (TB4), a 43 amino acid peptide and its four amino acid C-terminal variable domain promote myocardial cell migration and survival in embryonic tissues in vitro, and retain this property after birth (Bock-Marquette, I. et al. Nature. 432, 466-72. 2004; Bock-Marquette I. et al. JMCC. 87:113-125. 2015). With the discovery of TB4’s regenerative capacities, we hypothesize additional organs and tissues might react equally to the peptide or to its domain combinations following injury. Accordingly, tissues, like tendons and the tympanic membrane are being currently tested for regenerative purposes. In collaboration with Dr. Tibor Mintal, traumatized tendons are replaced and regenerated by a new method utilizing cadaver grafts. To avoid immunogenic or necrotic reactions in the host, we utilize a process called decellularization. The process eliminates cells in the postmortem tissue whilst keeping the extracellular matrix (ECM). The host ECM acts as a scaffold for progenitor cells and special peptides to inhabit, thereby creating a host-friendly environment. In collaboration with Dr. Peter Bako we are currently testing the effect of TB4 on tympanic membrane repair. Our ultimate goal is to extend our focus on the injuries of the inner ear. Moreover, in collaboration with Dr. Szilard Rendeki, we are analyzing the molecular alterations initiated by blunt chest injuries in a rodent model and in humans. We predict to identify novel molecular markers to support clinical diagnosis and treatment of lung traumas.  Simultaneously, mesenchymal stem cell transformation into human cardiac myocytes utilizing our identified potential peptides is currently being tested. Micropeptides and CRISPR technology are on the verge of R&D.

Sport, as physical activity plays a vital role in improving the quality of life. Numerous studies and common sense support this hypothesis. Identification of potential exercise-initiated small molecules in support of organ regeneration and repair in humans is aimed to discover complex physiological, psychological and biochemical responses due to extreme and recreational physical load. Our results indicate protein expression profile is indeed significantly altered in human blood plasma and saliva samples following physical and/or psychological stress. Our investigations are supported by new generation sequencing (NGS), 2D-electrophoresis and mass spectrometry analyses and resulted in identification of numerous promising protein candidates for clinical utilization.

Finally, beside organ regeneration, there is an additional special component to our research team. A novel, multi-level early-stage screening program for lung cancer, a leading cause of death within cancerous mortality was developed and transcribed into a national public health program via a law proposal. The proposal supports early, cost-efficient means of public health initiative greatly reducing mortality whilst improving quality of life, workforce and subsequently national GDP.



Dr Gallyas Ferenc
professor

Dr. Anikó Takátsy
associate professor
aniko.takatsy@aok.pte.hu
Dr. Antal Tapodi
assistant professor
Antal.Tapodi@aok.pte.hu
+36 72 536001 /31656
Dr Maar Klaudia
PhD student

Szabolcs Maár
PhD student

Faskerti Gabor
PhD student

Heléna Halász
laboratory technician

Dr Krisztian Eros
assistant research fellow

Dr Roland Hetenyi
PhD student

Matyas Rendeki
student

Yorgen Kosberg
student

Marvin Bungenstock
student

Lilla Czuni
PhD student

Péter Urbán
assistant research fellow
urban.peter@pte.hu
29291
Dr Zsofia Nagy
PhD student

Dr Gergely Novogradecz


Dr Jazmin Nagy
student

Balint Lippai
student

Dr Szilard Rendeki
assistant professor

Dr Peter Bako
associate professor

Dr Tibor Mintal
assistant professor

1. Kispal G., Sumegi B., Dietmeier K., Bock I., Gajdos G., Tomcsanyi T., Sandor A. Cloning and sequencing of a cDNA encoding Saccharomyces cerevisiae carnitine acetyltransferase. Use of the cDNA in gene disruption studies. J Biol Chem.268(3):1824-9. (1993). IF:5.328

2. Melegh B., Pap M., Bock I., Rebouche C.J. Relationship of carnitine and carnitine precursors lysine, epsilon-N-trimethyllysine, and gamma-butyrobetaine in drug-induced carnitine depletion. Pediatr Res. 34(4):460-4. (1993). IF: 2.607

3. Melegh, B., Molnar, D., Masszi, G., Bock, I., Kopcsanyi, G., Pap, M. Effect of pivampicillin treatment on metabolic fuel consumption. Pediatr Res.35:284 (1994). IF: 2.607

4.Melegh, B., Harangi, F., Bock, I., Szucs, L. Carnitine dependent changes of plasma levels and urinary output of amino acids in pivampicillin treatment. Acta Ped Hun.34:87-98 (1994). IF:1.768

5. Burus, I., Bock, I., Melegh, B. Role of chromatography in the diagnosis of certain congenital metabolic diseases. Clin Exp Lab Med.(Budapest) 22:167 (1995).

