I was trained as a synthetic chemist with a focus on inorganic compounds as hypoxic radiosensitizers. In subsequent research positions, I worked on developing new PET imaging agents, sustained delivery of Pt-drugs to potentiate radiation effects in hypoxic cells and identifying anti-malarial agents from natural products. My past training makes me interested in integrating different technologies and scientific concepts to develop innovative solutions for clinical and scientific problems. At BC Cancer, I take a collaborative approach and work with other Scientists from BC Cancer and other institutions on a variety of projects. In the past, I have used non-invasive imaging technologies to better understand tumour physiology during tumour progression and treatment, and more recently have been examining nanoparticle platforms for on-command drug delivery. My technical skills include: synthetic and analytical chemistry, non-invasive imaging (PET-CT and MRI), radiobiology, tumour metabolism, hypoxia and angiogenesis, drug delivery and tumour mapping.

Affiliations

Research Scientist, Department of Experimental Therapeutics, BC Cancer

Adjunct Professor, Division of Pharmaceutics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, UBC

Credentials

Ph.D. in Chemistry, University of British Columbia, Vancouver, British Columbia, 1993

B.S. in Chemistry, University of Victoria, Victoria, British Columbia, 1987

Projects

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.

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
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