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Igor Stagljar

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Igor Stagljar
Born1966 (age 57–58)
Zagreb
NationalityCroatian, Canadian
Alma materFaculty of Science, University of Zagreb
PartnerDarija Jašić
Scientific career
FieldsMolecular biology
InstitutionsUniversity of Toronto

Igor Stagljar is a Croatian-born Canadian molecular biologist[1] and an expert in the field of proteomics, cancer cell signalling and COVID-19 serological testing. He is a professor of Molecular Genetics and Biochemistry at Donnelly Centre at the Medical School of the University of Toronto,[2] and is also a Co-Director and Laboratory Head at the Mediterranean Institute of Life Sciences in Split (Croatia).[3] He received a BSc. (1990) from the University of Zagreb (Croatia), and a Ph.D. (1995) in molecular biology from ETH Zurich (Switzerland).

In 2018, Stagljar announced that his lab had discovered a potential treatment for a subform of non-small cell lung cancer called lung adenocarcinoma, which is caused by a triple mutation in the EGFR gene. They found that two previously described kinase inhibitors, midostaurin and gilteritinib, inhibit the EGFR triple mutant, which was resistant to all known tyrosine kinase inhibitors, including osimertinib, the latest generation of TKIs, at that time. This discovery was published two years later in Nature Chemical Biology and elicited a lot of interest in the field of molecular oncology [4] since it was the first time that scientists found that two FDA-approved drugs, midostaurin and gilteritinib, could be used to treat lung adenocarcinoma caused by the EGFR triple mutant. These two small molecule inhibitors are currently being tested in clinical settings to evaluate their efficacy and safety in treating patients with this resistant form of lung cancer.

Stagljar is known for the development and application of numerous techniques in the field of biomedical research, in order to understand how proteins interact with each other to produce either healthy or diseased cell states.[5] Over the years, his lab has made significant contributions in the development and application of interaction proteomics methods such as the split-ubiquitin Membrane Yeast Two-Hybrid (MYTH)[6] Mammalian Membrane Two-Hybrid (MaMTH),[7] Mammalian Membrane Two-Hybrid Drug Screening (MaMTH-DS),[8] and Split Intein Mediated Protein Ligation (SIMPL)[9] technologies. This has led to many ground breaking discoveries and the elucidation of functions of various proteins involved in human health and disease.[10][11][12][4][13][14][15][16] In addition, his lab is developing a novel and proprietary serological test which will help detect, manage and reduce transmission of COVID-19. During COVID-19 pandemic Stagljar and colleagues recently developed a sensitive and innovative pinprick COVID-19 serological test named SATiN (for (Serological Assay based on split TrIpart Nanoluciferase) that accurately measures in under one hour concentration of coronavirus antibodies in blood of people either infected with SARS-CoV-2 or synthesized in their bodies post vaccination.[17] SATiN is the first COVID-19 serology test that uses highly sensitive protein complementation chemistry which takes advantage of a modified form of luciferase – an enzyme that gives fireflies their light-emitting power through a biochemical reaction.[18][19][20][21][22][1] Furthermore, in collaboration with Shawn Owen’s lab at the University of Utah, Stagljar and colleagues further modified SATiN and developed Neu-SATiN method that can be used to detect the presence and potency of neutralizing antibodies against SARS-CoV-2, including the wild-type and all major variants of concern[23][24][25][26][27] Stagljar is a recipient of several prestigious national and international distinctions for his outstanding contributions to biomedicine including the Croatian Biological Society Plaque “Zdravko Lorkovic”, the highest accolade given by the Croatian Biological Society. In 2015, the University of Toronto honoured Igor Stagljar with "Inventor of the Year” award for his contribution to Canada's innovation agenda and the advancement of knowledge. [28]

In 2022, Stagljar has been elected a member of the European Molecular Biology Organization (EMBO) as well as a fellow of the Royal Society of Canada, the highest honor that Canadian individuals can achieve in the Arts and Humanities, Social Sciences and Biomedicine[29][30][31][32]

Stagljar is a co-founder of Dualsystems Biotech Inc (Schlieren, Switzerland;[33]) and Perturba Therapeutics (Toronto, Canada).[34])

