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Csaba Szabo (pharmacologist)

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Csaba Szabo, a physician and pharmacologist, is the Head of the Pharmacology Section of the University of Fribourg in Switzerland.[1] The Public Library of Science Magazine, PLOS Biology, recognized Szabo in 2019 as one of the most cited researchers in the world.[2]

Early life

Szabo was born in Győr, Hungary on July 12, 1967. He received his M.D. from the Semmelweis University Medical School in Budapest in 1992. From 1992 to 1994 he trained in pharmacology at the William Harvey Institute in London with Nobel Laureate Sir John Vane[3] and received a Ph.D. in pharmacology. Szabo also holds a Ph.D. in physiology, and a Doctor of Sciences degree from the Hungarian University of Sciences.[4] From 2018 he serves as the Chair of the Pharmacology Section at the University of Fribourg, Switzerland.[1]

Research

Szabo’s research investigates the biological roles of small diffusible, labile gaseous molecules (gasotransmitters) in health and disease. His early work focused on the role of the gaseous mediator nitric oxide (a small diffusible biological mediator produced by nitric oxide synthases) in the blood vessel dysfunction and organ injury associated with circulatory shock. In addition to unveiling a new pathophysiological concept, this work also yielded new pharmacological tools, such as selective inhibitors of the inducible isoform of nitric oxide synthase.[5][6]

Subsequent work conducted by Szabo and his collaborators in the early 2000’s defined the role of a labile reactive species called peroxynitrite – formed by the reaction of superoxide and nitric oxide – in various disease states, including circulatory shock,[7] inflammation,[8] and the complications of diabetes.[9] In particular, these studies demonstrated that peroxynitrite induces breaks in the strands of the genetic material, DNA, which activate poly (ADP-ribose) polymerase (PARP), a mammalian nuclear and mitochondrial enzyme, which, in turn, induces cell necrosis, promotes inflammation and impairs vascular reactivity in various diseases.[10][11][12] He is currently spearheading an effort to repurpose clinically used inhibitors of PARP – which are currently only used in cancer therapy – for the experimental therapy of non-oncological diseases, such as circulatory shock and acute lung failure.[13]

Since 2007 Szabo’s research interest expanded into the roles of hydrogen sulfide (another gaseous biological mediator) in health and disease. His work identified novel roles of hydrogen sulfide as a mitigator of heart damage during heart attacks,[14] as a stimulator of new blood vessel formation,[15] as a protector of blood vessels during diabetes,[16] and as a stimulator of the cellular bioenergetics of mammalian cells.[17]

In the context of disease pathogenesis, in 2013, while at the University of Texas, he discovered that colon cancer cells upregulate hydrogen sulfide biosynthesis in order to stimulate their growth, promote tumor blood vessel formation and to resist chemotherapy.[18][19] In 2018 Szabo and his collaborators also demonstrated that bacterially-produced hydrogen sulfide protects the bacteria against immune-cell-mediated elimination.[20] In 2019 Szabo’s group in Fribourg, Switzerland experimentally proved the “Kamoun Hypothesis”,[21] and demonstrated that excessive generation of hydrogen sulfide leads to the metabolic inhibition and synaptic dysfunction of neurons in Down syndrome.[22][23]

In 1996 he co-founded a company called Inotek and served as its Chief Scientific Officer. The company focused on the development of various novel small molecules, including new inhibitors of PARP.[24] One of the compounds discovered by Inotek, PJ34, is a commonly used experimental tool to inhibit PARP.[25] Another, PARP inhibitor, INO-1001, entered clinical trials and Inotek partnered its development with Genentech in 2006.[26] In 2021, Szabo’s team demonstrated that low concentrations of the gaseous molecule cyanide – previously known only for its toxic effects – at ultra-low concentrations, can also have beneficial, i.e. stimulatory bioenergetic effects in mammalian cells,[27] thereby raising the possibility of cyanide being the fourth mammalian gaseous transmitter after nitric oxide, carbon monoxide and hydrogen sulfide.[28]

Awards & Honors

  • Novartis Prize of the British Pharmacological Society, 2003.[3]
  • Dennis Gabor Innovation Award, 2004.[29]
  • Officer's Cross - Order of Merit Award of the Hungarian Republic, 2006.[30]
  • Texas Star Award - University of Texas System.
  • Elected Fellow of the British Pharmacological Society, 2012.
  • Recognized as one of the most cited researchers, listed among the top 1,000 worldwide, PLOS Biology,
  • John Vane Medal or the British Pharmacological Society, 2021.
  • Highly Cited Researcher in Pharmacology, 2022.[31]

