Current Projects (Spring 2012)
completed projects are presented in my publications list.
SARCOMA
- Su L, Poulin NM, Goytain A, Underhill TM, Nielsen TO.
Mechanisms of oncogenesis in translocation-associated sarcomas. Active
research program.
Following up on gene expression profiling and tissue microarray
results, my lab is investigating the role of transcription
factors and repressors of differentiation in synovial sarcoma and related
diseases, the complexes they form, how they are connected to epigenetic
changes in gene promoters and how these cancer-specific changes can be inhibited.
Supported by the Michael Smith Foundation for Health Research and the Canadian Cancer
Society.
- Nielsen TO, Bramwell V, Eisenhauer E, Chu Q. Histone
deacetylase inhibitors for the treatment of translocation-associated sarcomas.
Clinical trial, closed to accrual.
Our work over the past 7 years has culminated
in a clinical trial, for which I am coordinating correlative sciences.
The preclinical work has been supported by grants from the Terry Fox Foundation,
the Canadian Cancer Society and CIHR. The Investigational New Drug trial
(NCICCTG IND.200) of the agent SB939 is funded by the
NCIC-Clinical Trials Group. This trial
is now undergoing outcomes analysis and molecular marker studies.
- Huntsman DG, Nielsen TO,
Jamshidi F, Sorensen PHB, Underhill TM, Yip S, Landsdorp P, Hirst M, Hansen
C, Aparicio S, Marra M. The genomics of form fruste tumours. Active
research program.
Working with a group of the top cancer researchers
in British Columbia, we are employing
next
generation sequencing technologies to identify the causative molecular
abnormalities of a group of rare, under-explored cancers, including several
types of sarcomas. We feel the opportunity to identify the molecular cause
of these diseases is particularly good, and if successful will lead quickly
to new diagnostics and therapies. Funded by the
Terry Fox Research Institute. We are
grateful for support from our colleagues at several institutions including
Toronto's University Health Network and the MD Anderson Cancer Center in
helping us to assemble sufficient collections of some rare tumor types.
- Lee CH, Clarkson P, Jones
K, Wang YZ, Poulin NM, Nielsen TO. CSF1 pathway inhibitors
in tenosynovial giant cell tumors and leiomyosarcoma. Active research
program.
Building on our
identification of a novel translocation that drives the oncogenesis
of tenosynovial giant cell tumor we are developing models to test new targeted
treatment options. We are also making a special effort to test leiomyosarcomas.
Previously supported by the Cancer
Research Society, this work is now supported by a full operating grant
from the Canadian Institutes
of Health Research.
This international consortium, brought together by a targeting
funding initiative from the Liddy Shriver
Sarcoma Initiative, will allow our institutions to assemble the world's
largest collection of myxoid liposarcoma specimens and models. We will use
these resources to try to understand the molecular biology of this disease,
and to develop new therapeutic strategies.
BREAST CANCER
- Nielsen TO, Liu S, Leung
S, Gao D, Shepherd L, Bramwell V, Pritchard K, Levine M, Whelan T, Chia SK, Gelmon K, Brunner N, Tykjaer-Jorgensen
C, Ejlertsen B. Predictive value of biological
breast cancer classifiers in North American and European patient series.
Active research program
Following up on our work using the "big series"
of 4000 cases from the
Genetic Pathology
Evaluation Centre, we can, with good accuracy, subtype breast cancer
into Luminal A, Luminal B, HER2 and Basal subtype using immunohistochemistry
and
Nanostring
technologies. We are applying this strategy to formalin-fixed, paraffin-embedded
blocks supplied by the
NCIC-Clinical
Trials Group and in collaboration with the
Danish Breast Cancer Group,
Ontario Institute for Cancer Research
and the
Alliance for Clinical
Trials In ONcology cooperative groups. Multiple projects are underway,
testing if this subtyping predicts response to cytotoxic drug, endocrine
and radiation therapies. Supported by an unrestricted educational grant from
sanofi-aventis Canada, collaborator
funds from the
Susan Komen Foundation
and the
Canadian Breast
Cancer Foundation.
- Nielsen TO, Liu S, Barry G, Cheang MCU, Leung S, Bernard
PS, Perou CM, Ellis M. Biological-based
classification of breast cancer by qRT-PCR and multiplexed color-coded
probe pairs. Manuscripts submitted.
Our group was part of the successful consortium
(Washington University, University of Utah, UNC-Chapel Hill, and UBC) funded
by the U.S. National Institute of Health to adapt molecular signatures of
breast cancer for clinical use. We developed qRT-PCR and Nanostring nCounter-based
assays identifying
the
intrinsic molecular portraits of breast cancer originally discovered
using DNA microarrays. A panel of 50 genes (the PAM50 classifier) can do
this on formalin-fixed, paraffin-embedded standard and archival tissue specimens,
and is currently being tested to identify how it can predict patient outcome
and response to therapy. Originally funded by the U.S. National Institute
of Health (
Strategic
Partnering to Evaluate Cancer Signatures), this work has now moved to
a second developmental phase in partnership with
Nanostring Technologies, including
work done in partnership with US, Canadian
and European groups.
- Choo J, Chow C, Perou CM, Aparicio S, Dunn SE, Cheang MC, Nielsen TO. Biomarkers for basal breast cancer. Active
research program.
My
most
cited paper to date presented a practical, easy and highly specific
way to detect the clinically-important basal-like subtype of breast cancer.
Drawing on the latest gene expression profiling data and on our tissue microarray
validation resources, we are testing additional antibody biomarkers to
see if we can develop an even more sensitive surrogate immunopanel, that
retains specificity and remains easy to apply. Supported by my senior scholar
grant from the
Michael Smith Foundation for
Health Research and by the
Canadian Breast Cancer
Foundation, BC/Yukon Division.
- Nielsen TO, Polley
M-Y, McShane L, Hayes DF, Dowsett M.
Clinical implementation of Ki67 as a
breast cancer biomarker. Active research program.
Following an international workshop held
at the Breakthrough Breast Cancer Research Centre in London, we have been
entrusted to organize a multiinstitutional study of interobserver variability
and specimen type-specific scoring methodology to address some unanswered
questions about how to actually assay the best immunohistochemical marker
of proliferation, Ki67. This biomarker has potential value in diagnosis,
prognosis, prediciting the best anticancer drug, and monitoring the success
of therapy for breast cancer. Supported by the
North
American Breast Cancer Group.
I'd be happy to discuss any of these topics with you!
torsten(nospam)@mail.ubc.ca
Last modified 2012.4.09
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