References

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  1. ^ a b "Croatian-born molecular biologist works hard and plays hard in Canada".
  2. ^ "Donnelly Centre for Cellular and Biomolecular Research".
  3. ^ "MedILS > Research > Groups > Cancer Signalling & Therapeutics".
  4. ^ a b Snider, J., Hanif, A., Lee, M.E., Jin, K., Yu, A.R., Chuk, M., Damjanovic, D., Graham, C., Wierzbicka, M., Tang, P., Balderes, D., Wong, V., San Luis, B-J., Shevelev, I., Sturley, S.L., Boone, C., Babu, M., Zhang, Z., Paumi, C.M., Park, H-O., Michaelis, S., and Stagljar, I. (2013) A global analysis of the Saccharomyces cerevisiae ABC transporter interaction network: towards a greater understanding of membrane transport, Nature Chemical Biology 9, 565-572.
  5. ^ "Igor Štagljar: Scientific laborer". 8 August 2018.
  6. ^ Stagljar, I., Korostensky, C., Johnsson, N. and te Heesen, S. (1998) A new genetic system based on split-ubiquitin for the analysis of interactions between membrane proteins in vivo. Proc. Natl. Acad. Sci. USA 95, 5187-5192.
  7. ^ Petschnigg, J., Groisman, B., Kotlyar, M., Taipale, M., Zheng, Y., Kurat, C.F., Sayad, A., J. Rafael Sierra, Mattiazzi Usaj, M., Snider, J., Nachman, A., Krykbaeva, I., Tsao, M-S., Moffat, J., Pawson, T., Lindquist, S., Jurisica, I. and Stagljar, I. (2014) The mammalian-membrane two-hybrid assay (MaMTH) for probing membrane-protein interactions in human cells, Nature Methods 11, 585-592.
  8. ^ Saraon, P., Snider, J., Kalaidzidis, Y., Wybenga-Groot, L., E., Weiss, K., Rai, A., Radulovich, N., Drecun, L., Vučković, N., Vučetić, A., Wong, V., Thériault, B., Nhu-An Pham, Park, J.H., Datti, A., Wang, J., Pathmanathan, S., Aboualizadeh, F., Lyakisheva, A., Yao, Z., Wang, Y., Joseph, B., Aman, A., Moran, M.F., Prakesch, M., Poda, G., Marcellus, R., Uehling, D., Samaržija, M., Jakopović, M., Tsao, M-S., Shepherd, F.A., Sacher, A., Leighl, N., Akhmanova, A., Al-awar, R., Zerial, M., and Stagljar, I. (2020) A drug discovery platform to identify compounds that inhibit EGFR triple mutants, Nature Chemical Biology 16(5): 577-586.
  9. ^ Yao Z, Aboualizadeh F., Kroll, J., Akula, I., Snider, J., Lyakisheva, A. Tang, P., Kotlyar, M., Jurisica, I., Boxem, M., and Stagljar, I. (2020) Split Intein Mediated Protein Ligation (SIMPL), a method for detecting protein-protein interactions and their inhibition, Nature Communications 2020 May 15;11(1): 2440.
  10. ^ Paumi, C.M., Menendez, J., Arnoldo, A., Engels, K., Iyer, K., Thaminy, S., Georgiev, O., Barral, Y., Michaelis, S., and Stagljar, I. (2007) Mapping Protein-Protein Interactions for the Yeast ABC Transporter Ycf1p by Integrated Split-Ubiquitin Membrane Yeast Two-Hybrid (iMYTH) Analysis, Molecular Cell 26, 15-25.
  11. ^ Babu, M., Vlasblom, J., Pu, S., Guo, X., Graham, C., Hnatshak, O., Phanse, S., Bajaj, N., Fong, V., Chandran, S., Punna, T., Bean, B.D.M., Davey, M., Snider, J., Wong, V., Christopolous, C., Zhong, G., Li, J., Vizeacoumar, F., Stagljar, I., Conibear, E., Wodak, S.J., Emili, A., and Greenblatt, J.F. (2012) Interaction Landscape of Membrane Protein Complexes in Saccharomyces cerevisiae, Nature 489, 585-589.
  12. ^ Xie, L., Gao, S., Alcaire, S., Wang, Y., Stagljar, I., and Zhen, M. (2013) NLF-1 Regulates Neuronal Excitability through a Conserved Sodium Leak Channel, Neuron 77,1069-1082.
  13. ^ Costanzo, M., VanderSluis, B., Koch, E.N., Baryshnikova, A.,, Pons, C., Tan, G., Wang, W., Usaj, M., Hanchard, J., Lee, S.D., Pelechano, V., Styles, E.B., Billmann, M., van Leeuwen, J., van Dyk, N., Lin, Z-Y., Kuzmin, E., Nelson, J., Piotrowski, J.S., Srikumar, T., Bahr, S., Chen, Y., Deshpande, R., Kurat, C.F., Li, S.C., Li, Z., Mattiazzi Usaj, M., Okada, H., Pascoe, N., San Luis, B-J., Sharifpoor, S., Shuteriqi, E., Simpkins, S.W., Snider, J., Suresh, H.G., Tan, Y., Zhu, H., Malod-Dognin, N., Janjic, V., Przulj, N., Troyanskaya, O.G., Stagljar, I., Xia, T., Ohya, Y., Gingras, A-C., Raught, B., Boutros, M., Steinmetz, L.M., Claire L. Moore, C.L., Rosebrock, A.P., Caudy, A.A., Myers, C.L., Andrews, B.J., and Boone, C. (2016) A global genetic interaction network maps a wiring diagram of cellular function, Science, 2016 Sep 23;353 (6306).