Publications

Szabo authored or co-authored over 500 publications, which were cited over 75,000 times, yielding a H-index of 140.[32]

Books

  • Cell Death: the role of PARP, 2000 (Taylor Francis).[33]
  • Adenosine Receptors, 2006 (Taylor Francis).[34]
  • Biomolecules, Section Editor-In-Chief.[35]

References

  1. ^ a b "Csaba Szabo | Abteilung Medizin | Universität Freiburg". www.unifr.ch. Retrieved 2022-05-24.
  2. ^ Baas, Jeroen (2019-07-06), "Bibliometrics", Supplementary data tables for "A standardized citation metrics author database annotated for scientific field" (PLoS Biology 2019), vol. 1, John P.A. Ioannidis, Richard Klavans, Kevin Boyack, Mendeley, doi:10.17632/btchxktzyw.1, retrieved 2022-05-24
  3. ^ a b e311-88a7-001dd8b721a7 "bps.ac.uk". {{cite web}}: Check |url= value (help)
  4. ^ "Köztestületi tagok". mta.hu (in Hungarian). Retrieved 2022-05-24.
  5. ^ Szabó, Csaba; Mitchell, Jane A.; Thiemermann, Christoph; Vane, John R. (March 1993). "Nitric oxide-mediated hyporeactivity to noradrenaline precedes the induction of nitric oxide synthase in endotoxin shock". British Journal of Pharmacology. 108 (3): 786–792. doi:10.1111/j.1476-5381.1993.tb12879.x. PMC 1908041. PMID 7682137.
  6. ^ Szabó, C; Southan, G J; Thiemermann, C (1994-12-20). "Beneficial effects and improved survival in rodent models of septic shock with S-methylisothiourea sulfate, a potent and selective inhibitor of inducible nitric oxide synthase". Proceedings of the National Academy of Sciences. 91 (26): 12472–12476. Bibcode:1994PNAS...9112472S. doi:10.1073/pnas.91.26.12472. ISSN 0027-8424. PMC 45460. PMID 7528923.
  7. ^ Zingarelli, Basilia; Day, Brian J; Crapo, James D; Salzman, Andrew L; Szabó, Csaba (January 1997). "The potential role of peroxynitrite in the vascular contractile and cellular energetic failure in endotoxic shock: The role of superoxide or peroxynitrite in endotoxemia". British Journal of Pharmacology. 120 (2): 259–267. doi:10.1038/sj.bjp.0700872. PMC 1564360. PMID 9117118.
  8. ^ Szabó, Csaba; Ischiropoulos, Harry; Radi, Rafael (August 2007). "Peroxynitrite: biochemistry, pathophysiology and development of therapeutics". Nature Reviews Drug Discovery. 6 (8): 662–680. doi:10.1038/nrd2222. ISSN 1474-1776. PMID 17667957. S2CID 33609069.
  9. ^ Szabó, Csaba; Mabley, Jon G.; Moeller, Suzanne M.; Shimanovich, Roman; Pacher, Pál; Virag, László; Soriano, Francisco G.; Van Duzer, John H.; Williams, William; Salzman, Andrew L.; Groves, John T. (October 2002). "Part I: pathogenetic role of peroxynitrite in the development of diabetes and diabetic vascular complications: studies with FP15, a novel potent peroxynitrite decomposition catalyst". Molecular Medicine (Cambridge, Mass.). 8 (10): 571–580. doi:10.1007/BF03402167. ISSN 1076-1551. PMC 2039946. PMID 12477967.
  10. ^ Szabó, C; Zingarelli, B; O'Connor, M; Salzman, A L (1996-03-05). "DNA strand breakage, activation of poly (ADP-ribose) synthetase, and cellular energy depletion are involved in the cytotoxicity of macrophages and smooth muscle cells exposed to peroxynitrite". Proceedings of the National Academy of Sciences. 93 (5): 1753–1758. Bibcode:1996PNAS...93.1753S. doi:10.1073/pnas.93.5.1753. ISSN 0027-8424. PMC 39853. PMID 8700830.
