The publication of the human genome was an incredible feat, requiring nearly 15 years of research and over $2 billion. In addition to providing unprecedented insight into our genome architecture and function, this project drove the invention of powerful tools to more deeply study and understand genomes. Remarkably, in OUR laboratory today, we can sequence a human genome overnight for approximately $2000. We can deeply mine gene expression in organs, tissues and even in single-cells. We can characterize and quantify mutation rates as low as 1 mutation in 100 million nucleotides. We have high-throughput tools than enable us to do transcriptomic analyses on hundreds of samples at a time, and powerful bioinformatic pipelines to make sense of these complex data sets. The pace of science in genomics has been truly astounding. The mission of the GReAT lab is to harness these ground-breaking tools and approaches to implement transformative ways to study the toxicology of chemicals and their ability to cause disease.
Overall, our research program uses state-of-the-science whole genome sequencing applications to explore how chemical exposures impact the genome, and develop new approaches to use this information in risk assessment. The program straddles academic and regulatory sciences, encompassing two main thematic areas. The first, toxicogenomics, uses genomic methodologies to characterize and predict toxicological mechanisms and effects. With a focus on high-throughput transcriptomics, our research team explores the toxicity of environmental chemicals and how transcriptomic data can best be used to inform health hazards and risk. The second thematic area, environmental mutagenesis, addresses how chemicals damage DNA and chromosomes to cause mutations. This is critical since mutagenesis can lead to cancer and inherited genetic diseases. Our research applies the most cutting edge sequencing tools to study how chemicals cause genotoxicity. One particular focal area is discovering the causes and consequences of mutations in germ cells (sperm and egg) that can lead to inherited genetic effects.
WE ARE EXTREMELY GRATEFUL FOR FUNDING PROVIDED THROUGH THE CANADA RESEARCH CHAIRS PROGRAM, THE CANADIAN FOUNDATION FOR INNOVATION, THE ONTARIO RESEARCH FUND, THE NATURAL SCIENCES AND ENGINEERING RESEARCH FUND, AND THE BURROUGHS WELLCOME FUND. AS WELL, OUR PARTNERS ARE FUNDED THROUGH HEALTH CANADA'S GENOMICS RESEARCH AND DEVELOPMENT INITIATIVE, THE CHEMICALS MANAGEMENT PLAN, AND FUNDING PROVIDED DIRECTLY THROUGH THE WATER AND AIR QUALITY BUREAU, THE CHEMICAL AND ENVIRONMENTAL HEALTH MANAGEMENT BUREAU AND THE EXISTING SUBSTANCES RISK ASSESSMENT BUREAU.
Current projects:
Characterizing mechanisms of toxicological action for data-poor priority pollutants in Canada using novel model systems and transcriptomic methodologies (NSERC Discovery Grant)
PI: Carole Yauk
We’re using cutting-edge genomic tools to modernize how chemical safety is assessed in Canada. Thousands of chemicals in our environment remain data-poor (untested and poorly understood) because traditional toxicity tests are slow, costly, and don’t reveal how chemicals cause harm.
Our team is developing transcriptomic (gene-expression–based) methods to fill these gaps. By analyzing how human cells respond to chemicals at the molecular level, we can identify mechanisms of toxicity, predict hazards, and support smarter regulatory decisions.
This program is training the next generation of regulatory toxicologists and data scientists. Together, we’re creating tools that make chemical testing faster, more informative, and more humane—helping regulators, industry, and green chemists design safer products for the future.
Application of error-corrected Next-Generation Sequencing for assessing the mutagenic effects of environmental and occupational exposures in human populations (Genomics Research & Development Initiative, Health Canada)
PI: Francesco Marchetti; Co-Applicant: Carole Yauk
We’re working with Health Canada scientists to bring next-generation genomics into human biomonitoring. Every day, people are exposed to chemicals, pollutants, and occupational hazards that can cause mutations. Conventional DNA sequencing is too error-prone to detect these rare changes in humans, but new error-corrected sequencing (ecNGS) methods can.
This project applies ecNGS to measure mutations in people most at risk: firefighters, children exposed to air pollution, and patients recovering from chemotherapy. By pinpointing when and where mutations occur, we can better understand how age, environment, and occupation influence genetic health. And together, we’re building the scientific foundation for regulatory decisions that protect future generations.
