DAVID Y. THOMAS

VIPER, the lentiviral IPPER platform for drug discovery in trafficking diseases. IPPER-accelerated development of pharmacological correctors for cystic fibrosis

Challenge: Drug discovery by high-throughput screening of candidate compounds faces challenges and needs the development and validation of specific platforms. An example of complex diseases that would benefit from such platforms is cystic fibrosis, a lung disease caused by genetics and aggravated by air pollution. An immediate response of bronchial epithelial cells to pollution is the downregulation of CFTR from the cell … Read More

DAVID Y. THOMAS

Development of pharmacological correctors for Alpha-1 antitrypsin deficiency (ATD) using VIPER

Challenge: Drug discovery by high-throughput screening of candidate compounds is usually limited in efficacy as their functional potential is not assessed in relevant biological systems, such as patient cells, during this first selection; new platforms are needed that enable functional testing within specific biological systems. An example of protein trafficking that would benefit from such platforms is Alpha-1 antitrypsin deficiency (ATD), an orphan disease, whose behaviour in the endoplasmic reticulum (ER) is complex, rendering the design of therapeutic candidates difficult. Solution: The primary goal … Read More

*CARL HANSEN

A Screening Technology to Improve the Discovery of Function-Modifying Antibodies Against Membrane Protein Targets

Challenge: G-protein-coupled receptors (GPCRs) are the largest family of cell surface receptors and represent an important class of targets that could be modulated by antibody (Ab)-based therapeutics. However, finding function-modifying antibodies against GPCRs remains a challenge due to the difficulty of preparing purified antigens, poor immunogenicity, small extracellular loops and low expression levels on cells. Solution: The team has developed … Read More

DAVID JUNCKER

A 150-plex affinity proteomics platform for high throughput and high content phenotypic cell screening

Challenge: Proteins are the main effectors of cell activity and cardinal indicators of cell phenotype and response to stimuli such as drugs.  Whereas sequencing technologies currently allow for broad and efficient genomic and transcriptomic profiling, multiplexed protein detection technologies are either prohibitively slow and expensive, limited in scope due to reagent cross-reactivity, or both.  Critically, phenotypic drug screening would greatly … Read More

*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