  11. ^ Szabó, Csaba; Virág, László; Cuzzocrea, Salvatore; Scott, Gwen S.; Hake, Paul; O’Connor, Michael P.; Zingarelli, Basilia; Salzman, Andrew; Kun, Ernest (1998-03-31). "Protection against peroxynitrite-induced fibroblast injury and arthritis development by inhibition of poly(ADP-ribose) synthase". Proceedings of the National Academy of Sciences. 95 (7): 3867–3872. Bibcode:1998PNAS...95.3867S. doi:10.1073/pnas.95.7.3867. ISSN 0027-8424. PMC 19929. PMID 9520459.
  12. ^ Garcia Soriano, Francisco; Virág, László; Jagtap, Prakash; Szabó, Éva; Mabley, Jon G.; Liaudet, Lucas; Marton, Anita; Hoyt, Dale G.; Murthy, Kanneganti G. K.; Salzman, Andrew L.; Southan, Garry J. (January 2001). "Diabetic endothelial dysfunction: the role of poly(ADP-ribose) polymerase activation". Nature Medicine. 7 (1): 108–113. doi:10.1038/83241. ISSN 1078-8956. PMID 11135624. S2CID 2756443.
  13. ^ Berger, Nathan A; Besson, Valerie C; Boulares, A Hamid; Bürkle, Alexander; Chiarugi, Alberto; Clark, Robert S; Curtin, Nicola J; Cuzzocrea, Salvatore; Dawson, Ted M; Dawson, Valina L; Haskó, György (January 2018). "Opportunities for the repurposing of PARP inhibitors for the therapy of non-oncological diseases: PARP inhibitors for repurposing". British Journal of Pharmacology. 175 (2): 192–222. doi:10.1111/bph.13748. PMC 5758399. PMID 28213892.
  14. ^ Szabó, Csaba (November 2007). "Hydrogen sulphide and its therapeutic potential". Nature Reviews Drug Discovery. 6 (11): 917–935. doi:10.1038/nrd2425. ISSN 1474-1776. PMID 17948022. S2CID 17021839.
  15. ^ Papapetropoulos, Andreas; Pyriochou, Anastasia; Altaany, Zaid; Yang, Guangdong; Marazioti, Antonia; Zhou, Zongmin; Jeschke, Mark G.; Branski, Ludwik K.; Herndon, David N.; Wang, Rui; Szabó, Csaba (2009-12-22). "Hydrogen sulfide is an endogenous stimulator of angiogenesis". Proceedings of the National Academy of Sciences. 106 (51): 21972–21977. Bibcode:2009PNAS..10621972P. doi:10.1073/pnas.0908047106. ISSN 0027-8424. PMC 2799889. PMID 19955410.
  16. ^ Suzuki, Kunihiro; Olah, Gabor; Modis, Katalin; Coletta, Ciro; Kulp, Gabriella; Gerö, Domokos; Szoleczky, Petra; Chang, Tuanjie; Zhou, Zongmin; Wu, Lingyun; Wang, Rui (2011-08-16). "Hydrogen sulfide replacement therapy protects the vascular endothelium in hyperglycemia by preserving mitochondrial function". Proceedings of the National Academy of Sciences. 108 (33): 13829–13834. Bibcode:2011PNAS..10813829S. doi:10.1073/pnas.1105121108. ISSN 0027-8424. PMC 3158211. PMID 21808008.
  17. ^ Szabo, Csaba (2021-01-22). "Hydrogen Sulfide, an Endogenous Stimulator of Mitochondrial Function in Cancer Cells". Cells. 10 (2): 220. doi:10.3390/cells10020220. ISSN 2073-4409. PMC 7911547. PMID 33499368.
  18. ^ Szabo, Csaba; Coletta, Ciro; Chao, Celia; Módis, Katalin; Szczesny, Bartosz; Papapetropoulos, Andreas; Hellmich, Mark R. (2013-07-23). "Tumor-derived hydrogen sulfide, produced by cystathionine-β-synthase, stimulates bioenergetics, cell proliferation, and angiogenesis in colon cancer". Proceedings of the National Academy of Sciences. 110 (30): 12474–12479. Bibcode:2013PNAS..11012474S. doi:10.1073/pnas.1306241110. ISSN 0027-8424. PMC 3725060. PMID 23836652.
  19. ^ Szabo, Csaba (March 2016). "Gasotransmitters in cancer: from pathophysiology to experimental therapy". Nature Reviews Drug Discovery. 15 (3): 185–203. doi:10.1038/nrd.2015.1. ISSN 1474-1776. PMC 5319818. PMID 26678620.