6. Melegh, B., Bock, I., Burus, I., Szekely, G., Douglas, A., Gage, D. A., Sherry, A. D., Bieber, L. L. Problems of regulation of biosynthesis of carnitine. Clin Exp Lab Med.(Budapest) 22:151 (1995).

7. Bock, I., Melegh, B. Diagnosis of intron 22 inversions in hemophilia A. Clin Exp Lab Med. (Budapest) 22:137 (1995).

8. Burus, I., Melegh, B., Bock, I., Dani, M., Acsadi, G., Kosztolanyi, G., Mehes, K. Gene deletion analysis of Duchenne muscular dystrophy with multiplex exon amplification. Orv Hetil.136:545-547 (1995).

9. Melegh B., Seress L., Sumegi B., Trombitas K., Bock I., Kispal G., Olah E., Mehes K. Mitochondrial DNA deletion in hereditary cardio-encephalo-myopathy Orv Hetil.136(24):1275-9. (1995).

10. Bock I., Melegh B., Nagy A., Losonczy H., Csete B., Schroder W., Kardos M., Istvan L., Jager R., Toth A.M., Toth A., Falko H., Mozsik G. Molecular biologic study and the factor VIII gene in hemophilia A.  Orv Hetil.137(46):2573-5. (1996).

11. Farkas V., Bock I., Cseko J., Sandor A. Inhibition of carnitine biosynthesis by valproic acid in rats--the biochemical mechanism of inhibition. Biochem Pharmacol.52(9):1429-33. (1996). IF:4.254

12. Melegh B., Bock I., Gati I., Mehes K. Multiple mitochondrial DNA deletions and persistent hyperthermia in a patient with Brachmann-de Lange phenotype. Am J Med Genet.65(1):82-8. (1996). IF:4.562

13. Melegh B., Hermann R., Bock I. Generation of hydroxytrimethyllysine from trimethyllysine limits the carnitine biosynthesis in premature infants. Acta Paediatr. 85(3):345-50. (1996). IF:1.768

14. Danko I., Williams P., Herweijer H., Zhang G., Latendresse J.S., Bock I., Wolff J.A. High expression of naked plasmid DNA in muscles of young rodents. Hum Mol Genet. 6(9):1435-43. (1997). IF: 7.386

15.Sokoloff A.V., Bock I., Zhang G., Sebestyen M.G., Wolff J.A. The interactions of peptides with the innate immune system studied with use of T7 phage peptide display. Mol Ther.2(2):131-9. (2000). IF:6.873

16. Sokoloff A.V., Bock I., Zhang G., Hoffman S., Dama J., Ludtke J.J., Cooke A.M., Wolff J.A. Specific recognition of protein carboxy-terminal sequences by natural IgM antibodies in normal serum. Mol Ther. (6):821-30. (2001). IF:6.873

17. Bock-Marquette I., Saxena A., White M.D., Dimaio J.M., Srivastava D..Thymosin beta-4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair. Nature.432(7016):466-72. (2004). IF:34.48

18. Hinkel R, Horstkotte J ,Olson T, El Aouni C, Muller S, Mayer S, Bock-Marquette I, Hatzopoulos A, Boekstegers P, Kupatt C. Rapid eEPC-mediated cardioprotection after ischemia/reperfusion: Role of Thymosin beta 4Circulation114(18):238-238S (2006).IF:14.816

19. Srivastava D, Saxena A, Dimaio JM, Bock-Marquette I. Thymosin beta4 is Cardioprotective After Myocardial Infarction. Ann. N. Y. Acad. Sci.. 1112:161-70.(2007). IF:3.155

20. Hinkel R, Olson T, Horstkotte J, El Aouri C, Mueller S, Mayer S, Bock-Marquette I, DiMaio M, Hatzopoulos A, Boekstegers P, Kupatt C. Cardioprotective potential of thymosin 64 after ischemia/reperfusion in a preclinical pig modelCirculation116(16):130-130S (2007). IF:14.816