Revolutionizing genotoxicity testing and assessment through the use of a novel error-corrected sequencing technology
PI: Carole Yauk; Co-PIs: Paul White and Francesco Marchetti
We have won the Burroughs Wellcome Fund Innovations in Regulatory Sciences Award! We are very excited to get started with this international project that brings together uOttawa, Health Canada and collaborators from the Health and Environmental Sciences Institute to modernize how mutagenicity testing is done. The project will investigate how new error-corrected sequencing technologies that have unparalleled accuracy in mutation detection may be used to complement and eventually replace conventional mutagenicity tests used in toxicology. We will also examine how analysis of clonal expansion of cancer driver genes may serve as a biomarker for predicting the potential for chemicals to be carcinogenic.
Overall, our research program uses state-of-the-science whole genome sequencing applications to explore how chemical exposures impact the genome, and develop new approaches to use this information in risk assessment. The program straddles academic and regulatory sciences, encompassing two main thematic areas. The first, toxicogenomics, uses genomic methodologies to characterize and predict toxicological mechanisms and effects. With a focus on high-throughput transcriptomics, our research team explores the toxicity of environmental chemicals and how transcriptomic data can best be used to inform health hazards and risk. The second thematic area, environmental mutagenesis, addresses how chemicals damage DNA and chromosomes to cause mutations. This is critical since mutagenesis can lead to cancer and inherited genetic diseases. Our research applies the most cutting edge sequencing tools to study how chemicals cause genotoxicity. One particular focal area is discovering the causes and consequences of mutations in germ cells (sperm and egg) that can lead to inherited genetic effects.
WE ARE EXTREMELY GRATEFUL FOR FUNDING PROVIDED THROUGH THE CANADA RESEARCH CHAIRS PROGRAM, THE CANADIAN FOUNDATION FOR INNOVATION, THE ONTARIO RESEARCH FUND, THE NATURAL SCIENCES AND ENGINEERING RESEARCH FUND, AND THE BURROUGHS WELLCOME FUND. AS WELL, OUR PARTNERS ARE FUNDED THROUGH HEALTH CANADA'S GENOMICS RESEARCH AND DEVELOPMENT INITIATIVE, THE CHEMICALS MANAGEMENT PLAN, AND FUNDING PROVIDED DIRECTLY THROUGH THE WATER AND AIR QUALITY BUREAU, THE CHEMICAL AND ENVIRONMENTAL HEALTH MANAGEMENT BUREAU AND THE EXISTING SUBSTANCES RISK ASSESSMENT BUREAU.
Current projects:
Characterizing mechanisms of toxicological action for data-poor priority pollutants in Canada using novel model systems and transcriptomic methodologies (NSERC Discovery Grant)
PI: Carole Yauk
We’re using cutting-edge genomic tools to modernize how chemical safety is assessed in Canada. Thousands of chemicals in our environment remain data-poor (untested and poorly understood) because traditional toxicity tests are slow, costly, and don’t reveal how chemicals cause harm.
Our team is developing transcriptomic (gene-expression–based) methods to fill these gaps. By analyzing how human cells respond to chemicals at the molecular level, we can identify mechanisms of toxicity, predict hazards, and support smarter regulatory decisions.
This program is training the next generation of regulatory toxicologists and data scientists. Together, we’re creating tools that make chemical testing faster, more informative, and more humane—helping regulators, industry, and green chemists design safer products for the future.
Application of error-corrected Next-Generation Sequencing for assessing the mutagenic effects of environmental and occupational exposures in human populations (Genomics Research & Development Initiative, Health Canada)
PI: Francesco Marchetti; Co-Applicant: Carole Yauk
We’re working with Health Canada scientists to bring next-generation genomics into human biomonitoring. Every day, people are exposed to chemicals, pollutants, and occupational hazards that can cause mutations. Conventional DNA sequencing is too error-prone to detect these rare changes in humans, but new error-corrected sequencing (ecNGS) methods can.
This project applies ecNGS to measure mutations in people most at risk: firefighters, children exposed to air pollution, and patients recovering from chemotherapy. By pinpointing when and where mutations occur, we can better understand how age, environment, and occupation influence genetic health. And together, we’re building the scientific foundation for regulatory decisions that protect future generations.
Revolutionizing genotoxicity testing and assessment through the use of a novel error-corrected sequencing technology
PI: Carole Yauk; Co-PIs: Paul White and Francesco Marchetti
We have won the Burroughs Wellcome Fund Innovations in Regulatory Sciences Award! We are very excited to get started with this international project that brings together uOttawa, Health Canada and collaborators from the Health and Environmental Sciences Institute to modernize how mutagenicity testing is done. The project will investigate how new error-corrected sequencing technologies that have unparalleled accuracy in mutation detection may be used to complement and eventually replace conventional mutagenicity tests used in toxicology. We will also examine how analysis of clonal expansion of cancer driver genes may serve as a biomarker for predicting the potential for chemicals to be carcinogenic.
