Meet the Researchers

Research Interests

The Anderson lab has identified a gene that promotes breast cancer metastasis and is currently working to develop a new drug to inhibit this novel target. We hope this new inhibitor can then be used to block breast cancer metastasis as an additional treatment option for our patients.

Dr. Anderson’s team has also identified a new combination of drugs that when used together is very effective at low doses providing more breast cancer cell killing than when high doses of each drug are used alone. This research raises the exciting possibility that we may be able to use low doses of two drugs to provide a very effective breast cancer treatment, and because the doses needed are lower, the side-effects for patients would be reduced, improving the quality of life for our patient’s undergoing treatment.

Publications

Research Interests

The Chamberlain Lab is interested in the development of new tools and assays to improve the selection of treatment regimens for cancer patients. To do this we use a multitude of approaches to stratify how patients will respond to different cancer therapies, ranging from determining new biomarkers for cancer sub-classification to directly testing chemotherapies on patient-derived tumour organoids.

Current Research Directions:

1) Identifying molecular profiles that predict patient responses to cancer therapies

This project will analyze public and in-house generated data to develop molecular profiles of different tumour types that correlate to how the tumour reacts to a specific cancer therapy. The aim of this project is to go beyond identifying the simple mutations and variances in tumours that are actionable with targeted drug treatments by identifying profiles of gene expression that further subdivide these tumours into high and low responders to a treatment. This work will lead to new understanding of how different tumour pathways interact with each other. Using this information, we will be able to discover new biomarkers for the responsiveness of a tumour to a treatment and develop better combinational cancer therapies to treat poorly responding patients.

2) Developing the next generation of tumour organoids for drug testing

There has been great interest in the development of 3D cell culture of cancer cells to better understand the development of tumours and how they respond to drug treatments. Several groups have found that these tumour organoid cultures are better mimics of how the cells respond compared to 2D cultures. However, most of these tumour organoid cultures are still very primitive as they are mostly spheroids of cancer cells grown in a basement membrane extract (BME). These spheroids often are started from a single cell suspension of cancer stem cells so do not have the diversity of cell types found in the tumours. Although, cells from the tumour microenvironment can be added back into the tumour organoid culture, BME gels are an exceptionally soft and weak gel that do not support the growth of large numbers of cells. Therefore, we will develop the next generation of tumour organoid models based on the methods and principles developed in the field of tissue engineering.

3) Develop chemotherapy testing methods on patient-derived tumour organoids

The information and methods from the first two projects will be used to develop better in vitro methods of cancer therapy testing using patient-derived cells in the next generation of tumour organoid models. We will develop methods to generate the required cell inputs from patient samples to form the tumour organoids and then study their response to different chemotherapy agents as a tool for precision medicine.

Publications

Research Interests

Historically cancer has been studied and treated based on body parts. However, the advent of cost-efficient genome sequencing has revealed that only a handful of genes are frequently altered in a high percentage of tumors. A key message from these studies is that therapeutic approaches should aim at the genetic basis rather than the tissue of origin. This knowledge and the availability of highly selective inhibitors of gene products, promises a genotype-directed cancer therapy. Our lab is interested in developing such a genotype-directed cancer therapy for solid tumors by applying a basic biological concept called synthetic lethality. In effect, any genetic alteration that can cause selective-lethality with an oncogenic or a tumor suppressor mutation can be potentially translated into a therapeutic target. This will ultimately enable personalized medicine in which patients having disease of similar biological origin will likely benefit from a specific drug treatment. Our long-term goal is to build a synthetic lethal network that will enable us to understand the genetic dependencies of cancer cells and define key therapeutic targets.

Publications

Dr. Jim Xiang obtained his M.D. at Medical University of Shanghai, China and his M.S. and Ph.D. at University of Florida in Pathology. After a Post-Doctoral Fellow with Dr. Jaff Schlom at National Cancer Institute in NIH, USA, followed by a Research Assoiate with Dr. Nobu Hozumi at Mt. Sinai Hospital in Toronto, Xiang joined the Cancer Agency in 1990. He has been Senior Scientist in 1995 and Professor, Division of Oncology at the University of Saskatchewan. His research focuses on the molecular Pathway underlying T cell fate and memory for vaccine design and the development of novel immunotherapy for combating various cancers. 

Dr. Xiang’s Lab focuses on (i) studying the molecular mechanism regulating CD8+ T cell fate and memory formation, (ii) assessing the critical role of CD4+ T cell help in CD8+ T cell immunity, and (iii) developing novel HER2- and Gag-specific exosome-targeted T cell vaccines for HER2+ breast cancer and HIV-1 patients.

Research Activities

1. Molecular pathways for CD8+ T cell fate and memory: Understanding the molecular pathway controlling CD8+ T cell fate and memory is critically important in vaccine development and immunotherapy. We recently discover that mannose-6 phosphate receptor (M6PR) specific for lytic granule Granzyme-B (GB) plays a critical role controlling T cell fate. M6PRhigh CD8+ T cells die of GB-mediated lethal hit, while M6PRlow ones survive in the contraction. We further elucidate that pro-inflammation cytokine IL-2 induces M6PRhigh CD8+ T cells while pro-survival cytokine IL-7 stimulates M6PRlow ones differentiating into long-term memory T cells. The IL-2-stimutaed strong activation of mTORC1 up-regulates motor protein KIF13A leading delivery of more M6PR onto cell surface of IL-2-activated CD8+ T cells susceptible for GB-mediated killing, and vis-à-vis for the IL-7-stimulated weak mTORC1 activation. We are currently studying the molecular pathway regulating the memory T cell differentiation of IL-7-induced M6PRlow CD8+ T cells.
2. A new concept "Th-APC": A long-standing paradox in cellular immunology concerns the conditional requirement for CD4+ T cells in priming of CD8+ cytotoxic T lymphocyte (CTL)responses. We found that CD4+ Th cells can acquire synapse-composed pMHC I and II and CSM from APCs via trogocytosis, and become Th‐APCs capable of stimulating CD8+ T cell response and memory.Therefore, this new conceptual advance may have great impacts in antitumor and autoimmune responses. We are currently studying molecular mechanisms of CD4+ T cell help in CD8+ T cell immunity and memory.
3. Exosome-targeted T cell-based vaccines: Based upon the new concept of “Th-APC”, we developed CD4+ T cell‐based vaccines using polyclonal CD4+ T cells with uptake of Ag‐specific dendritic cell (DC)-released exosomes (EXO), and demonstrate that the novel vaccine is capable of directly stimulating potent CD8+ CTL effector and memory responses, counteracting CD4+ Tr‐mediated immune suppression, and converting CTL exhaustion via its CD40L signaling activation of mTORC1 pathway in chronic infection. We are currently developing HER-2/neu-specific and HIV-1 Gag-specific exosome-targeted T cell vaccines for treatment of HER-2/neu-positive breast cancer and HIV-1 patients.

Publications