21. Hinkel, R., El-Aouni, C., Olson, T., Horstkotte, J., Müller, S., Müller, S., Willhauck, M., Spitzweg, C., Gildehaus, F.J., Bock-Marquette, I., DiMaio, J.M., Hatzopoulos, A., Boekstegers, P., Kupatt C. Thymosin ß4 is an essential paracrine mediator of embryonic endothelial progenitor cell derived cardioprotection. Circulation.117(17);2232-40.(2008). IF:14.816

22. Kupatt C., Bock-Marquette I., Boekstegers P. Embryonic Endothelial Progenitor Cell-Mediated Cardioprotection requires Thymosin beta4. TrendsCardiovascMed.18(6):205-10. (2008) IF:4.367

23. Bock-Marquette I., Shrivastava S., Pipes JCT.,Thatcher JE, Blystone A., Shelton JM, Galindo CL., Melegh B., Srivastava D., Olson, EN., DiMaio JM. Thymosin b4 mediated PKC activation is essential to initiate the embryonic coronary developmental program and epicardial progenitor cell activation in adult mice in vivo. JMCC.46(5):728-738 (2009). IF:5.166

24.Horstkotte JHinkel RPfosser AWuchrer ATrenkwalder TStachel GHatzopoulos ABock-Marquette IDiMaio MKupatt CResolution of chronic ischemia by regional application of emrbyonic eEPCs and thymosin B4 in preclinical animal models.J Vasc Res46:31S3(2009). IF:2.895

25. Trenkwalder THinkel RPfosser ASultana SStachel GLebherz CBock-Marquette IDeindl EKupatt C. Enhanced therapeutic neovascularisation using AAV2/9 based gene transfer of Thymosin beta 4 and the role of Protein Kinase B Activation J Vasc Res46:26S3 (2009). IF:2.651

26.Hinkel RPfosser AStachel GSchroeder MTrenkwalder TLebherz CBoekstegers PBock-Marquette IDi-Maio MJKupatt C. Therapeutic Neovascularization by AAV2/9 Based Gene Transfer of Thymosin beta 4 in a Chronic Ischemic Hindlimb Model. Molecular Therapy17:S347 (2009). IF:6.239

27.Hinkel RTrenkwalder TPfosser AStachel GLebherz CBock-Marquette IDeindl LDiMaio MKupatt C. Enhanced therapeutic neovascularization by AAV 2/9 based gene transfer of thymosin beat4: the role of protein kinase B activation.Human Gene Therapy20(11):1458-1458 (2009). IF:4.202

28. Hinkel R, Bock-Marquette I, Kupatt C. Thymosin beta 4 induced neovascularization: how gene therapy may complement cell therapy. Human Gene Therapy20(11):1362-1363 (2009). IF:4.202

29.Hinkel R,Bock-Marquette IHazopoulos AKKupatt CThymosin beta 4: a key factor for protective effects of eEPCs in acute and chronic ischemia Ann. NY. A. S. 1194:105-111 (2010). IF:3.155

30. Shrivastava S., Srivastava D., Olson, EN., DiMaio J.M. and Bock-Marquette I. Thymosin b4 and cardiac repair - reminding the adult heart on its embryonic state. Ann. NY. A. S.1194:87-96 (2010). IF:3.155

31.Hinkel RTrenkwalder TPfosser AGlobisch FStachel GLebherz CBock-Marquette IKupatt C. Therapeutic neovascularization via Thymosin beta4 overexpression requires AKT activation and capillary sprouting in the calf muscles: evidence for backward signaling. Cardiovasc Res87:S59 (2010). IF:5.801

32.Hinkel R, Trenkwalder T, Gottlieb E, Pfosser A, Sultana S, Globisch F, Stachel G, Lebherz C, Bock-Marquette I, Kupatt C. AAV2.9 Thymosin beta 4 Regional Application Enhances Therapeutic Neovascularization and Requires AKT Activation and Capillary Sprouting in the Calf Muscle. Human Gene Therapy21(9):1202-1203 (2010). IF:4.202

33. Hinkel R, Wuchrer A, Horstkotte JC, Lebherz C, Hatzopoulos AK, Bock-Marquette I, DiMaio M, Boekstegers P, Kupatt C. Resolution of Chronic Ischemia by Regional Application of Embryonic eEPCs or Thymosin beta 4 in a Preclinical Pig Model Human Gene Therapy21(9):1199 (2010).IF:4.202

