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.[4]
Stagljar has performed biomedical research to understand how proteins interact with each other to produce either healthy or diseased cell states.[5] Over the years, his lab has studied 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.[10][11][12][4][13][14][15][16]
During COVID-19 pandemic Stagljar and colleagues developed 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 was 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] 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.[23][24][25][26][27]
Stagljar is a co-founder of Dualsystems Biotech Inc (Schlieren, Switzerland;[28]) and Perturba Therapeutics (Toronto, Canada).[29])
Awards
Croatian Biological Society Plaque “Zdravko Lorkovic” by the Croatian Biological Society[30]
"Inventor of the Year” from the University of Toronto for contributing to Canada's innovation agenda and the advancement of knowledge in 2015[citation needed]
^ abSnider, 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.
^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.
^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.
^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.
^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.
^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.
^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.
^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.
^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).
^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.
^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.
^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, PMID31980649.
^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.
