CellPhys Faculty

BSc Biochemistry (McGill University)
PhD Cancer Metastasis (Weizmann Institute of Science)

Office: 604-822-7000, Lab: 604-822-7329
Email: irnabi@interchange.ubc.ca

Research Interests

Work in the Nabi lab focuses on cell biology and its relation to disease, in particular cancer. The expression of cellular domains, ranging from cell polarity to organelle biogenesis to membrane microdomain organization, plays an important role in regulating cell function. Domain localization is critical to the regulation of receptor activation and our work has elaborated on the functional significance of various cellular domains in receptor function in cell motility.

Specific projects include:
• The role of autocrine motility factor receptor (AMFR, also gp78), a cancer-associated receptor and E3 ubiquitin ligase in endoplasmic reticulum associated degradation (ERAD) and ER-mitochondria interaction.
• Development of novel anti-cancer therapeutics based on the raft-dependent endocytosis of autocrine motility factor (AMF), the gp78/AMFR ligand.
• The role of plasma membrane domains and their effectors, including galectin-3 and caveolin-1, in receptor signaling and focal adhesion dynamics in metastatic cancer cells.
• Characterization of the proteome and transcriptome of tumor cell pseudopodia and the regulation of tumor cell migration and metastasis.

Selected Publications

Bharat Joshi and Ivan R. Nabi (2010). A role for KAI1 in promotion of cell proliferation and mammary gland hyperplasia by the Gp78 ubiquitin ligase. J. Biol. Chem. (Epub before print – Jan 20, 2010).

James W. Dennis, Michael Demetriou and Ivan R. Nabi (2009). Metabolism, cell surface organization and disease. Cell 139, 1229-41.

James W. Dennis, Ken S. Lau, Michael Demetriou and Ivan R. Nabi (2009). Adaptive regulation at the cell surface by N-glycosylation. Traffic 10, 1569-78.

Aruna D. Balgi, Bruno D. Fonseca, Elizabeth Donohue, Trevor C. F. Tsang, Patrick Lajoie, Christopher G. Proud, Ivan R. Nabi and Michel Roberge (2009). Screen for Chemical Modulators of Autophagy Reveals Novel Therapeutic Inhibitors of mTORC1 Signaling. PLOS One 4, e7124.

Maria Fairbank, Pascal St-Pierre, Ivan R. Nabi. (2009). The complex biology of autocrine motility factor/phosphoglucose isomerase (AMF/PGI) and its receptor, the gp78/AMFR E3 ubiquitin ligase. Mol. Biosyst. 5, 793-801.

Ivan R. Nabi (2009). Cavin fever: Regulating caveolae. Nature Cell Biology 11, 793-801.

Jacky G. Goetz*, Patrick Lajoie*, James W. Dennis, Ivan R. Nabi (2009). Lattices, rafts and scaffolds: Domain regulation of receptor signaling at the plasma membrane. J. Cell Biol. 185(3):381-5. *equal contribution

P Lajoie, LD Kojic, S Nim, L Li, JW Dennis, IR Nabi (2009). Caveolin-1 regulation of the raft-dependent endocytosis of cholera toxin b. J Cell Molec Med Epub (Mar 6 2009).

Liliana D. Kojic, Sam M. Wiseman, Fariba Ghaidi, Bharat Joshi, Hinyu Nedev, H. Uri Saragovi, Ivan R. Nabi (2008). Raft-dependent endocytosis of autocrine motility factor/phosphoglucose isomerase: a potential drug delivery route for tumor cells. PLoS ONE 3(10):e3597.

Heather C. Stuart, Zongjian Jia, Anat Messenberg, Bharat Joshi, T. Michael Underhill, Hakima Moukhles, Ivan R. Nabi (2008). Localized Rho activation regulates RNA dynamics and compartmentalization in tumor cell protrusions. J. Biol Chem 283, 34785-95.

Bharat Joshi, Scott Strugnell, Jacky G. Goetz, Liliana D. Kojic, Michael E. Cox, Obi L. Griffith, Steven J. Jones, Sher-Ping Leung, Hamid Masoudi, Samuel Leung, Sam M. Wiseman and Ivan R. Nabi (2008). Phospho-caveolin-1 regulates Rho/ROCK-dependent focal adhesion dynamics and tumor cell migration. Cancer Research. 68(20):8210-20.