34. Trenkwalder T, Hinkel R, Sultana S, Stachel G, Pfosser A, Lebherz C, Bock-Marquette I, Deindl E, Kupatt C. Enhanced Therapeutic Neovascularization via AAV2.9/Thymosin beta 4: Evidence for a Myovascular Crosstalk. Human Gene Therapy21(9):1182 (2010). IF:4.202

35. Hinkel R, Bock-Marquette I, Hazopoulos AK, Kupatt C. Thymosin beta 4: a key factor for protective effects of eEPCs in acute and chronic ischemia. Ann. NY. A. S.1205:284-286 (2010). IF:3.155

36.Trenkwalder, T.; Hinkel, R.; Di, Q.; Bock-Marquette I., et al. rAAV 2.9 transmitted overexpression of thymosin beta 4 enhances neovascularisation in chronic ischemia via isoform specific PI3-Kinase activity J. Vasc. Res.48:1: 284 (2011). IF: 2.895

37.Hinkel, R., Husada, H., Trenkwalder, T., Di, Q., Lee, S., Petersen, B., Bock-Marquette, I., Niemann, H., Di Maio, M., Kupatt, C. Therapeutic neovascularization by AAV2/9-based gene transfer of Thymosin B4: results of a preclinical pig study. Cardiovasc. Res. 93:1: S117-S117(2012). IF: 6.064

38.Gesenhues, F.,Trenkwalder, T., Hinkel, R., Pfosser, A., Sultana, S., Globisch, F., Stachel, G., Lebherz C., Bock-Marquette, I., Kupatt, C. Thymosin beta 4 induced capillary sprouting in the calf muscles mediates therapeutic neovascularization - evidence for backward signalling. J. Vasc. Res.48:1: 185 (2011). IF: 2.651

39.Husada, W., Hinkel, R., J Horstkotte, J., Gottlieb, E., Trenkwalder, T., Di, Q., Lebherz, C., Bock-Marquette, I., Dimaio, M., Kupatt, C. Therapeutic neovascularization promoted by Thymosin beta 4 in a porcine model of chronic ischemia.J. Vasc. Res.  48:1:283-283 (2011). IF:2.651

40. Hinkel R, Trenkwalder T, Petersen B, Husada W, Gesenhues F, Lee S, Hannappel E, Bock-Marquette I, Theisen D, Leitner L, Boekstegers P, Cierniewski C, Müller OJ, le Noble F, Adams RH, Weinl C, Nordheim A, Reichart B, Weber C, Olson E, Posern G, Deindl E, Niemann H, Kupatt C. MRTF-A controls vessel growth and maturation by increasing the expression of CCN1 and CCN2. Nat. Commun.Jun 9;5:3970 (2014). IF:11.88 Q1

41. Hinkel R, Ball HL, DiMaio JM, Shrivastava S, Thatcher JE, Singh AN, Sun X, Faskerti G, Olson EN, Kupatt C and Bock-Marquette I.C-terminal AGES domain of Thymosin b4 promotes post-ischemic cardiac function and repairJMCC. (2015) Aug 5;87:113-125. IF:5.218 Q1

42. Földes F, Madai M, Németh V, Zana B, Papp H, Kemenesi G, Bock-Marquette I, Horváth G, Herczeg R, Jakab F. Serologic survey of the Crimean-Congo haemorrhagic fever virus infection among wild rodents in Hungary. Ticks Tick Borne Dis. (2019) Oct;10(6):101258. doi: 10.1016/j.ttbdis.2019.07.002. Epub (2019) IF: 3.055 Q1

2017 – 2018    Centre of Scientific Excellence Award 

2017 – 2021    GINOP 2.3.2 Award 

2013 – 2018    OTKA-K Award 

2013 – 2014    Szentagothai Advanced Scientist Award 

2010 – NIH, National Heart, Lung and Blood Institute Progenitor Cell Biology Consortium Harvard-UT Southwestern Research Hub 

2007 – 2010    NIH Mentored Clinical Scientist Development Award (K08)

2006 – 2008    AHA Texas Affiliate Beginning Grant-in-Aid Award 

2006 – 2007    Ted Nash Long Life Foundation Award 

Patents:

2010                Use of small peptides to promote tissue regeneration

2004                Method of treating, preventing, inhibiting or reducing damage to cardiac tissue

N/A

N/A

2020 Hetényi Roland TDK 1st place

2017 Hetenyi Roland  TDK 3rd place

CONTACT
Dr. Bock-Marquette Ildikó
Research Group Leader