Biological Nano Electrical Mechanical System (BioNEMS) Research Group

Dr. W.J. (Chris) Zhang meets semi-regularly with researchers from the U of S Colleges of Medicine, Pharmacy and Neutrinos, and Engineering. The collaborative research on the subject of radiofrequency ablation (RFA) provides new scientific basis to guide the operation of surgeon in tumor removal. Currently, the size of the tumor that can be removed by RFA is about 3 cm. BioNEMS Group research results, along with the device, have a high potential to enable removal of tumors larger than 3 cm. Several on-going researches include: (i) development of a combined RFA and irreversible electroplating (IRE) method to ablation of tumors to improve precision in ablation, (ii) development of 3D cell responses under strain, and (iii) molecular self-regulated responsive insulin delivery to diabetes patients.

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Cannabinoid Research Initiative of Saskatchewan (CRIS)

The aim of this interdisciplinary research group is to obtain scientific evidence about the application of cannabinoids and cannabis derivatives to humans and animals, for health, disease, and disorders.

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The Immunology Research Group (IRG) was formed in 2003 by a consortium of the University of Saskatchewan's immunologists. They comprise a large number of scientists from five departments at the U of S, as well as five associated research or diagnostic organizations. IRG's mandate is to foster immunology research within our community that is recognized both nationally and internationally for its excellence. Given the deeply integrated nature of immunology with so many other disciplines, IRG researchers focus their efforts on an array of specialties, including tumour and transplant immunology, allergy and asthma, infectious diseases, inflammation, toxicology, basic immunology, and immunoregulation, at the molecular, cellular, and organismal levels.

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Dr. Price’s interdisciplinary research program and CRC in Radiochemistry at the University of Saskatchewan is working to create new chemical reagents as tools for the creation of next-generation diagnostics and treatments of diseases such as cancer. The Price lab is creating a library of modular and versatile chemical tools that are being deployed to improve many aspects of modern and clinically used radiopharmaceutical drugs to solve real-world problems plaguing molecular imaging and radionuclide therapy of diseases. These chemical tools are being painstakingly designed and synthesized to be modular, much like LEGO, to provide maximum value and utility.

Many new radiopharmaceuticals are based on proteins, usually in the form of antibodies, peptides, or protein domains (nanoparticles can possess similar chemistry and properties as well). To create these, one must assemble several key components which each serve specific functions, and each can be swapped/optimized through synthetic organic and bioconjugation chemistry. These components include 1) a chelator to quickly bind and stably hold radioactive metal ions to enable PET imaging or radionuclide therapy, 2) a linker to provide physical space and/or other chemical structures between the chelator and the bioconjugation reagent, typically to give the targeting vector ample space to engage with its receptor “dock” or to improve water solubility, or with the Price lab linkers to even provide new functions, 3) the bioconjugation reagent/moiety to quickly and selectively provide a strong chemical linkage between the chelator-linker (or dye/drug-linker) and the protein, and 4) the targeting vector such as a peptide or antibody to provide selective receptor-based targeting to many different diseases and biological markers.

Core projects in the Price lab have been designed to solve or improve many of the practical issues and deficiencies of modern radiopharmaceuticals via the first three of these four key components: the chelators, functional linkers, and the bioconjugation reagents. These deficiencies have been identified by Dr. Price over his career through the evaluation of academic and clinical data on modern molecular imaging and radionuclide therapy agents. From observing and studying the problems with current radiopharmaceuticals, Dr. Price is trying to identify the chemical origins of these problems and utilize his expertise in the USask Chemistry department to solve them. Dr. Price’s lab is creating new chemical tools which are modular and are designed with unique structural properties which have been hypothesized to improve properties of radiopharmaceuticals in the key areas outlined above.