  14. ^ Yao, Z., Darowski, K., St-Denis, N., Wong, V., Offensperger, F., Villedieu, A., Amin, S., Malty, R., Aoki, H., Guo, H., Xu, Y., Iorio, C., Kotlyar, M., Emili, A., Jurisica, I., Babu, M., Neel, B.G., Gingras, A-C., and Stagljar, I. (2017) A global analysis of the receptor tyrosine kinase - protein phosphatase interactome, Molecular Cell 65, 347-360.
  15. ^ Sokolina, K., Kittanakom, S., Snider, J., Kotlyar, M., Maurice, P., Gandía, J., Benleulmi-Chaachoua, A., Tadagaki, K., Oishi, A., Wong, V., Reyes, B.A., Brown, K.R., Kobayashi, H., Menendez, J., Auerbach, D., Angers, A., Bouvier, M., Ciruela, F., Jockers, R., Jurisica, I., and Stagljar, I. (2017) Systematic protein-protein interaction mapping for clinically-relevant human GPCRs, Molecular Systems Biology 13, 918.
  16. ^ Kennedy, S., Jarboui, M-A., Srihari, S., Raso, C., Bryan, K., Dernayka, L., Charitou, T., Bernal-Llinares, M., Herrera-Montavez, C., Krstic, A., Matallanas, D., Kotlyar, M., Jurisica, I., Curak, J., Wong, V., Stagljar, I., LeBihan, T., Imre, L., Pilla, P., Lynn, M.A., Fasterius, E., Al-Khalili Szigyarto, C., Kiel, C., Serrano, L., Rauch, N., Pilkington, R., Cammareri, P., Sansom, O., Shave, S., Auer, M., Horn, N., Klose, F., Ueffing, M., Boldt, K., Lynn, D.J., and Kolch, W. (2020) Adaptive rewiring of protein-protein interactions and signal flow in the EGFR signaling network by mutant RAS, Nature Communication 11 (1) 499, PMID 31980649.
  17. ^ Yao, Z., Drecun, L., Aboualizadeh, F., Kim, S.J., Li, Z., Wood, H., Valcourt, E.J., Manguiat, K., Plenderleith, S., Yip, L., Li, X., Zhong, Z., Yue, F.Y., Closas, T., Snider, J., Tomic, J., Drews, S.J., Drebot, M.A., McGeer, A., Ostrowski, M., Mubareka, S., Rini, J.M., Owen, S., and Stagljar, I. (2021) A homogeneous split-luciferase assay for rapid and sensitive detection of anti-SARS CoV-2 antibodies, Nature Communications 2021 Mar 22;12(1):1806. doi: 10.1038/s41467-021-22102-6.
  18. ^ Semeniuk, Ivan (22 March 2021). "'Firefly' test aims to shed light on COVID-19 vaccine endurance". The Globe and Mail.
  19. ^ "CityNews".
  20. ^ "Canadian scientists develop rapid COVID-19 antibody test using firefly enzyme | CBC.ca".
  21. ^ "Croatian Scientist Igor Štagljar and Team Developing $2 Coronavirus Antibody Test".
  22. ^ Archived at Ghostarchive and the Wayback Machine: SATiN (Serological Assay based on split Tripart Nanoluciferase). YouTube.
  23. ^ "Homogeneous surrogate virus neutralization assay to rapidly assess neutralization activity of antiSARS-CoV-2 antibodies".
  24. ^ "What COVID-19 health advice can Canadians follow for the summer surge that's upon us?". The Globe and Mail.
  25. ^ "If you got COVID early this year, you can get reinfected now, U of T study finds". Toronto Star.
  26. ^ "Old antibodies no longer effective".
  27. ^ "U of T research team develops new test to detect immunity against COVID-19 variants".
  28. ^ "Dr. Igor Stagljar Celebrated by a Prestigious Award in Native Croatia".
  29. ^ "Donnelly Centre Investigator Igor Stagljar Elected to Royal Society Of Canada And European Molecular Biology Organization".
  30. ^ "Naš uvaženi molekularni biolog: 'Postižemo globalno priznate rezultate, a u Hrvatskoj nas napadaju frustrirani pojedinci'".
  31. ^ "Jedan od naših najpriznatijih znanstvenika postao član kanadske akademije znanosti, postaje li i direktor MedILS-a nakon Miroslava Radmana? 'Ovdje imamo slobodu...'".
  32. ^ "Igor Štagljar izabran za člana kanadske akademije znanosti i umjetnosti".
  33. ^ "Dualsystems Biotech".
  34. ^ Cyclica launches Perturba Therapeutics, a spin out from the University of Toronto, creating the next-generation oncology biotech.
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