Research in my laboratory is focussed on the study of homologous genetic recombination in mammalian cells. Procedures that we use to obtain answers to questions in these areas include techniques in recombinant DNA/molecular genetics, immunological and immunochemical techniques and techniques in somatic cell genetics.
Recombination is the process by which genetic information is exchanged between DNA duplexes. This process causes genomes to undergo structural alterations leading to changes in the linkage relationship between genes or groups of genes. Recombination is important for the assembly and expression of genes, the generation of genetic diversity and the repair of DNA damage. However, recombination can also generate DNA structures, which lead to the development of cancer and other diseases.
The three research goals of my laboratory are,
- to understand the molecular genetic mechanisms of recombination in mammalian cells,
- to understand how defects in recombination contribute to tumorigenesis, and
- to understand the nature of recombination hotspots.
We are presently researching questions pertaining to,
- the mechanism and frequency of recombination in mammalian cells,
- the role of large palindromes in promoting recombination within and between mammalian chromosomes,
- mammalian heteroduplex DNA formation and repair during recombination,
- genetics of strand invasion and 3' end polymerization,
- how DNA sequences act to stimulate recombination (i.e., recombination hot-spots),
- non-crossover mechanisms of homologous recombination,
- the genetic control of recombination (investigation of the role of the Rad52 epistasis group of genes, and the Breast Cancer 2 tumor suppressor gene, BRCA2).
One way we study recombination is by introducing DNA into mammalian cells and then determining how it recombines with its endogenous chromosomaltarget locus. This mode of recombination is called gene targeting. Potentially, gene targeting is an effective form of human gene therapy. We also study recombination as it occurs both within and between mammalian chromosomes. The experimental systems that are in use in our laboratory are yielding information which contributes to our understanding of the recombination process at the molecular level, and its importance in normal and pathological states.
Our research is supported by operating grants from the Canadian Institutes of Health Research (CIHR), and the Natural Sciences and Engineering Research Council (NSERC) of Canada.