Igor Stagljar Professor

Diploma, University of Zagreb, Croatia, 1990
Ph.D., Swiss Federal Institute of Technology (ETH), Zurich, Switzerland 1994
PDF, University of Zurich, Switzerland 1995-2000
Visiting Fellow, University of Washington, Seattle, USA 2001

Donnelly Centre for Cellular and Biomolecular Research Room 1204

Protein Interaction Networks regulating Cell Signaling and Membrane Transport in Health and Disease
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Research Synopsis

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) technology, a powerful tool 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 has lead to many groundbreaking discoveries, including the elucidation of functions of various integral membrane proteins involved in human health and disease.

Figure 1.
An interactome of the human Epidermal Growth Factor Receptor (EGFR) mapped by MYTH as adapted from Deribe, L.Y. et al. (2009)

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 .


Selected Publications

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.

Thaminy, S., Auerbach, D., Arnoldo, A., and Stagljar, I. (2003) Identification of novel ErbB3-interacting proteins using the split-ubiquitin membrane yeast two-hybrid technology, Genome Res 13, 1744-1753.

Miller, J., Lo, R., Desmarais, C., Stagljar, I., Noble, W., and Fields, S. (2005) An interaction network of yeast integral membrane proteins, Proc Natl Acad Sci USA 102, 12123-12128.

Jovanovic, S., Du, Q., Crawford, R.M., Budas, G.R., Stagljar, I., Jovanovic, A. (2005) GAPDH serves as an accessory protein of the cardiac sarcolemmal KATP channel. EMBO Rep 6, 848-852.

Suter, B., Fetchko, M.J. Imhof, R., Graham, C., Stoffel-Studer, I., Zbinden, C., Raghavan, M., Benetti, L., Hort, J., Filingham, J., Greenblatt, J.F., Guri N. Giaever, G.N., Nislow, C., and Stagljar, I. (2007) Examining protein-protein interactions using endogenously tagged yeast arrays: the Cross-and-Capture system, Genome Res 17, 1774-1782.

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 ( i MYTH) Analysis, Mol Cell 26, 15-25.

Gisler, S.M., Kittanakom, S., Fuster, D., Radanovic, T., Wong, V., Bertic, M., Hall, R.A., Engels, K., Murer, H., Biber, J., Markovic, D., Moe, O.W., and Stagljar, I (2008) Monitoring protein-protein interactions between the mammalian integral membrane transporters and PDZ-interacting partners using a modified split-ubiquitin membrane yeast two-hybrid system , Mol Cell Proteomics 7, 1362-1377.

Arnoldo, A., Curak, J., Kittanakom, S., Chevelev, I., Lee, V.T., Sahebol-Amri, M,, Koscik, B., Ljuma, L., Roy, P.J., Bedalov, A., Giaever, G., Nislow, C., A. Merrill, R., Lory, S., and Stagljar, I. (2008) Isolating small molecule inhibitors of Pseudomonas aeruginosa ExoS toxin using a yeast phenotypic screen, PLoS Genet 4, e1000005.

Deribe, Y .L ., Schmidt, M., Chandrashaker, A., Curak, J., Milutinovic, N., Buerke, L., Fetchko, M.J., Schmidt, P., Kittanakom, S., Brown, K., Jurisica, I., Blagoev, B., Zerial, M., Stagljar, I.*, and Dikic, I. *(2009) Regulation of EGF receptor endocytosis by histone deacetylase HDAC6, Sci Signal 2, ra84 (* co-corresponding authors).

Snider J., Kittanakom S., Damjanovic D., Curak J., Wong V., and Stagljar I. (2010) Detecting interactions with membrane proteins using a mem brane two-hybrid assay in yeast, Nat Protoc 5, 1281-1293.

Usenovic, M., Knight, A. L., Raj, A., Wong, V., Brown, K. R., Caldwell, G. A., Caldwell,K. A., Stagljar, I., Krainc, D. (2012) Identification of novel ATP13A2 interactors and their role in a-synuclein misfolding and toxicity, Hum Mol Genet 21, 3785-3794.

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 (* co-corresponding authors).

Mak, A.B., Stewart, J.M., Kittanakom, S., Chen, G.I., Curak, J., Gingras, A-C., Mazitschek, R., Neel, B.G., Stagljar, I., and Moffat, J. (2012) Association of CD133, HDAC6 and b-catenin promotes transcription of TCF/LEF target genes and suppresses differentiation in cancer cells, Cell Rep 2 (4), 951-63.
doi: 10.1016/j.celrep.2012.09.016

Click here for the publications list on PubMed.


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