plansdor@bccrc.ca

Department:	Terry Fox Laboratory (@ the BCCRC since 1986)
Research Role:	Senior Scientist
Postdoctoral Fellows:	Geraldine Aubert Ester Falconer Mark Hills Evert-Jan Uringa
Graduate Students:	Julie Brind'Amour Nathan Corbett Michelle Decker Kathleen Lisaingo Shelley Miller Ján Tkác
Other lab members:	Steven Poon Liz Chavez Lindsey Laycock Mike Schertzer Cam Smith Gayle Thornbury Irma Vulto
Education:	MD, Erasmus University Rotterdam, 1976 PhD (Experimental Hematology), University of Amsterdam, 1985
Birthplace:	Netherlands
Phone:	604-675-8135
Fax:	604-877-0712

Research Interests:

Please visit our new website at  www.terryfoxlab.ca

The major focus of the research in my laboratory is on the role of genetic instability in aging and cancer. Ongoing studies are very diverse in nature, ranging from molecular studies on the role of helicases in the genomic stability of guanine-rich DNA (using C.elegans as a model) to studies of chromosome ends (telomeres) in the biology of normal and malignant cells. An area of specific interest is the role of telomeres and telomerase in stem cells and lymphocytes.

Telomeres are characterized in all vertebrates by TTAGGG repeats and associated proteins. Telomeres protect chromosome ends from fusion and degradation. The loss of telomere repeats appears to limit the proliferation of normal human somatic cells. Loss of telomere function results in apoptosis or replicative senescence or, in very rare instances, in genetic instability that accelerates malignant progression. We have developed novel tools to measure the telomere length in individual cells and individual chromosomes. Quantitative fluorescence in situ hybridization techniques are used to address questions about the role of telomeres in normal aging, tumor progression and specific genetic, hematological and immune disorders.

The interest in telomere biology originates from our previous work with purified blood-forming stem cells. For these studies we developed techniques to purify stem cells based on monoclonal antibodies, multiparameter fluorescence activated cell sorting techniques and magnetic cell separation techniques (for information on large scale cell separation techniques based on technology developed in my lab see   ). We showed that purified human and murine stem and progenitor cells from tissues at different stages of development display marked differences in functional properties. Subsequently, we found that, in humans, such functional differences coincide with measurable changes in telomere length. These observations support the idea that the number of times normal human (stem) cells can divide is restricted by the number of telomeric repeats on specific chromosomes. Recently, we obtained a grant from the Canada Foundation for Innovation to set up a Stem Cell Centre in Vancouver. This grant will allow us to build several new cell sorters and related infrastructure (in collaboration with Dr. Ger van den Engh in Seattle) in the new BC Cancer Research Centre (under construction now with completion expected at the end of 2004).

Current studies focus on the molecular mechanisms of telomere attrition in relation to DNA replication and repair in normal and malignant cells. Such studies include manipulation of known and novel pathways involved in telomere biology and function using lentiviral mediated gene transfer into lymphocytes and various stem cells. You can acess some of our papers as PDF files following this link.

Research Link:

 Research Link for Dr. Peter Lansdorp