'Dasatinib conjugates in CLL therapy- mechanism of action' - ANAT 396 Undergraduate Research Project Application Form

Supervisor's Name: Chantal Autexier + Lawrence Panasci

Supervisor's Email: chantal.autexier [at] mcgill.ca

Supervisor's Phone:

Supervisor's Website:

Supervisor's department: Anatomy and Cell Biology

Course number: ANAT 396 (Anatomy and Cell Biology)

Term: Fall 2013-2014

Project start date: Tuesday, September 3, 2013

Project end date: Tuesday, December 3, 2013

Project title: Dasatinib conjugates in CLL therapy- mechanism of action

Project description (50-100 words suggested):

This project will be co-supervised by Dr. Lawrence Panasci and Dr. Chantal Autexier

B-cell chronic lymphocytic leukemia (CLL) is characterized by actively dividing Blymphocytes in the lymph nodes and bone marrow as well as the accumulation of quiescent lymphocytes in the peripheral blood of affected patients. During treatment, the enzyme-mediated repair of DNA damage can induce resistance to chemotherapeutic drugs. Even if combinations of chemotherapy with immunotherapy have shown higher response rates and longer duration of responses, they can be associated with poor tolerability characterized by deterioration of immune functions leading to infections. Thus, there is an urgent need to find curative treatments in chronic lymphocytic leukemia. Dr. Panasci’s laboratory has previously demonstrated that ZRF-4, a combimolecule incorporating imatinib (c-abl inhibitor) plus a chlorambucil-like alkylating agent was more active than the individual components in killing chronic lymphocytic leukemia (CLL) cells obtained directly from patients. Now, Dr. Panasci's lab is investigating a new combi-molecule incorporating a dual Src/c-abl inhibitor (Dasatinib) with a chlorambucil-like alkylating agent. As demonstrated by cytotoxic assay (MTT), these new combi-molecules (AL758 and AL816) are much better than individual components in killing CLL lymphocytes in vitro. The student will perform Western blots and flow cytometry analysis to assess the molecular pathways leading to cell death.

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): 50% final report + 50% evaluation of laboratory performance.

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

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