Igor Stagljar

Igor received his Ph.D. in Molecular Biology from ETH Zurich in Switzerland, where he worked in Markus Aebi’s lab studying protein glycosylation in yeast and humans. His postdoctoral fellowship was at the University of Zurich with Walter Schaffner and Ulrich Huebscher, where he studied RNA transcription and DNA repair. In addition, Igor was a visiting scientist at the University of Washington in Seattle with Stan Fields, the inventor of the yeast two-hybrid technology. Igor was Assistant Professor at the University of Zurich from 2002-2005, Associate Professor at the University of Toronto since 2005, and Professor since 2010.

The Stagljar Lab focuses on elucidating the functions of a specific class of proteins – membrane proteins – which play a wide variety of roles in the cell. The group examines how these membrane proteins interact with each other as well as proteins not necessarily bound to the cell membrane. To do this, we have developed two unique technologies: the classic Membrane Yeast Two-Hybrid (MYTH) and the newly created Mammalian Membrane Two-Hybrid (MaMTH), which enables researchers to study this clinically relevant class of proteins.

Interactome networks of integral membrane proteins and their roles in health & disease

A key focus of the Stagljar lab is to understand the function of a wide range of pharmaceutically relevant yeast and human integral membrane proteins involved in cell signaling and membrane transport at a systems level. Despite extensive research in the past decade, there is a lack of in-depth understanding of protein networks associated with these integral membrane proteins because of their unique biochemical features, enormous complexity and multiplicity. This is a major obstacle for designing improved and more targeted therapies, and importantly, understanding the biology of deregulation of these integral membrane proteins which leads to numerous human diseases.

Our lab is internationally known for the development of the split-ubiquitin Membrane Yeast Two-Hybrid (MYTH) and Mammalian Membrane Two-Hybrid (MaMTH) technologies, powerful tools for the identification of interactors of a given integral membrane protein and one of the key interactive proteomic technologies available to researchers today. To date, MYTH and MaMTH have lead to many groundbreaking discoveries, including the elucidation of functions of various integral membrane proteins involved in human health and disease.

Currently, there are several large-scale, ongoing projects in the lab aimed towards elucidating how yeast and human integral membrane proteins and their interacting partners lead to either diseased or healthy states. These studies include mapping of protein interaction networks of various families of membrane proteins such as ABC Transporters, Receptor Tyrosine Kinases, G-protein Coupled Receptors, Cancer Stem Cell Receptors and Ion Channels. Subsequently, proteins and pathways identified by our initial protein interaction screens are studied in depth using various genetic, molecular, and biochemical approaches, shedding light on cell signaling and membrane transport pathways, which control cell behavior in normal and disease cells at a systems level.

In addition, because the Stagljar group studies ‘druggable’ membrane proteins, they hope their work will unveil new avenues for diagnosis and treatment of many human diseases.

Proteomics

A key focus of our lab is to understand the function of a wide range of pharmaceutically relevant yeast and human integral membrane proteins involved in cell signaling and membrane transport at a systems level. Despite extensive research in the past decade, there is a lack of in-depth understanding of protein networks associated with these integral membrane proteins because of their unique biochemical features, enormous complexity and multiplicity. This is a major obstacle for designing improved and more targeted therapies, and importantly, understanding the biology of deregulation of these integral membrane proteins which leads to numerous human diseases.

Our lab is internationally known for the development of the split-ubiquitin Membrane Yeast Two-Hybrid (MYTH) and Mammalian Membrane Two-Hybrid (MaMTH) technologies, powerful tools for the identification of interactors of a given integral membrane protein and one of the key interactive proteomic technologies available to researchers today. To date, MYTH and MaMTH have lead to many groundbreaking discoveries, including the elucidation of functions of various integral membrane proteins involved in human health and disease.

Currently, there are several large-scale on-going projects in the lab aimed towards elucidating how yeast and human integral membrane proteins and their interacting partners lead to either diseased or healthy states. These studies include mapping of protein interaction networks of various families of membrane proteins such as ABC Transporters, Receptor Tyrosine Kinases, G-protein Coupled Receptors, Cancer Stem Cell Receptors and Ion Channels. Subsequently, proteins and pathways identified by our initial protein interaction screens are studied in depth using various genetic, molecular, and biochemical approaches, shedding light on cell signaling and membrane transport pathways, which control cell behavior in normal and disease cells at a systems level.

Cell Signaling

Our lab studies abnormal proteins on the surface of human cells (also called receptors), which are associated with non-small cell lung cancer (NSCLC) using a newly developed MaMTH technology in hopes of getting a better understanding of this widespread and deadly form of cancer. Using this new technology, we recently identified a key protein called CRK II which interacts with the oncogenic version of EGFR, and which, when synthesized in large quantities, stimulates the growth of NSCLC cells. We now study in detail the exact role of CRK II in the onset and progression of NSCLC.

By applying our newly developed MaMTH technology, we hope to identify additional proteins that interact with oncogenic version of EGFR and regulate the proliferation of NSCLC cells. In summary, our work will add greatly to the field and provide other researchers with new knowledge, and potential new drug targets, to help combat NSCLC.

Membrane Transport

ABC Binding Cassette (ABC) proteins comprise one of the largest known protein superfamilies, using the power of nucleotide binding and hydrolysis to mediate a diverse range of cellular functions. A major class of ABC proteins are the integral membrane ABC transporters, which are responsible for the movement of a wide variety of substances across cellular membranes. ABC transporters are of great clinical interest because of the key roles they play in human health and disease. Dysfunction of ABC transporters is associated with a variety of human diseases, such as cystic fibrosis, pseudoxanthoma elasticum, adrenoleukodystrophy, Zellweger syndrome, familial hyperinsulinemic hypoglycemia of infancy, Dubin-Johnson syndrome, hepatic cholestasis, the retinal syndrome Stargardt’s dystrophy, and the cholesterol transport disorder Tangier disease. ABC transporters are also associated with multidrug resistance of cancer cells and pathogenic microorganisms, and can provide a serious barrier to effective drug therapy.

In an effort to gain a better understanding of the regulation and molecular function of these proteins we recently used the MYTH system to map the complete interactome of all non-mitochondrial ABC transporters found in the yeast Saccharomyces cerevisiae. Our results revealed that ABC transporters physically associate with a functionally diverse array of proteins and show far greater integration with cellular systems than previously known. We are currently seeking to expand upon this work by using our powerful new MaMTH technology to map the interactions of the complete complement of ABC transporters found in humans.

Appointments, Cross Affiliations, Memberships

 Professor, Department of Molecular Genetics
Donnelly Centre for Cellular and Biomolecular Research
Co-founder of the biotech company Perturba Therapeutix Inc., Toronto, ON, Canada

Courses Taught

BCH473Y Advanced Research Project in Biochemistry
BCH426H (BCH1426H) Regulation of Signalling Pathways
BCH444H Protein Trafficking in the Secretory and Endocytic Pathways
BCH2106H Membrane Proteomics in Biomedical Research
MMG1313H Membrane Proteomics in Biomedical Research MMG1313H

Awards and Distinctions

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 the Scientific Achievements, University of Split, Croatia  
2006 — Leaders Technology Award, Canadian Funds for Innovation Canada