Our cells remove damaged or nonfunctional proteins through a small protein called ubiquitin, which attaches to target proteins and signals their destruction. In many diseases, ubiquitin does not work as it should. Dr. Sachdev Sidhu of the University of Toronto is using an innovative high-throughput molecular genetics engineering platform, which is unique in the world and has attracted intense interest from industry and academia, to enable the rapid and cost-effective development of highly specific and potent ubiquitin-like molecules. These molecules attach to key, cancer-associated enzymes of the ubiquitin system, to block or enhance their function. The project will enable the discovery of new drug targets, speed up drug development and generate effective anti-cancer drugs with fewer side effects, all of which should be of great socio-economic benefit to Canadians.
Often in cancer it’s the spread of the cancer to other areas of the body, a process called metastasis, that kills. This is particularly the case with two highly lethal types of cancer, medulloblastoma (MB), the most common malignant brain tumour in children, and pancreatic adenocarcinoma, the fourth leading cause of cancer deaths in Canadians. Recent results from the lab of Dr. Michael Taylor of The Hospital for Sick Children have shown that the biology of the metastases is extremely different from the primary tumour, making it unlikely that treatments developed to treat the primary tumour will work on the metastases. Dr. Taylor has teamed with Dr. Rama Khokha (Princess Margaret Cancer Centre) to develop and deploy unique tools to discover the drivers of metastasis, helping to improve survival rates of Canadians with these deadly human cancers.
Many illnesses, such as cancer or cardiovascular disease, leave physical evidence in our bodies, called biomarkers. Spotting these biomarkers early would make it possible to begin treatment with personalized, targeted therapy, or even prevent disease entirely. Solid-state nanopore-based devices can do this, but are too expensive for widespread use. Dr. Tabard-Cossa’s laboratory has pioneered a technique to fabricate nanopore devices more rapidly and at substantially lower cost than present-day technology. They are integrating the devices into a disposable cartridge within compact platforms offering comprehensive sample-in, answer-out capability. The lab is positioned to develop a point-of-care prototype that can be used in the lab and the clinic, resulting in significant economic and health benefits for Canada.
“De novo” sequencing, or constructing an individual’s genome from his or her own data alone (as opposed to comparing it to a reference genome), is a formidable task, akin to assembling a jigsaw puzzle comprising hundreds of millions of small blank pieces. Drs. Si Lok, Stephen Scherer, and their colleagues from The Hospital for Sick Children are developing a new “mate-pair” technology that would overcome the financial and logistical barriers to de novo sequencing by linking sequences to one or more other reads in precisely known orientations and distances. Mate-pair technology would create a high-resolution backbone to enable de novo sequencing to be carried out in a single simple step. This new adaptation of mate-pair sequencing is a disruptive technology that could supersede all current methods of de novo sequencing, thereby representing a leap forward in many areas of research and, ultimately, in healthcare.
SickKids’ Drs. Cynthia Hawkins and John Racher and NanoString Technologies are merging their individual strengths to develop additional tools for diagnosing cancer in children. Funded through Round 6 of Genome Canada’s Genomic Applications Partnership Program, they are working to create tools that will deliver key information in a targeted, cost-effective and timely way. This initial work will focus on low-grade glioma (brain tumours), leukemia and soft-tissue sarcoma, for which no comprehensive tests currently exist. This tool will improve survival times and quality of life for children with cancer, reduce healthcare costs and generate licensing revenue, which will be shared between the partners.
Non-small cell lung cancer is the most common type of lung cancer. Specific genetic mutations in a patient’s tumour can determine which drug will work best for that patient. Dr. David Stewart, from The Ottawa Hospital and the University of Ottawa, is working with the Eastern Ontario Regional Laboratory Association (EORLA) to develop an assay that can accurately detect important genetic mutations in the very small biopsy samples from patients with advanced lung cancer. The assays will test for multiple genetic variations at once, for a more timely result than is possible with current sequential testing strategies.
Intracerebral hemorrhage (ICH) is a form of brain hemorrhage responsible for 10 per cent of all strokes. Dr. Xiao-Yan Wen, director of the Zebrafish Centre for Advanced Drug Discovery (ZCADD) and his team used genomics-driven research tools to identify several existing drugs already approved by the US FDA that have shown the ability to prevent ICH in zebrafish models. In this project, Edge Therapeutics is partnering with Dr. Wen to perform preclinical studies on the most potent anti-ICH molecules known as EZF-0100 for treatment of ICH and brain microhemorrhages (BMH). This may develop a way to administer the drug in a sustained release profile and may also synthesize and test analogs of EZF-0100 to determine the best drug candidate for preclinical development and clinical study in Canada and the US.
96 per cent of people aged 65 or older diagnosed with acute myeloid leukemia (AML) die within five years, as do two-thirds of younger patients. Researchers from University of Toronto and University Health Network and The Hospital for Sick Children (SickKids), partnered with Trillium Therapeutics Inc. have been awarded $3.4 million through Genome Canada’s GAPP to developed SIRPaFc, a novel therapeutic that blocks the “do not eat” signal, freeing the immune system to attack leukemia stem cells. This collaboration between Drs. Wang and Danska and TTI will assist in realizing the commercial potential of this promising discovery.
Not all cells in our bodies are created equal. The differences between cells are important – they cause cells to respond in surprisingly different ways to the same drug treatments. Progress in understanding these difference has been hindered by the lack of effective tools. Drs. Bjerknes and Cheng of the University of Toronto are addressing that need with the aid of Ontario Genomics’ SPARK program. They are developing new methods for accurately tagging individual cells in intact tissues for careful study to measure its genomic status. This work will ultimately render single cell genomics more accessible to labs and researchers.
Dr. Peter Liu of the University of Ottawa Heart Institute discusses his research, which, through a partnership with Roche Diagnostics, is working to develop a novel heart failure biomarker panel that accurately diagnoses and classifies the disease. This solution enables physicians to select the best and the right treatment for individual patients.