Defining the expression of PRLs family members and their modulation in the immune cells of the tumor stroma - MIMM 397 Undergraduate Research Project Application Form

Supervisor's Name: Dr. Michel L. Tremblay

Supervisor's Email: michel.tremblay [at] mcgill.ca

Supervisor's Phone: 514-398-7290

Supervisor's Website: http://www.medicine.mcgill.ca/cancercentre/tremblaylab/

Supervisor's department: Biochemistry

Course number: MIMM 397 (Immunology)

Term: Winter 2014-2015

Project start date: Friday, September 4, 2015

Project end date: Monday, December 7, 2015

Project title: Defining the expression of PRLs family members and their modulation in the immune cells of the tumor stroma

Project description (50-100 words suggested): Cellular signaling networks operate on a tightly regulated system of protein phosphorylation and dephosphorylation. With 109 members in humans, the protein tyrosine phosphatase protein superfamily acts on many of these pathways to maintain the balance of pathway activation and deactivation within the cell. The majority of these proteins are expressed in the immune system, therefore it is no surprise that most common genetic disease associations of these are of immune origin. The phosphatase of regenerating liver (PRL) proteins represent a group of protein tyrosine phosphatases that has been implicated in a number of diseases, and largely studied in the context of cancer metastasis.
However, little is known about their physiological function. One such member, PRL-2, was recently found to be involved in maintaining magnesium homeostasis within the cell, and being associated with the most metastatic cancers. In a previous study, I have characterized the expression pattern of the PRL-2 enzymes in mouse tissues based on a BetaGeo gene insertion vector (Gungabeesoon et al. In preparation). Characterization of the PRL-2 heterozygous BetaGeo mice indicates that this phosphatase is expressed in many tissues including several cells of the immune system. Hence we would like to propose that this expression pattern may be crucial for the development and exit of tumor cells from the initial tumor site. Indeed, PRL’s may be further active in the stromal cells and even those that are repressing the immune response to tumor. Using C57Bl6 syngeneic EB7 lymphoma tumor cells, I will examine the heterogeneity profile of stromal cells for the expression of PRL-2 BetaGeo using either a heterozygous mouse (with no obvious phenotype) and with a knockout homozygous host (presenting several physiological defect). Defining the physiological role of PRL-2 in the tumor stroma would not only provide a greater understanding of the processes that govern magnesium dependent cell activity but also contribute insight into potential pathological roles of this phosphatase in the tumor growth.

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 grade shall be based on laboratory performance as evaluated by the research supervisor (50%) and the final written research report (minimum 10 pages) graded by the supervisor and the course coordinator or the coordinator's delegate (50%).

Project status: This project is taken. The professor has no more '396' projects this term.

How students can apply / Next steps: After all parts of this application form are completed, and the hard copy is signed by the professor and the student, bring this application form and your unofficial transcript to Prof. Gregory Marczynski during office hours, who will review/approve as the course coordinator for MIMM 396 (Microbiology) or MIMM 397 (Immunology).

Ethics, safety, and training: Supervisors are responsible for the ethics and safety compliance of undergraduate students. This project involves: Animal subjects.