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Professor

Igor Stagljar

Molecular Genetics

PhD

Location
Terrence Donnelly Centre for Cellular & Biomolecular Research
Address
160 College Street, Room 1204, Toronto, Ontario Canada M5S 3E1
Research Interests
Cancer, Drug discovery, design, development and screening, Proteomics and proteins, Signalling, Technology development
Category
Cellular and Molecular Structure and Function, Computational and Systems Biology, Functional Genomics and Proteomics, Molecular Medicine and Human Genetics
Appointment Status
Cross-Appointed

Qualification

  • Research Fellow in Genome Sciences, University of Washington, Seattle, USA, 2001.
  • Postdoctoral Fellow in Molecular Biology, University of Zurich, Switzerland, 1995-2000.
  • PhD in Molecular Biology and Microbiology, Swiss Federal School of Technology (ETH), Zurich, Switzerland, 1995.
  • BSc in Molecular Biology, University of Zagreb, Croatia, 1990.

Courses taught

  • BCH2024H Membrane Proteomics in Biomedical Research
  • MMG1227 Special Topics in Advanced Cancer Proteomics
  • BCH444H Protein Trafficking in the Secretory and Endocytic Pathways

Cross affiliations

Department of Biochemistry, University of Toronto

Donnelly Centre

Biography

Professor Igor Stagljar’s career has been defined by a relentless pursuit of the molecular mechanisms governing cellular health and disease. He earned his PhD in Molecular Biology from ETH Zurich, where he trained under Markus Aebi and Charles Weissmann, followed by pivotal postdoctoral fellowships at the University of Zurich with Walter Schaffner and Ulrich Huebscher, focusing on the complexities of RNA transcription and DNA repair.

A transformative period as a research fellow with Stan Fields at the University of Washington—the pioneer of yeast two-hybrid technology—solidified Igor’s trajectory as a master of protein-protein interaction (PPI) technologies. After serving as an Assistant Professor at the University of Zurich (2002–2005), he joined the University of Toronto, rising to the rank of Professor in 2010. Today, his lab stands as a global leader in proteomics and a prolific innovator at the intersection of chemical genomics and drug discovery.

Awards

  • 2025, The inaugural Editor-in-Chief of the Elsevier journal Disease and Therapeutics
  • 2023, Listed among Top 50 most influential people in the Adria region by Bloomberg
  • 2022, Fellow, Royal Society of Canada
  • 2022, Member, European Molecular Biology Organization
  • 2016, Croatian Biological Society Plaque “Zdravko Lorkovic” for outstanding contributions to biology
  • 2015, The University of Toronto Innovator of the Year Award
  • 2014, Corresponding Member of the Croatian Academy of Arts and Science
  • 2014, National Award “Rudjer Boskovic” for Scientific Achievements, University of Split, Croatia
  • 2006, Leaders Technology Award, Canadian Funds for Innovation Canada

Research Overview: Disrupting the "Undruggable" Proteome

The Stagljar Lab operates at the vanguard of proteomics, specializing in the creation of high-throughput technologies that decode the complex social networks of human membrane proteins. We are widely recognized for inventing the Membrane Yeast Two-Hybrid (MYTH) and Mammalian Membrane Two-Hybrid (MaMTH) systems—technologies that have become global benchmarks for studying membrane protein interactions in their native cellular environments.

As a disruptor in the field, our lab has expanded these foundations into a robust drug-screening ecosystem (MaMTH-DS, SIMPL/SIMPL2, and CLIP-LUX). These platforms enable us to visualize and quantify protein interactions in real-time, providing a powerful lens through which to identify therapeutics for previously "undruggable" cancer targets. Since June 2025, Professor Stagljar has also steered the international scientific conversation as the inaugural Editor-in-Chief of the Elsevier journal, Disease and Therapeutics.

Current Research Frontiers

1. AI & Quantum-Driven Drug Discovery

In a landmark collaboration with Alán Aspuru-Guzik and Insilico Medicine, we are revolutionizing how medicine is found. By integrating generative AI and quantum computing with our proprietary MaMTH, SIMPL2 and CLIP-LUX platforms (as seen in Nature Biotechnology, 2025), we have built an automated pipeline to rapidly identify small molecules targeting "hard-to-drug" proteins like KRAS mutants, ubiquitin ligases, and RTKs.