  20. ^ Toliver-Kinsky, Tracy; Cui, Weihua; Törö, Gabor; Lee, Seung-Jin; Shatalin, Konstantin; Nudler, Evgeny; Szabo, Csaba (January 2019). Freitag, Nancy E. (ed.). "H 2 S, a Bacterial Defense Mechanism against the Host Immune Response". Infection and Immunity. 87 (1): e00272–18. doi:10.1128/IAI.00272-18. ISSN 0019-9567. PMC 6300618. PMID 30323021.
  21. ^ "CBS, H2S and Down Syndrome: new results and new perspectives". Fondation Lejeune Research (in French). 2022-02-22. Retrieved 2022-05-24.
  22. ^ Panagaki, Theodora; Randi, Elisa B.; Augsburger, Fiona; Szabo, Csaba (2019-09-17). "Overproduction of H 2 S, generated by CBS, inhibits mitochondrial Complex IV and suppresses oxidative phosphorylation in Down syndrome". Proceedings of the National Academy of Sciences. 116 (38): 18769–18771. Bibcode:2019PNAS..11618769P. doi:10.1073/pnas.1911895116. ISSN 0027-8424. PMC 6754544. PMID 31481613.
  23. ^ Panagaki, Theodora; Lozano-Montes, Laura; Janickova, Lucia; Zuhra, Karim; Szabo, Marcell P.; Majtan, Tomas; Rainer, Gregor; Maréchal, Damien; Herault, Yann; Szabo, Csaba (May 2022). "Overproduction of hydrogen sulfide, generated by cystathionine β-synthase, disrupts brain wave patterns and contributes to neurobehavioral dysfunction in a rat model of down syndrome". Redox Biology. 51: 102233. doi:10.1016/j.redox.2022.102233. PMC 9039679. PMID 35042677.
  24. ^ "History". Salzman. Retrieved 2022-05-24.
  25. ^ Jagtap, Prakash; Soriano, Francisco Garcia; Virág, László; Liaudet, Lucas; Mabley, Jon; Szabó, Éva; Haskó, György; Marton, Anita; Lorigados, Clara Batista; Gallyas, Ferenc Jr; Sümegi, Balázs (May 2002). "Novel phenanthridinone inhibitors of poly(adenosine 5′-diphosphate-ribose) synthetase: Potent cytoprotective and antishock agents*". Critical Care Medicine. 30 (5): 1071–1082. doi:10.1097/00003246-200205000-00019. ISSN 0090-3493. PMID 12006805. S2CID 41486565.
  26. ^ Writer, GEN Staff (2006-07-26). "Genentech and Inotek to Develop PARP Inhibitors for Cancer". GEN - Genetic Engineering and Biotechnology News. Retrieved 2022-05-24.
  27. ^ Randi, Elisa B.; Zuhra, Karim; Pecze, Laszlo; Panagaki, Theodora; Szabo, Csaba (2021-05-18). "Physiological concentrations of cyanide stimulate mitochondrial Complex IV and enhance cellular bioenergetics". Proceedings of the National Academy of Sciences. 118 (20): e2026245118. Bibcode:2021PNAS..11826245R. doi:10.1073/pnas.2026245118. ISSN 0027-8424. PMC 8157914. PMID 33972444.
  28. ^ Zuhra, Karim; Szabo, Csaba (May 2022). "The two faces of cyanide: an environmental toxin and a potential novel mammalian gasotransmitter". The FEBS Journal. 289 (9): 2481–2515. doi:10.1111/febs.16135. ISSN 1742-464X. PMC 9291117. PMID 34297873.
  29. ^ "Gábor Dénes Klub/doku.php/prize:dr._szabo_csaba". gabordenesklub.hu. Retrieved 2022-05-24.
  30. ^ "Kitüntetések az egészségügyben". Medical Online. Retrieved 2022-05-24.
  31. ^ "Csaba Szabo - AD Scientific Index 2022". www.adscientificindex.com. Retrieved 2022-05-24.
  32. ^ "Google Scholar Citations". accounts.google.com. Retrieved 2022-05-24.
  33. ^ Szabo, Csaba, ed. (2000-06-22). Cell Death: The Role of PARP. Boca Raton: CRC Press. doi:10.1201/9781420038897. ISBN 978-0-429-12381-8.
  34. ^ Hasko, Gyorgy; Cronstein, Bruce N.; Szabo, Csaba, eds. (2006-07-20). Adenosine Receptors: Therapeutic Aspects for Inflammatory and Immune Diseases. Boca Raton: CRC Press. doi:10.1201/9781420005776. ISBN 978-0-429-12647-5.
  35. ^ "Biomolecules". www.mdpi.com. Retrieved 2022-05-24.

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