A Szentágothai János Kutatóközpont a PTE korszerű, nemzetközi tudományszervezési és menedzsment normák szerint kialakított új intézménye, amely az élettudományi, élettelen természettudományi, valamint környezettudományi oktatás...
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.
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 4. Circulation114(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 model. Circulation116(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 J, Hinkel R, Pfosser A, Wuchrer A, Trenkwalder T, Stachel G, Hatzopoulos A, Bock-Marquette I, DiMaio M, Kupatt C. Resolution 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 T, Hinkel R, Pfosser A, Sultana S, Stachel G, Lebherz C, Bock-Marquette I, Deindl E, Kupatt 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 R, Pfosser A, Stachel G, Schroeder M, Trenkwalder T, Lebherz C, Boekstegers P, Bock-Marquette I, Di-Maio MJ, Kupatt 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 R, Trenkwalder T, Pfosser A, Stachel G, Lebherz C, Bock-Marquette I, Deindl L, DiMaio M, Kupatt 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 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. 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 R, Trenkwalder T, Pfosser A, Globisch F, Stachel G, Lebherz C, Bock-Marquette I, Kupatt 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
