McGill University Health Center		 Molecular Biology Laboratory
of
   Drs. T.Y.K. Chow, Denis Cournoyer and Chantal Séguin
Montreal General Hospital Research Institute
(Hematology)
1650 Cedar Avenue, Montreal, Quebec, Canada, H3G 1A4
Tel: 934-1934 ext. 42428
e-mail: lab@molbio.mcgill.ca
Principal  investigators:

Dr. T.Y.K. Chow Ph.D.

Dr. Denis Cournoyer M.D.

Dr. Chantal Séguin M.D.


 
Some former lab members' projects:

Jean-Philippe Belzile

Sibgat Choudhury

Antonis Karatzas

Paul Kauler

Amin Kerachian


 
Lab stuff & links:
password:



McGill library
NCBI GenBank

Primer3

ATCC Tissue Collections

 Sheldon Biotechnology
 
 
The belief in an external world independent of the perceiving subject is the basis of all natural science. Since, however, sense perception only gives information of this external world or of "physical reality" indirectly, we can only grasp the latter by speculative means. It follows from this that our notions of physical reality can never be final.
                                                                                                          Albert Einstein

 

Terry Chow's Group

DNA Recombination Repair

With the advance of molecular  genetics, it has been found  that processes such as gene targeting, chemo-/radio-sensitivity or resistance in cancer therapy, viral integration into the host genome, and gene therapy do all share a common mechanism known as DNA recombination repair. For example, the gene  replacement mechanism is known to proceed through a DNA double-strand break repair intermediate of the recombination repair process. In our laboratory, the elucidation and the understanding of the protein(s) and their roles in DNA double-stranded break (DSB) repair are our goals.

Using the yeast as the model system, we isolated and characterized a recombination  repair endo-exonuclease that is coded by the RNC1 gene. Over-expression of this endo-exonuclease leads to an increase of homologous recombination frequencies and resistance to chemical adducts and radiation, whereas its absence potentiate the cell to DNA double-stranded break. This enzyme is also expressed  in high amount in cancer cell lines and is one of the first enzymes processing the site of DNA double-stranded breaks for repair. The endo-exonuclease is interacting with other protein(s) to form a recombination  repair protein complex. We are currently dissecting the other protein(s) in this complex in the repair of DNA double-stranded breaks. Human homologues of this endo-exonuclease have already been identified in our laboratory and found biochemically to be the same as for the yeast enzyme. Furthermore, we have identified a small molecule that inhibits the enzyme.  Thus, the endo-exonuclease and its interacting protein(s) is an excellent candidate(s) for over-expression to enhance gene targeting, or inhibition to eliminate chemo/radio-resistance of cells during cancer therapy.

Denis Cournoyer's Group

Gene Therapy

Gene therapy is a very promissing approach to the treatment of inheritted and acquired health disorders. Stable expression of transferred genetic information is, in most cases, best accomplished through the use of gene transfer vehicles (vectors) that integrate in the host cell DNA. Retroviral vectors are the most widely used, and best studied  integrative vectors. In our laboratory, we constructed and tested retroviral vectors expressing genes that in hematopoietic cells confer resistance to different types of antineoplastic and myelosupressive drugs which are commonly used as tumor growth inhibitors during cancer chemotherapy. An increased resistance, and in turn increased tolerance of patient's hematopoietic stem cells to such drugs could reduce the severity of patient's cytopenia and thus improve the quality of life of persons undergoing chemotherapy.

Retroviral transduction does however, carry some risks of insertional mutagenesis. To reduce, or eliminate such risks will require an improved understanding of the mechanisms controlling retroviral  integration. Based on this understanding, we can develop strategies permitting control of vector integration, and redirect it into potentially "safer" sites. The existence of a retroviral "targeting pathway" is yet to be elucidated. Currently we are investigating the potential role of retroviral integrase-interacting cellular proteins in targeting the integration into highly transcribed genes.

Chantal Séguin

Avascular Necrosis

Osteonecrosis (ON) or avascular necrosis (AVN) of the bone can occur when the blood supply to the bone is disrupted and is usually found in areas with terminal circulation. Osteonecrosis of the femoral head (ONFH) is a disabling and progressive condition, which, if untreated, leads to femoral head collapse requiring total hip replacement.  The etiology and pathogenesis of nontraumatic osteonecrosis of the femoral head are not known, but involvement of factors such as steroid administration, chronic alcohol consumption, smoking habits, and abnormal lipid metabolism have been implicated

Our main interest is to study potentially dysfunctional cells leading to ONFH at the level of gene expression in vivo and in vitro models. 

Jean-Philippe Belzile   |   Sibgat Choudhury    |   Dr. T.Y.K. Chow Ph.D.   |  Dr. Denis Cournoyer M.D.
Antonis Karatzas  |  Paul Kauler   |   Amin Kerachian  |  Dr. Chantal Séguin M.D.
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