Genome Canada – Health Research BC

Development of 3D-printed cardiac organoids for -omics applied to personalized medicine

Our project, made possible with matched funding from Michael Smith Health Research BC, has been funded by Genome Canada’s Canadian Biotechnology Innovation and Commercialization program. This is a BC-based project, in collaboration with Axolotl Biosciences of Victoria. Axolotl is a start-up specializing in producing bioinks for 3D-bioprinting of stem cell-based tissues for applications in disease modeling. In this project, we will develop a bioink meant for stem cell-based heart tissues, to allow us to study heart diseases.

In the Laksman lab, we use personalized stem cells to produce heart tissues for in vitro studies. These stem cells are often from individuals with heart rhythm diseases such as atrial fibrillation, and who may have genetic variants of interest. Using our custom-engineered imaging system, we can measure several properties of the heart tissues at the same time – including both electrical and physical properties of the tissue. The ability to 3D-print heart tissues using a novel bioink will increase the speed and consistency of our studies, and enable high-throughput applications such as drug screening.

To carry out this work, we will use our multi-parameter imaging system in combination with studies of gene expression, and we will identify bioink formulations that produce 3D tissues that more closely resemble adult human hearts than current heart tissue models. This will have potential value in both drug discovery and drug toxicity assays. Ultimately, this project will allow us to identify therapies for patients.

Longitudinal, Deep-Phenotyped Pediatric Databank of Medical and Drug Therapy Outcomes

This sequencing project will enable improvements to drug safety and effectiveness for children by making genomic data on their responses and adverse reactions to various medications more widely accessible to researchers and health regulatory agencies.

Abstract: This project will leverage the existing resources of the Canadian Pharmacogenomics Network for Drug Safety (CPNDS) to bring a pediatric component to the Pan Canadian Genome Library and allow CPNDS to continue its work in making medications safer for children locally, nationally and internationally. Over the past 20 years, the CPNDS has collected DNA and biological samples from over 12,350 patients together with comprehensive demographic and clinical data that characterize their responses to over 100,000 medication uses and over 10,000 severe adverse drug reactions. This number is remarkable given that pediatric diseases like cancers are rare and severe adverse drug reactions are rare occurrences as well. Some patients have more than 40 years of longitudinal data. These patients were recruited and enrolled from 14 academic health centres in geographically diverse locations across eight provinces in Canada (British Columbia, Alberta, Saskatchewan, Manitoba, Ontario, Quebec, Nova Scotia and Newfoundland). This funding is critical for the continuation of this network.

This project has four primary objectives to support the Pan-Canadian Genomics Library (PCGL):

1. Contact previously recruited patients in the CPNDS databank and re-consent them for inclusion of their de-identified clinical and genomic data into the Pan-Canadian Genomics Library (PCGL)

2. Continue to prospectively recruit and enroll patients at our 10 existing study sites over the course of this four-year project (n=4,000). This additional recruitment will be conducted through the lens of significantly enhancing inclusion, diversity, equity and accessibility (IDEA) of the cohort. These samples are being added to ensure that future research beyond this project has a richer and more diverse database of clinical and genomic data to work with.

3. Improve the genomic data holdings from genome-wide genotype typing data (GWAS) to whole-genome sequencing data – short-read sequencing will be conducted for n=10,985 and long-read sequencing will be conducted for n=1,000. This will allow for much more in-depth investigations of drug-induced harm.

4. Conduct genomic analyses using the generated whole-genome sequencing data to explore and identify biomarkers that are predictive of drug-induced harm associated with seven severe adverse drug reactions experienced by pediatric oncology patients in Canada while facilitating dialogue and engaging with the multidisciplinary team assembled for this project. The generation of this data will facilitate research and innovation to improve drug safety and effectiveness in children by making these data more widely accessible to researchers from academic, charitable organizations, health centres, for-profit private companies and health regulatory agencies.

Link: https://genomecanada.ca/project/longitudinal-deep-phenotyped-pediatric-databank-of-medical-and-drug-therapy-outcomes/

CanProspECT program – Canadian Prospective Epitope Compatibility for Transplant

Almost a million Canadians suffer from progressive disease of a vital organ, leading to premature debility and death. The complex care these patients need creates some of our most demanding health challenges, with the economic burden exceeding $10 billion per year. Recent medical advances in transplanting cells and organs have extended the lives and improved the health of many patients. However, transplant is still a high-risk, high-cost procedure. Only around 5,000 patients receive new transplants each year, of which most grafts fail prematurely.

Researchers are working with Canadian Blood Services, the national coordinator of transplant services, to propose a visionary genomics-based solution for better matching donors and recipients for kidney transplants. This solution implements a world-first epitope-based program and aims to reduce patients’ risk of organ rejection, minimize toxic immune suppression, and eliminate the need for lifelong immunosuppressive therapy. The project will be tested in British Columbia, building on previous Genome-Canada-funded work exploring the role of antibody-mediated rejection in graft failure and the key epitopes (the part of an antigen molecule that our immune systems recognize) on the donor human leukocyte antigen molecules responsible. When extended to all of Canada, the project conservatively estimates a benefit of $100 million through preventing hospitalization, premature graft loss and death.