Colleen C. Nelson, Ph.D.
Senior Scientist, The Prostate Centre at VGH
Associate Professor, Department of Surgery, University of British
Head, Gene Array Facility
Director, Genome BC Microarray Platform
UBC cross-appointments: Department of Pathology
and Laboratory Medicine; Genetics Program; Experimental Medicine
Jack Bell Research Centre
2660 Oak St.
Canada V6H 3Z6
Office: 604 875-4282
Fax: 604 875-5654
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.
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.
is upregulated during prostate cancer tumor progression and
increases P-glycoprotein activity. The Prostate 59:337-49
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
of androgen regulation in the prostate by the environmental
contaminant hexachlorobenzene. Environmental Health Perspectives
111: 461-6 (2003).