Jacky G. Goetz*, Patrick Lajoie*, Sam M. Wiseman, Ivan R. Nabi. (2008). Caveolin-1 in tumor progression: the good, the bad and the ugly. Cancer Metastasis Rev. 2008 May 28. [Epub ahead of print].

Sam M. Wiseman, Obi L. Griffith, A. Melck, Hamid Masoudi, Alan Gown, Ivan R. Nabi, Steven J. Jones. (2008). Evaluation of type 1 growth factor receptor family expression in benign and malignant thyroid lesions. Am J Surg. 195, 667-73.

Jacky G. Goetz, Bharat Joshi, Patrick Lajoie, Scott S. Strugnell, Trevor Scudamore, Liliana D. Kojic, Ivan R. Nabi (2008). Concerted regulation of focal adhesion dynamics by galectin-3 and tyrosine phosphorylated caveolin-1. J. Cell Biol. 180, 1261-1275. (highlighted in Nature’s Functional Glycomics Gateway, Faculty of 1000).

Connie G. Chiu, Pascal St. Pierre, Ivan R. Nabi, and Sam M. Wiseman (2008). Autocrine motility factor receptor : a clinical review. Expert Rev. Anticancer Therapy 8, 207-217.

Patrick Lajoie, Emily Partridge, Ginette Guay, Jacky G. Goetz, Judy Pawling, Annick Lagana, Bharat Joshi, James W. Dennis and Ivan R. Nabi (2007). Plasma membrane domain organization regulates EGFR signaling in tumor cells. J. Cell Biol. 179, 341-356 (selected for cover image and highlighted in JCB’s In this issue, Nature’s Functional Glycomics Gateway and Faculty of 1000).

Jacky G. Goetz*, Hélène Genty*, Pascal St-Pierre*, Thao Dang,Remy Sauvé, Wayne Vogl, And Ivan R. Nabi (2007). Reversible interactions between smooth endoplasmic reticulum domains and mitochondria are regulated by physiological cytosolic calcium levels. J. Cell Sci. 120, 3553-3564 (Selected For Cover Image) *equal contribution.

Liliana D. Kojic, Bharat Joshi, Patrick Lajoie, Phuong U. Le, Michael Cox, Dmitry Turbin, Sam Wiseman and Ivan R. Nabi (2007). Phosphoinositide-3-kinase-, raft-dependent endocytosis of autocrine motility factor selectively targets p-Akt-positive, caveolin-1-negative breast carcinoma cells. J. Biol. Chem. 282, 29305-29313.

Patrick Lajoie and Ivan R. Nabi (2007). Regulation of raft-dependent endocytosis. J. Cell Molec. Med. 11, 644-653.

Annick Lagana*, Jacky G. Goetz*, Pam Cheung, Avraham Raz, James W. Dennis, and Ivan R. Nabi (2006). Mgat5-modified N-glycans and galectin-3 regulate tumor cell remodeling of the fibronectin matrix. Mol. Cell. Biol. 26, 3181-93 (selected for cover image Nov, 2006).

Images

Plasma membrane domain organization regulates EGFR signaling in tumor cells. Cover image, Journal of Cell Biology 179, 2007.

Expression of mutant dynK44A induces caveolae in ras-transformed NIH-3T3 cells. Ras-transformed NIH-3T3 cells exhibit few caveolae (top) but following adenoviral infection with mutant dynamin (K44A), plasma membrane profiles show the dramatically increased expression of smooth caveolar invaginations (middle). DynK44A-infected cells pretreated with 5 mM m

CD exhibit no caveolar invaginations (bottom). Glycolipid rafts can therefore invaginate to form caveolae independently of caveolin expression. Le et al. J. Biol. Chem. 277, 3371-3379 (cover image).

The 3F3A anti-AMFR mAb recognizes a subset of expressed AMFR localized to a subdomain of the ER. In MDCK cells, transfected AMFR-GFP colocalizes with the endoplasmic reticulum marker calnexin (CN), but the 3F3A anti-AMFR antibody selectively recognizes a distinct subdomain of the endoplasmic reticulum (ER). A conformationally distinct form of AMFr is therefore associated with a smooth subdomain of the ER that is distinct from the ER labeled with antibodies to calnexin (CN).