The cancer-targeted radiopharmaceuticals that Dr. Price is creating are selective and sensitive. As radioactive imaging agents they are being designed to provide exquisitely accurate and sensitive early detection of cancer, and as radioactive therapeutics they aim to have fewer side effects than many of the highly toxic and non-selective standard chemotherapy drugs still used today. These types of drugs can be thought of as “smart drugs”, as they are able to selectively bind to cancer cells while ignoring healthy cells. Some of these radioactive agents are used for positron emission tomography (PET) nuclear imaging to provide non-invasive and quantitative data about a patient’s individual cancer burden, which is currently the only effective way to apply the principles of personalized medicine.

Local collaborations at the U of S include the Canadian Light Source synchrotron (CLS) to study metal-chelate binding properties with collaborators Drs. Graham George and Ingrid Pickering. A recently awarded SHRF Collaborative Innovation Development grant with Drs. George, Pickering, Price, and Dmitriev will provide seed money to start a collaboration looking at the role of copper and zinc in Alzheimer’s disease. Dr. Price is also collaborating closely with Drs. Chris Phenix and Ron Geyer, where they are attempting to improve delivery and selectivity of highly toxic chemotherapeutic drugs by using the cellular machinery of cancer (enzymes) against itself. Dr. Price has also been recently awarded a CIHR Project Grant with Drs. Andrew Freywald and Franco Vizeacoumar to generate cutting-edge personalized medicine for triple negative breast cancer by combining genotype-directed cancer therapy with radioactive antibodies. Drs. Price and Phenix have also recently been awarded a SHRF Collaborative Innovation Development grant with collaborator Dr. Mike Moser, a Surgeon at the Royal University Hospital and NanoKnife cancer treatment specialist, to create a new type of prodrug to be used with NanoKnife treatment to improve efficacy in pancreatic cancer.

Funding sources for Dr. Price’s research are crucial and greatly appreciated, including the Natural Sciences and Engineering Research Council of Canada (NSERC), Canada Research Chairs (CRC), Canada Foundation for Innovation (CFI), Saskatchewan Health Research Foundation (SHRF), Canadian Institutes of Health Research (CIHR), the Fedoruk Centre, and startup funds from the University of Saskatchewan.
To learn more, please access Price Research Group's website.

To learn more, please access Price Research Group's website.

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Proteomics Research in Interactions and Structure of Macromolecules (PRISM)

PRISM brings together a large group of scientists with diverse research programs with protein science as a common denominator. The research themes of PRISM members are related to the understanding and utilization of molecular processes in the cell and in cell-cell interactions, and include:

• signal transduction and molecular mechanisms of cancer
• protein-protein interactions and molecular mechanism of pathogenicity
• molecular mechanisms of immunity and vaccine development
• small molecular inhibitors as therapeutic agents

PRISM maintains the Protein Characterization and Crystallization Facility (PCCF), which provides access to specialized equipment guided by knowledgeable PhD-level staff.

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Based on existing research strengths at the U of S, the Tissue Engineering Research Group (TERG) was formed in 2007 with the aim of developing advanced technologies for the production of tissue/organ scaffolds for various tissue engineering application. TERG currently includes more than 10 professors, clinicians, and scientists from both life sciences and engineering. The research collaborations among TERG ranges from the development of tissue scaffolds to various TE applications including the repair of articular cartilage, bone, teeth, peripheral nerves, and spinal cord, as well as in the treatment of myocardial infarction, cerebral aneurysms, and cancer.

The strategies being developed include efforts to engineer novel scaffolds with controlled composition and properties optimized for given applications, to promote cell function and tissue regeneration, and to antagonize inhibitory effects occurring in damaged tissues/organs or target cancer stem cells. These strategies will be creatively integrated to achieve combined or synergistic effects for a given TE application through tests in culture dishes, animal models, and, eventually, human patients.

The TERG research also aims to develop synchrotron-based imaging technologies to track the success of scaffolds in the TE applications. The innovative aspect of TERG research rests on the development of novel scaffolds, creatively integrated strategies, and unique synchrotron-based imaging, which combined will have profound long-term impact on the health and welfare of patient populations around the world.