2. Next-Gen Degraders

PROTACs and Molecular Glues Using our SIMPL2 and CLIP-LUX live-cell platforms, we are mapping the real-time dynamics of protein degradation. These systems are uniquely optimized for high-throughput discovery of PROTACs and molecular glues, targeting the essential protein-protein interactions that drive cancer progression.

3. Mapping the Human Cancer Membrane Proteome (HCMP)

We are currently leading an ambitious effort to map the global interactome of every major cancer-associated membrane protein. This "Human Cancer Membrane Proteome" project utilizes our MaMTH-HTS system to uncover the hidden functional pathways that fuel malignancy, providing a blueprint for the next generation of precision medicine.

4. Decoding Cystic Fibrosis (CF)

Our lab is conducting a massive exploration of the CFTR interactome. By screening over 400 Solute Carrier (SLC) transporters against wild-type and ΔF508-CFTR, we have identified "modifier" targets that regulate pH and ion balance. These findings offer a new therapeutic framework for restoring lung function in CF patients.

5. Translational Impact & Global Partnerships

Our science is built for real-world impact. Through deep-rooted collaborations with industry giants—including Genentech, Novartis, Amgen, Merck, Insilico Medicine, and Pfizer—we bridge the gap between basic biochemical discovery and the accelerated delivery of life-saving drugs.

Selected Publications

1.    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.

2.    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. doi: 10.1016/j.molcel.2016.12.004. [Featured on the journal cover of the January 19, 2017 issue].

3.    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. doi: 10.1038/s41589-020-0484-2.

4.    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. doi: 10.1038/s41467-020-16299-1.

5.    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. [Featured on CBC’s The National, CityNews TV, Global News, Toronto Star and The Globe and Mail].

6.    Sun Jin Kim+, Zhong Yao+, Morgan C. Marsh, Debra M. Eckert, Michael S. Kay, Anna Lyakisheva, Maria Pasic, Aiyush Bansal, Chaim Birnboim, Prabhat Jha, Julio C. Delgado, Marc G. Elgort, Robert A. Campbell, Elizabeth A. Middleton, Igor Stagljar*, Shawn C. Owen* (2022) Homogeneous Surrogate Virus Neutralization Assay to Rapidly Assess Neutralization Activity of Anti-SARS-CoV-2 Antibodies. Nature Communications 13(1):3716 (* co-corresponding authors); DOI 10.1038/s41467-022-31300-9. [Featured on CTV News, CityNews TV, CP 24 News, Global News, Toronto Star and The Globe and Mail].

7.    Zhong Yao, Kim, J., Geng, B., Chen, J., Lyakisheva, A., Snider, J., Rudan Dimlic, M., Raic, S., and Stagljar, I. (2025) A Split Intein and Split Luciferase-Coupled System for Detecting Protein-Protein Interactions. Molecular Systems Biology 21(2):107-125. doi: 10.1038/s44320-024-00081-2. (featured on the April 2025 cover of Molecular Systems Biology)

8.    Ghazi Vakili, M., Christoph Gorgulla, C., Kumar, A.N., Bezrukov, D., Varoli, D., Aliper, A., Polykovsky, D., Padmanabha Das, K.M., Snider, J., Lyakisheva, A., Hosseini Mansob, A., Yao, Z., Bitar, L., Radchenko, E., Ding, X., Liu, J., Meng, F., Ren, F., Cao, Y., Stagljar, I.*, Aspuru-Guzik, A*., and Zhavoronkov, A.* (2025) Quantum Computing-Enhanced Algorithm Unveils Novel Inhibitors for KRAS. Nature Biotechnology, Jan 22, 2025, doi: 10.1038/s41587-024-02526-3. (* co-corresponding authors). [Voted top 10 papers of 2025 by editors of Nature Biotechnology; Featured on CNN, Psychology Today, and the journal cover of the December 2025 issue].