|R e s e a r c h I n t e r e s t s|
Work in the Nabi lab focuses on the cell biology of cancer and the use of super-resolution microscopy to study cellular domains.
1) The role of non-caveolar scaffold domains and the galectin lattice in cancer cell migration and focal adhesion tension.
We study the role of plasma membrane domain effectors galectin-3 and caveolin-1 in focal adhesion dynamics and tension in metastatic cancer cells. We have developed network analysis of dSTORM super resolution microscopy to define the molecular architecture of caveolae and scaffolds and are now studying the structural changes in these membrane domains associated with tumor cell migration and mechanical stress. Our characterization of the proteome and transcriptome of tumor cell pseudopodia has identified multiple pseudopod-localized effectors whose role in pseudopod-specific actin dynamics and focal adhesion tension is being studied.
2) The role of the cancer-associated ubiquitin ligase Gp78 in the regulation of endoplasmic reticulum-mitochondria contacts and mitophagy.
We have defined the role of Gp78 (also known as autocrine motility factor receptor (AMFR)), a cancer-associated receptor and E3 ubiquitin ligase in endoplasmic reticulum (ER) associated degradation, in ER-mitochondria interaction and mitophagy. We have shown that Gp78 and its ligand AMF control rough ER-mitochondria contacts and are defining the underlying molecular mechanisms and applying STED super-resolution microscopy to define the organization of the ER and its interaction with mitochondria.
|S e l e c t e d P u b l i c a t i o n s|
Further publications can be found here.
|I m a g e s|
|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 mCD 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).|
|After mitochondrial depolarization with carbonyl cyanide m-chlorophenylhydrazone (CCCP), of Cos7 cells transfected with Flag-tagged Gp78 ubiquitin ligase (red), the autophagosome-associated protein LC3-GFP (green) is recruited to the Gp78 labeled ER that is closely associated with mitochondria (blue). Colocalization between LC3-GFP and the Gp78 labeled ER (yellow) is indicative of a role for the ER in Gp78-dependent mitophagy. Fu et al, Mol Biol Cell, in press. (Image by Peter T. C. Wang, University of British Columbia)|