For more information, please [fa-icon email] Contact TERG Leader, Dr. Daniel Chen.

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The Bacterial Physiology & Genetics Research Cluster is comprised of 2 labs that collaborate and perform important topic-related research activities:

Kerri Kobryn's laboratory studies the biochemistry and molecular biology of the Lyme Disease spirochete Borrelia burgdorferi. The Lyme disease spirochetes are unique among human pathogens in having a linear chromosome and plasmids terminated by unusual hairpin telomeres. The lab primarily studies the enzyme, ResT, which forms hairpin telomeres with a view towards eventual rational design of Borrelia-specific drugs. ResT is related to proteins that in other bacterial species control chromosome segregation.

Peter Howard's laboratory studies the molecular biology of toxin secretion by Gram-negative bacteria and structure, function and biogenesis of the outer membrane. In Gram-negative bacteria, the peptidoglycan cell wall is a significant structural barrier for outer membrane protein assembly, and the lab investigates the mechanism of peptidoglycan reorganization to enable membrane protein assembly and toxin secretion.

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The Biomedical and Environmental Research Cluster is a group of basic scientists and clinicians from the Departments of Anatomy and Cell Biology, Agriculture and Bioresources, Medicine, Microbiology and Immunology, Pathology and Laboratory Medicine, the College of Pharmacy and the School of Public Health.  The lab houses the CFI funded National Agricultural Industrial Hygiene Laboratory (NAIHL), and the Mass Spectrometry facility.  Researchers undertake a diverse range of research initiatives in biomedical and environmental health research.

The Biomedical and Environmental Research Cluster has celebrated their great work with an annual 2^nd Floor Research Day (2017 and 2018) together with the Cardiopulmonary Cluster (2D40), and welcome collaboration with other investigators.

 For more information about researchers, shared equipment and most recent publications please visit the Biomedical and Environmental Research Cluster website.

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The Cancer Cluster occupies more than 6,000 sq. ft. of space on the 4th floor of the new Academic Health Sciences Building at the University of Saskatchewan.  This group includes seven Principal Investigators studying various aspects of cancer cell biology, providing high caliber interdisciplinary training in the study of cancer cells utilizing a blend of cell biology, biochemistry, molecular biology, protein structure-function, enzymology, cell-based assays, and animal models to answer fundamental questions about the nature of cancer cells and how this information could be used to identify and validate new targets for therapy. 

Containing four Research Scientists from the Saskatchewan Cancer Agency and three Researchers from the University of Saskatchewan, the Cancer Cluster's combined group size is about 35 people, including: graduate students, post-doctoral fellows, research associates, research technicians, summer students and undergraduate research project students.

To learn more, please access the Cancer Cluster website.

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The Cardiopulmonary Research Cluster is a group of scientists and clinicians conducting a wide range of research at the University of Saskatchewan. The cluster contains eleven faculty members, together with their students and research staff, from the Departments of Biochemistry, Medicine, Pharmacology and Physiology.

For more information, please visit Cardiopulmonary Cluster - 2D40.

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The Drug Discovery and Development Research Group (DDDRG) is a collaborative research group of 14 researchers from the College of Pharmacy and Nutrition and the College of Medicine. The group advances research leading to therapeutic applications for new and existing drugs as well as the discovery of bioactive compounds, such as found in Saskatchewan agricultural products. 

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The Imaging and Development Cluster is an interdisciplinary group of 13 clinicians and scientists, hailing from 5 departments in the Colleges of Medicine and Dentistry, and in the School of Physical Therapy. Using innovative imaging techniques to reveal mechanisms of disease, the cluster collaborates widely in the Colleges of Kinesiology, Arts and Science, Veterinary Medicine, and Engineering, highlighting a cross-disciplinary approach. In the past 5 yearsit has enjoyed great success, obtaining 50 grants totalling more than $20M from CIHR, NSERC, and other funding agencies, publishing over 150 scholarly papers, and trained more than 150 highly-qualified personnel (students, residents, and technicians).

