*GORDON SHORE

Synthetic lethality platform to discover, test and validate new therapeutic treatment options for cancer

Challenge: In recent years, only 8% of new oncology drugs have been approved for clinical use. One of the major challenges has been matching an appropriate therapeutic strategy to a cancer indication due to the heterogeneity of the disease. Nevertheless, the personalized medicine approach is not a simple process, as each cancer type represents a unique disease that harbors a variety … Read More

*JASON MAYNES

Novel Methods to Evaluate Cardiac Activity of Pharmaceuticals: Identifying New Therapies and Predicting Cardiac Toxicity

Challenge: Current therapies for heart failure primarily relieve symptoms, but most fail to correct organ dysfunction. New therapies, to target and improve cardiomyocyte function, are challenging to develop because of the complex functions of the heart muscle and the difficulty in modeling heart cell behavior. The same problems underlie the difficulty in assessing the cardiotoxic side effects of drugs. There … Read More

*HENRY KRAUSE

Zebrafish High Throughput Screening Platforms for Nuclear Receptor-Related Drug Discovery and Pathway Elucidation

Challenge: With the unique property of nuclear receptors (NRs) to directly interact with genomic DNA and control the expression of genes, nuclear receptors play key roles in both embryonic development and adult homeostasis as well as in many diseases. With a total of 48 different human receptors and 6 epigenetic-regulating cofactors identified, the is still no available screening platform that … Read More

*HENRY KRAUSE

A Zebrafish-Based Platform for Nuclear Receptor Drug Screening and Pathway Discovery in Metabolic Disease and Cancer

Challenge: Nuclear receptors (NRs) are a family of proteins that regulate gene expression in many vital processes such as metabolism, growth and behaviour. They are also implicated in a large array of diseases such as diabetes, Parkinson’s, Alzheimer’s and cancer. Consequently, nuclear receptors represent one of the most important class of targets for existing drugs. However, mainly due to a … Read More

*MICKEY BHATIA

Using Patient’s Blood to Develop a Sensory Neuron-Based Platform to Treat Chemotherapy-Induced Peripheral Neuropathy

Challenge: The sensory neuron damage referred as “Chemotherapy-Induced Peripheral Neuropathy” (CIPN) affects 30-40% of cancer patients in Canada. Sensory neurons transmit information from the brain to every other part of the body allowing movement and awareness of our environment. The deterioration of these cells from chemotherapy causes severe pain often leading to the interruption of chemotherapy treatments. Unfortunately, developing a … Read More

*TERRY HÉBERT

FlAsH-Walk Mapping: An Innovative Step-by-Step Approach to G Protein-Coupled Receptor Conformation Cartography

Challenge: G protein-coupled receptors (GPCRs) are the largest target class for approved drugs. Identification of new drug candidates has relied exclusively on high-throughput assays which track binding properties and are limited to a restricted number of signaling pathways. GPCRs are highly dynamic proteins that undergo numerous conformational changes upon receptor association with ligands and related protein partners. The use of … Read More

STEVEN LAPLANTE

Fragment-Based Lead Discovery: Bridging the Gap Between Screening and Hit-to-Lead Medchem using NMR Affinity Ranking

Challenge: One of the most promising strategies for discovering our future medications is via fragment-based lead discovery (FBLD). FBLD involves the screening of libraries of small molecules to first identify weak binders, essential to activate or inhibit a target protein involved in a particular disease. These binders are then synthetically matured to larger, more potent inhibitors/leads via medicinal chemistry design … Read More

DAVID Y. THOMAS

IPPER, the Integrated Platform for the Pharmacology of the Endoplasmic Reticulum and protein trafficking diseases

Challenge: Endoplasmic reticulum (ER) stress occurs when the folding of secreted proteins within the ER lumen is disturbed. The unfolded protein response (UPR) comprises several mechanisms. These adaptive responses attempt to overcome ER protein folding disturbances to promote cellular homeostasis and cell survival. ER stress and the UPR are implicated in many diseases such as neurodegenerative and cardiovascular diseases, diabetes … Read More

*MICHEL BOUVIER

New GPCR-Specific Biosensor Technology to Monitor Cellular Events Associated with Drugs Efficacy and Side Effects

Challenge: G protein-coupled receptors (GPCRs) form the largest family of cell surface receptors involved in signal transduction of many hormones and transmitters. It follows that drugs targeting GPCRs represent close to 40% of all drugs on the market today. Recent discoveries regarding their function and mechanism of action help pave the way for the development of more selective therapeutics for … Read More

*IGOR STAGLJAR

Acting on membrane protein-protein interactions: Mammalian Membrane Two Hybrid (MaMTH) as an Innovative Technology for Drug Discovery Against Protein- Protein Interactions

Challenge: Membrane proteins, representing approximately one-third of all proteins in a cell, interact with each other and are responsible for a variety of processes, making them attractive therapeutic targets for many diseases such as hypertension, diabetes, neurological disorders and various cancers. In fact, membrane proteins represent 60% of all clinical drug targets, however, they are still extremely difficult to study … Read More