Impact of targeted agents on oncosome profiles in cancer - ANAT 396 Undergraduate Research Project Application Form

Supervisor's Name: Janusz RAK

Supervisor's Email: janusz.rak [at] mcgill.ca

Supervisor's Phone: 514-412-4400 ext 22342

Supervisor's Website: na

Supervisor's department: Experimental Medicine

Course number: ANAT 396 (Anatomy and Cell Biology)

Term: Winter 2013-2014

Project start date: Monday, January 6, 2014

Project end date: Friday, April 11, 2014

Project title: Impact of targeted agents on oncosome profiles in cancer

Project description (50-100 words suggested): Cancer cells emit oncogene-containing extracellular vesicles (oncosomes), which act as biological mediators and reservoirs of molecular biomarkers reflective of malignant transformation. We hypothesize that successful obliteration of the respective oncogenic pathways with specific pharmacological inhibitors will be reflected in the emission profiles of these vesicles, including their numbers, types, and both content and state of activation (phosphorylation) of their corresponding oncoprotein targets. This notion will be tested in the A431 human epithelial cancer model system, which is driven by the oncogenic epidermal growth factor receptor (EGFR), and exquisitely responsive to EGFR inhibitors, such as CI-1033. The aims of this project is to perform nanoparticle tracking analysis of oncosomes emitted by CI-1033-treated and control A431 cells, and test them by Western blotting and ELISA assays for the content of EGFR and phospho-EGFR, as well as characteristics specific for distinct vesiculation pathways, including: Rab proteins, Alix, TSG101, HSP70 and flotilin. These experiments will illuminate the impact of prototypic anticancer targeted agents on tumor-derived vesicles that can be recovered from plasma of cancer patients and remotely reveal the effects of these drugs on oncogenic targets (liquid biopsy). This knowledge could contribute to development of novel biomarkers and companion diagnostics in cancer.

Prerequisite: 1 term completed at McGill + CGPA of 3.0 or higher; or permission of instructor.

Grading scheme (The final report must be worth at least 50% of final grade): final report 50%, lab research 50%

Other project information: The project involves in vitro culture of cancer cells and preparation of vesicles as well as cell lysates and other samples for analysis.

Project status: This project is taken.

Ethics, safety, and training: Supervisors are responsible for the ethics and safety compliance of undergraduate students. This project involves: Biohazardous substances; Handling chemicals; Using lasers.