Making great use of our local resource, the Canadian Light Source synchrotron, a majority of cluster members work to develop new means to assess and treat skeletal and neural disorders. With lab facilities that satisfy molecular biology, cell culture, and histology needs, the cluster has unique imaging components, including microCT and OPT imagers, with top-shelf image processing software.  The exact projects carried out in each cluster lab varies from skeletal development in mouse, chick, and fish embryos to neurological disease in human brains to blood vessel changes in disease, but a common interest in innovative imaging techniques pulls them all together.

Please Contact Brian Eames if you're interested in how the Imaging and Development cluster might work together with you.

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The U of S currently conducts vigorous research into providing innovative treatments for infectious diseases using molecular design of new drugs. Using this research and investments in unique synchrotron technologies at the Canadian Light Source, biological and containment facilities at the Vaccine and Infectious Disease Organization (VIDO) with InterVac, the Molecular Design Research Cluster has submitted a proposal for a Canada Excellence Research Chairs (CERC) position, which would provide a focal point for a team-driven aggressive attack on these infectious diseases that threaten our society.

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The Neuroscience Research Cluster is a group of basic scientists and clinicians conducting neuroscience-related research at the University of Saskatchewan. Here, they share contiguous laboratory and office space within the new Health Sciences building and as a team are making great progress in understanding what causes certain brain disorders and how best to treat patients who suffer from these brain disorders. Twenty-one faculty members and over sixty trainees and research staff work in the areas of mental health, psychiatric disorders, and related illnesses, including:

• Stroke
• Epilepsy
• Neurodegenerative disorders
• Multiple Sclerosis
• Alzheimer's disease
• Pain
• Diabetes

To learn more, please access the Neuroscience Research Cluster website.

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The Virology & Immunology Research Cluster is comprised of 4 labs collaborating and performing health research related to the topics of virology & immunology:

Linda Chelico's lab examines the host intrinsic immunity to HIV-1 infection and the origins of mutations in cancer cells. These seemingly disparate topics are unified by the enzyme family involved in both processes, the APOBEC family of deoxycytidine deaminases. APOBEC enzymes modify cytosine in single-stranded DNA to promutagenic uracil, which enables a variety of physiological functions (inhibiting HIV-1) and malfunctions (cancer mutagenesis). We have characterized the biochemical features that enable mutagenesis of HIV-1 and human DNA, which have implications in both the treatment of HIV-1 and cancer.

The central focus of Joyce Wilson's laboratory research is the study of virus-host interactions between HCV and the infected cell. Of particular interest are interactions between HCV and the micro RNA pathway of the cell, specifically miR-22 that helps HCV to replicate. This is an unusual function for a miRNA, which normally suppresses translation and promotes degradation of RNAs. The lab is undertaking structure-function and virology studies to dissect this relationship.

Research in Popi Havele's laboratory concentrates on understanding the biology and physiological function of the CD8 T Cell. His team has found that the naturally occurring CD4:CD8 Ratio is a defining and predictive parameter of the specific immunity induced by antigen. Our findings relate to the mechanism of CD4 T Cell Differentiation, mouse strain dependent differential CD4:CD8 Ratio, and age dependent differential CD4: CD8 Ratio resulting in preferential Induction of Th2 immunity in Neonates.

Peter Bretscher's laboratory studies mechanisms responsible for self-nonself discrimination and immune class determination and immune responses in autoimmunity, to tumours, and in chronic infectious diseases, and strategies of vaccination.

Newest cluster member Kerry Lavender's research focus is viral immunology. Dr. Lavender developed the TKO-BLT humanized mouse model for the study of viral pathogenesis and human immunity to human pathogens such as HIV-1. The model is particularly suited for the in vivo assessment of new therapies, particularly those that require an extended period of evaluation such as HIV-1 cure strategies. Currently, the lab’s primary focus is to understand and harness the unique properties of individual interferon alpha subtypes in order to develop new therapeutic strategies against HIV-1 infection.

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