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Colleen C. Nelson, Ph.D.

Senior Scientist, The Prostate Centre at VGH
Associate Professor, Department of Surgery, University of British Columbia
Head, Gene Array Facility
Director, Genome BC Microarray Platform

UBC cross-appointments: Department of Pathology and Laboratory Medicine; Genetics Program; Experimental Medicine Program

Jack Bell Research Centre
2660 Oak St.
Vancouver, BC
Canada V6H 3Z6
Office: 604 875-4282
Fax: 604 875-5654
E-mail: ccnelson@interchange.ubc.ca

   

Research Interest

The research interests in my laboratory are centered on understanding the role of aberrant gene expression in prostate cancer progression, with a particular emphasis on the mechanism of androgen-specific gene regulation and the progression to androgen independence. To study the progression of prostate cancer we use prostate tumour models that can be analyzed both in vitro and in vivo. In mice the human prostate tumours are grown as subcutaneous zenografts and progress to androgen independence in a predictable time frame after castration, as monitored by the production of PSA as a surrogate marker of progression. This model system provides an excellent opportunity to study changes in gene expression during this pathway with gene microarray technology. Using these systems we are able to readily observe changes in gene expression patterns correlating with progression and treatment. Genes of interest are studied by observing the effects of over expression or down regulation of the gene at the molecular level to characterize their role in progression process. Genes that may be causative of progression or interfere with therapeutic efficacy can be knocked out using antisense oligonucleotide technology and are being tested as new potential therapeutics for advanced prostate cancer.

Another set of projects in my laboratory investigates the DNA-binding specificity of steroid receptors and other transcription factors and the mechanisms that result in their discrete modes of transcriptional regulation. We are currently analyzing a number of transcription factors that are upregulated during prostate cancer progression and identifying the cascades of genes that they regulate. Another focus of my laboratory is to identify substances in environmental contaminants, such as PCBs and pesticides, and dietary factors that influence steroid hormone action. We have developed a tissue culture assay which is highly responsive to agonists and antagonists of the androgen and glucocorticoid receptors. Compounds that demonstrate steroid receptor interference in vitro, are investigated in vivo using transgenic systems and tumour model systems to determine their potential affects on the development and progression of prostate cancer.

To characterize gene expression changes at this comprehensive level, we have established a state of the art gene array facility in the Prostate Centre that I direct in which we create and analyze human and mouse arrays containing tens of thousands of genes. The gene array facility is optimized for studying human and mouse gene expression patterns. Beyond our cancer studies we also collaborate with the Heart and Stroke Network, The UBC Brain Centre, The Prostate Network, The Herbal Medicine Network, Complementary Therapy Network and the Centre for Disease Control and others investigators in infectious diseases. The facility was created with the flexibility to study a variety of other technologies emerging in the array field including the examination of DNA protein interactions, and antibody arrays for protein expression analysis. This facility has nucleated the Genome BC Array Platform that I also direct and has expanded tremendously to serve the needs of a wide variety of scientists with interests including foresty, fisheries, and the environment.

   

Publications

Ettinger SL, Sobel R, Whitmore T, Akbari M, Bradley D, Gleave ME, Nelson CC. Dysregulation of sterol response element binding proteins and downstream effectors in prostate cancer during progression to androgen independence. Cancer Research 64: 2212-21 (2004).

Gimenez-Bonafe P, Fedoruk MN, Whitmore T, Akbari M, Ralph JL, Ettinger S, Gleave ME, Nelson CC. YB-1 is upregulated during prostate cancer tumor progression and increases P-glycoprotein activity. The Prostate 59:337-49 (2004).

Fedoruk MN, Gimenez-Bonafe P, Guns ES, Mayer LD, Nelson CC. P-glycoprotein increases the efflux of the androgen dihydrotestosterone and reduces androgen responsive gene activity in prostate tumor cells. The Prostate 59: 77-90 (2004).

Gleave M, Nelson C, Chi K. Antisense targets to enhance hormone and cytotoxic therapies in advanced prostate cancer. Current Drug Targets 4: 209-21 (2003).

Mulholland DJ, Read JT, Rennie PS, Cox ME, Nelson CC: Functional localization and competition between the androgen receptor and T-cell factor for nuclear b-Catenin: a means for inhibition of the Tcf signaling axis. Oncogene 22: 5602-13 (2003).

Ralph JL, Orgebin-Crist MC, Lareyre JJ, Nelson CC. Disruption of androgen regulation in the prostate by the environmental contaminant hexachlorobenzene. Environmental Health Perspectives 111: 461-6 (2003).

   
   

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