Title:
Professor 

Institute:
University of British Columbia, Vancouver

Department:  
Cellular & Physiological Sciences

Province:
British Columbia

Training:   
Postdoctoral Fellow, Medical Research Council of Canada
Postdoctoral Fellow, Cornell University Medical College, New York, NY, USA
Postdoctoral Fellow, Michigan Cancer Foundation, Detroit, MI, USA
PhD, Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel 
BSc Honors, Department of Biochemistry, McGill University, Montreal, Quebec

Research interests:
Cell biology and its relation to disease, in particular cancer 

Recognitions:  
Researcher of the Year Award, Dept. of Cellular and Physiological Sciences, University of British Columbia
Investigator, Canadian Institutes for Health Research
Chercheur-boursier Senior, Fonds de la recherche en santé du Québec

Career highlights:
Dr. Nabi has been a committee member in research organisms, such as CIHR, CRS, NCIC, AHFMR, FRSQ-FCAR Santé, and MRC. He is also on the editorial boards of the American Journal of Pathology and the Journal of Epithelial Biology and Pharmacology.

Research Projects

Project title:
Autocrine motility factor as a targeted delivery agent for breast cancer treatment

Funding period: 
2010-2012

Program:
Operating Grant (basic research)

Summary:
We have developed a novel targeted therapeutic for breast cancer, called AMF/PGI-paclitaxel. When AMF/PGI binds to its receptor (gp78/AMFR) it is efficiently and selectively taken up by cancer cells. By linking AMF/PGI to paclitaxel (an anti-cancer drug used clinically for breast cancer treatment) we expect to deliver this chemotherapeutic drug more selectively to breast cancer cells, but not normal body cells. This should increase the efficacy and reduce toxic side effects of breast cancer treatment with paclitaxel.  We will assess whether AMF/PGI-paclitaxel prevents tumor growth, induces tumor regression and prolongs survival in mice bearing human breast tumors. We will also study gp78/AMFR expression and AMF/PGI uptake in freshly isolated human breast cancers. If successful, these studies will suggest that AMF/PGI-paclitaxel is an anti-cancer drug of potential value for treatment of human breast cancer and lead to its development for clinical application.

***

Project title:
Molecular Characterization of the Pseudopodia of Metastatic Tumor Cells

Funding period:  
2011-2013

Program:
Operating Grant (Basic Research)

Summary:
The most devastating aspect of cancer is the ability of tumor cells to migrate to other sites and establish new colonies or metastases. We have characterized the molecules, both RNA and protein, that are found in the pseudopodia and that are critical to the ability of tumor cells to migrate. Certain of these were found to be required to change the phenotype of metastatic cancer cells from an epithelial phenotype (in which cells are closely attached one to the other) to a mesenchymal phenotype (in which cells separate from and migrate away from one another). The importance of the identified pseudopod proteins to promote what is called epithelial to mesenchymal transition suggests that they may be possible targets for anti-metastasis therapy. In this grant, we will determine how these molecules regulate pseudopod formation and cancer cell migration. We will also identify molecular regulators (microRNA) that inhibit pseudopod formation that may lead to the development of novel cancer therapeutics.

CRS publications:

Jay Shankar, Anat Messenberg, Jacky Chan, T. Michael Underhill, Leonard Foster and Ivan R. Nabi (2010). Pseudopodial Actin Dynamics Control Epithelial-Mesenchymal Transition in Metastatic Cancer Cells. Cancer Research (In press).

Jay Shankar and Ivan R. Nabi (2010). Characterization of mRNA in isolated pseudopodia. In Messages on the move: Techniques in RNA Visualization (Methods in Molecular Biology Book Series, Humana Press). Editor J. Gerst (In press).

Heather C. Stuart, Zongjian Jia, Anat Messenberg, Bharat Joshi, T. Michael Underhill, Hakima Moukhles, Ivan R. Nabi (2008) Localized Rho GTPase Activation Regulates RNA Dynamics and Compartmentalization in Tumor Cell Protrusions. J. Biol. Chem. 283, 34785

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). Phosphorylated caveolin-1 regulates Rho/ROCK-dependent focal adhesion dynamics and tumor cell migration and invasion. Cancer Res. 68(20):8210-20.

Zongjian Jia, Julie Vadnais, Michael Lu, Josette Noël and Ivan R. Nabi (2006). Rho/ROCK-dependent pseudopodial protrusion and cellular blebbing are regulated by p38 MAP kinase in tumor cells exhibiting autocrine c-Met activation. Biol. Cell 98, 337-51

Zongjian Jia, Laurence Barbier, Heather Stuart, Mohammad Amraei, Steven Pelech, James W. Dennis, Pavel Metalnikov, Paul O'Donnell and Ivan R. Nabi (2005). Tumor cell pseudopodial protrusions: localized signaling domains coordinating cytoskeleton remodelling, cell adhesion, glycolysis, RNA translocation and protein translation. J. Biol. Chem. 280, 30564-73.

Past CRS projects:

2010 Autocrine motility factor as a targeted delivery agent for breast cancer treatment

2009 Molecular Characterization of the Pseudopodia of Metastatic Tumour Cells

2006 Molecular Characterization of the Pseudopodial Domains of Metastic tumor Cells

2003 Molecular characterization of tumor cell pseudopodia

1994 The role of niacin status and poly(ADP-ribose) metabolism in nitrosourea-induced carcinogenesis