completed projects are presented in my .
In 2023, we secured a highly competitive 5 year operating grant
from the Canadian
Institutes for Health Research to continue our research
program in synovial sarcoma . My group
will be characterizing the enhancer landscape in synovial sarcoma
(collaborating with Martin Hirst, to develop novel technologies
for detection of enhancer-RNAs), and working with Michael
Underhill to characterize and apply a mouse model for synovial
sarcoma to investigate epigenetic and other novel treatment
strategies.
The Terry Fox Marathon of Hope represents a national initiative to accelerate Canada's transition to a future of precision oncology -- treatment directed to the specific underlying molecular mechanisms driving each individuals' tumor biology. Our group has, in collaboration with prominent sarcoma researchers at the University of Toronto, been funded to generate a public resource of genomic, transcriptomic, epigenetic, histologic and clinical information about sarcomas. We are currently focussing on synovial sarcoma, chondrosarcoma, and a spine tumor type called chordoma, with additional work planned on clear cell sarcoma, myxoid liposarcoma, endometrial stromal sarcoma and leiomyosarcomas.
Early in my career, working with Matt van de Rijn in a
Stanford-UBC collaboration, we identified macrophage colony
stimulating factor rearrangements and CSF1R overactivity as the
driver event in TGCT, a neoplasm that destroys joints in young
people. This work nspired the development CSF1R inhibitors as a
new treatment for this disease, one of ASCO's
advances of the year in 2019. Recent work from our groups
have reopened questions into cooperating mutations and into where
and how CSF1 is expressed, the answers to which we believe will
guide optimal use of these new treatments. Supported by a Terry
Fox Research Institute Program Project in collaboration with
David Huntsman, we've recently re-opened our TGCT research program
and our collaborations with Stanford and Leiden.
Supported by the
friends and family of Josh Lombardi, including through the BC
Cancer Foundation, we have opened a dedicated research
program in DSRCT, a dangerous form of sarcoma that arises in the
abdominal cavity of young adults. Having surveyed the literature,
what others are doing and what the scientific and clinical needs
are, we are working on potential targeted therapies, including by
generating a much-needed conditional mouse model.
Gregg Morin, Yueyang Li, Angela Goytain, Stephen Chia, Miguel Martin, Gian Negri, Seti Boroomand, Torsten Nielsen. Development of novel breast cancer biomarkers through proteomics.
We have been funded by the Canadian
Cancer Society to work with Gregg Morin's recently-developed
SP3-CTP proteomics technology: developing proteomics-based
profiles on pathology biopsy specimens and validating their use as
potential clinical tests. We have been awarded additional funding
from the Canada Foundation
for Innovation to identify, source and install new
technologies for in situ validation of cancer biomarkers. With
these funds, we have obtained a nanoString Digital Spatial
Profiler, Leica autostainers, Aperio ScanScope and Zeiss Axioscan
hardware and associated image analysis software that actively are
being implemented for this program of research.
Beginning with some of the first molecular profile work in breast cancer, our group has been developing practical clinical tests for the major molecular subtypes of breast cancer, tests that can determine biology, guide risk assessment and therapy. This has led to some of my most cited papers which have related to development of immunohistochemical panels for Luminal and Basal subtypes, and the PAM50 gene expression profile. The latter was transferred to the nanoString platform and has been cleared for use by the FDA, Health Canada and EU as a validated clinical test known as Prosigna. Ongoing work seeks to extend these findings – better IHC panels, identification of additional low risk groups who can safely undergo therapeutic de-escalation, and predictive tests.
Torsten Nielsen, Elahe Shenasa, Katherine Rich, Heikke Joensuu,
Ali Bashashati. Optimizing triple negative breast cancer
therapy based on immune cell morphology.
In our grant funded by The
Cancer Research Society we are using digital image analysis
technology being developed by biomedical engineering collagues to
assess immune infiltrates that, within a
clinically high-risk but molecularly heterogeneous group of
breast cancers, may (a) have such a good prognosis that
chemotherapy may not be needed, or (b) benefit specifically from
capecitabine treatment as opposed to conventional chemotherapy,
checkpoint or PARP inhibitors.