Our group is interested in understanding how molecular changes in tumours are manifested in their microenvironment, and whether such changes can be monitored non-invasively to guide treatment strategies. We therefore use molecular techniques in a complementary fashion with non-invasive imaging (positron emission tomography (PET) and magnetic resonance imaging (MRI)) to study clinically relevant tumour models from the bottom up and top down. These studies are done through the core PET imaging program at the BCC and the MRI program at UBC.

Present projects in the group include a strong collaboration with the Gates group (SFU) to develop novel nanoparticles made of soft (e.g. lipids or proteins) that incorporate gold or iron oxide. The soft materials will store drug and protect it until needed. The metallic component will be used with external sources of energy to break down the lipid or protein matrix and subsequently release the drug. Our group is currently working with Scientists at TRIUMF to use exotic radiation beams for this purpose. In a separate project, we are using our imaging technologies and collaborating with physicists and theoretical mathematicians (SFU and UBC) to develop numeric models that describe the forces and energies required for cell movement and transport of particles within the cytosol.





Selected Publications

Regulation of pH by Carbonic Anhydrase 9 Mediates Survival of Pancreatic Cancer Cells With Activated KRAS in Response to Hypoxia.

Gastroenterology, 2019
McDonald, Paul C, Chafe, Shawn C, Brown, Wells S, Saberi, Saeed, Swayampakula, Mridula, Venkateswaran, Geetha, Nemirovsky, Oksana, Gillespie, Jordan A, Karasinska, Joanna M, Kalloger, Steve E, Supuran, Claudiu T, Schaeffer, David F, Bashashati, Ali, Shah, Sohrab P, Topham, James T, Yapp, Donald T, Li, Jinyang, Renouf, Daniel J, Stanger, Ben Z, Dedhar, Shoukat

Irinophore C™, a lipid nanoparticulate formulation of irinotecan, improves vascular function, increases the delivery of sequentially administered 5-FU in HT-29 tumors, and controls tumor growth in patient derived xenografts of colon cancer.

Journal of controlled release : official journal of the Controlled Release Society, 2015
Neijzen, Robert, Wong, May Q, Gill, Navdeep, Wang, He, Karim, Tamanna, Anantha, Malathi, Strutt, Dita, Waterhouse, Dawn, Bally, Marcel B, Tai, Isabella T, Ng, Sylvia S W, Yapp, Donald T

Irinophore C, a novel nanoformulation of irinotecan, alters tumor vascular function and enhances the distribution of 5-fluorouracil and doxorubicin.

Clinical cancer research : an official journal of the American Association for Cancer Research, 2008
Baker, Jennifer H E, Lam, Jeffrey, Kyle, Alaistair H, Sy, Jonathan, Oliver, Thomas, Co, Steven J, Dragowska, Wieslawa H, Ramsay, Euan, Anantha, Malathi, Ruth, Thomas J, Adam, Michael J, Yung, Andrew, Kozlowski, Piotr, Minchinton, Andrew I, Ng, Sylvia S W, Bally, Marcel B, Yapp, Donald T T


Patient Derived Xenografts (PDX) for Pancreatic Cancer

A panel of unique PDXs from clinical tumour samples were established and used to study metronomic gemcitabine’s treatment effects and the interactions between tumour stroma and cancer cells in situ. The original tumour lines have been merged into the BC Pancreatic Centre’s (BCPC) xenograft and in vitro bank of pancreatic cancer related biological matter. New tumour lines are being established, characterized and linked to the patient’s treatment history and outcome. The tumour lines are available freely to Scientists interested in pancreatic cancer research through the BCPC.

Sequential Therapies

The effects of low-dose/high frequency or sustained drug delivery on vascular function in the tumour are of interest to develop sequential dosing therapies. In these projects, liposomal irinotecan and metronomic gemcitabine were shown to transiently improve vascular function and decrease hypoxia leading to a window of therapeutic opportunity with a second drug or radiation therapy. We also showed that functional imaging could be used to identify these opportunities.

HER-2 Breast Cancer

HER-2 overexpression in breast cancer is a marker for treatment resistance and orchestrates distinct tumour biology. Our group developed novel, very stable linkers for labeling trastazumab with 64Cu for in vivo imaging of HER-2 breast tumours. In a separate, but related study, the metabolic activity and hypoxic status of HER-2 breast tumours was also examined.

Novel PET Agents

Detecting the production of radical oxygen species in situ has potential as a novel biomarker.  A novel compound (FaSu) for PET imaging of ROS activity and glutamine flux in cancer cells was developed and validated with TRIUMF. FaSu is of clinical interest for assessing tumour response to treatment and/or inflammatory processes.

Non-Invasive Detection of Tumour Hypoxia

In collaboration with Scientists and Clinicians at TRIUMF and the BCC, we initiated the first 18F-EF5 PET clinical studies in Canada for lung cancer and prostate cancer. Further studies to examine hypoxia in ovarian, and head and neck cancers have also been carried out. Pre-clinical studies carried out by my group formed the impetus for the clinical studies. Our group also supported the production 18F-EFT for clinical use.

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