Congratulations to Charbonneau Investigators on successful CIHR Fall 2024 Project Grants
We are thrilled to share that several members of the Arnie Charbonneau Cancer Institute were successful in the Fall 2024 CIHR Project Grant competition. Approximately $3.7M was awarded institute-wide over five grants, with an overall success rate of 50% (national average was 17.2%).
Associate Professor, Departments of Oncology and Community Health Sciences
Professor, Department of Community Health Sciences
Jill Tinmouth
Professor, Department of Medicine, Temerty Faculty of Medicine, University of Toronto
Co-Investigators: Winson Cheung, Doreen Ezeife, Tamer Jarada, Jonathan Loree, Dylan O'Sullivan, Arlinda Ruco, Matthew Warkentin
Project Background:
The REFRAME Project- Rapid Evaluation FRAmework for the Modification of Cancer ScrEening Guidelines
Cancer screening has already saved the lives of hundreds of thousands of Canadians. However, who and how we screen for cancer has evolved over time. There are new tests, new needs, and new emerging disease trends. One example of these changes is the increase in early-onset colorectal cancer (eoCRC), among Canadians diagnosed before age 50 - the current recommended age to start screening. In the US, they have already revised their guidelines to screen at age 45 and in some cases as young as 40. In Canada, our healthcare system and how we run screening programs is very different than the US. Making a change to guidelines can have a major impact on scarce health resources, therefore many additional pieces of research and evidence are required for provinces and territories to make proper, informed decisions on whether they should change their screening programs. This grant would provide the evidence for these decisions using our Rapid Evaluation FRAmework for the Modification of Cancer ScrEening (REFRAME) Guidelines. In this project, we will develop the tools to generate the information needed for the provinces to make these types of decisions. We will develop several automated processes to rapidly synthesize what we know about the new questions in cancer screening, how much it would cost to make any changes, and what would be needed across provinces to enable these changes. For this project, we will use eoCRC as the lead example, but we will generate a sustainable, reproducible, and reusable tools that could be used to evaluate other screening changes such as for cervical, lung, breast, as new tests emerge and cancer trends change with our evolving population. Thus, the successful completion of this project has clear next steps and broad ongoing impact in cancer control. Upon the completion of this project, provinces would be equipped with the information they need to make important decisions for patients. REFRAME offers a short time-to-impact in cancer control.
Duration: 3 years
Professor, Department of Oncology
Co-Investigators: Paul Arora, Kelvin Chan, Navdeep Dehar, Doreen Ezeife, Christie Farrer, Alind Gupta, Tamer Jarada, Vishal Navani, Stuart Peacock
Project Background:
Generating Synthetic Data for Oncology Use Cases to Facilitate Multi-Jurisdictional Research
Many cancers are rare, and within certain tumor types, specific biomarkers and mutations can be even rarer. Therefore, conducting adequately powered analyses and achieving meaningful results can be increasingly difficult. Frequently, data must be pooled from multiple sources or regions for research to occur. However, current data legislations are often prohibitive, thus making it challenging to share data across provincial and territory borders. Synthetic data, which are artificially generated to mimic the statistical properties and structures of real data without revealing any patient information, offers a promising solution to current legal barriers and ethical challenges associated with data sharing. The overall objective of this study is to use machine learning and statistical models to generate and validate high quality synthetic data for specific oncology scenarios, namely: (1) sarcomas, which is a rare cancer; (2) ALK and ROS mutated lung cancers, which are rare genetic variants; and (3) rural patients, who are frequently marginalized. All three groups face significant barriers to treatment advances due to their persistent under-representation in clinical trials as well as their heightened privacy concerns due to their small sample sizes. Therefore, synthetic data may help accelerate research in these underrepresented populations by creating datasets that can be shared more easily across regions, combined together to improve sample sizes, and rebalanced to enhance their diversity and representativeness Rigorously generated and validated synthetic datasets hold immense potential to revolutionize research and expedite progress by addressing the critical issues of data sharing and privacy, scarcity, and diversity. The lessons gained from this proposed study can be leveraged to replicate our work in other jurisdictions, facilitate broader implementation for the use of synthetic data, and expand the reach and impact of our findings beyond Canada.
Duration: 4 years
Professor, Department of Physiology and Pharmacology
Co-Investigators: Lauren Davey, Douglas Mahoney
Project Background:
Cellular immunotherapies of cancer have been under intense development for the past decades. One such therapy is called chimeric antigen receptor (CAR)-T cell therapy where the patient's T cells are removed from the blood, modified in the laboratory to recognize and attack tumor cells, and then given back to the patient. Despite the success of CAR-T cell therapy for treatment of some blood cancers, nearly half of patients either do not respond to the treatment or relapse. To date, research in the CAR-T cell therapy field mostly focuses on how researchers can improve performance of the cells by modifying the genetic component of the CAR receptor to be more efficient. In contrast, we aim to investigate how the patient's microbiome (and small molecules produced by the microbiome) alter the function of the CAR-T cells. The gut microbiome and microbial metabolites have been found to modulate and improve the anti-cancer function of T cells in another type of cancer immunotherapy, called immune checkpoint blockade therapy. Similarly, differences in the patient's microbiome composition may be one of the key extrinsic underlying factors determining responsiveness to CAR-T cell therapy. We have recently identified microbes which aid in immune checkpoint blockade therapy of solid cancers and our preliminary data suggests that the same bacterial species can also aid CAR-T cell function in preclinical animal models of B cell acute lymphoblastic leukemia. In this research project we will further identify the mechanisms involved in this process and confirm the findings in patients undergoing CAR-T cell therapy. Our study will serve as a basis to develop microbial based therapeutics to promote the efficacy of CAR-T cells to ultimately transform non-responding patients into responding patients.
Duration: 5 years
Associate Professor, Department of Biochemistry & Molecular Biology
Project Background:
The human genome, the blueprint for every cell, is encoded by over 3 billion base pairs of DNA. To fit this large amount of DNA into the nucleus, it needs to be condensed into chromatin. In this structure, DNA is wrapped around histone octomers to form nucleosomes that tightly pack together. However, this condensed chromatin creates a barrier to essential cellular DNA metabolism processes, including replication, transcription, and damage repair. Chromatin remodelers are ATPase enzymes that interact with other proteins to regulate and control the access of DNA metabolism machinery to DNA by altering the compaction of DNA. The human protein HELLS is a chromatin remodeler that, in normal cells, plays essential roles in establishing the most condensed form of chromatin, called heterochromatin, and regulating access to heterochromatin to facilitate processes such as DNA transcription for cell growth and proliferation, and DNA damage repair. However, HELLS is mutated in a rare disease called ICF-4, is overexpressed in many cancers, and a role for HELLS in regulating the ability of cancer cells to maintain a stem cell-like state or differentiate into more mature cells has been established. As such, HELLS is a potential target to develop new cancer therapies. The aim of this research project is to use integrated biochemical, structural biology, and cell biology assays to determine the molecular mechanisms for how HELLS is regulated by protein interaction partners and post-translational modifications, which are chemical modifications of proteins that occur after they are made. Results from the project will deepen our fundamental understanding of the essential cellular processes HELLS is involved in, provide insights into how regulation and malfunctioning of HELLS contributes to diseases including cancer, and provide a molecular basis to design therapies targeting HELLS to treat cancer.
Duration: 5 years
Professor, Department of Oncology
Harriet Richardson
Associate Professor, Department of Public Health Sciences, Queen's University
Co-Investigators: Linda Balneaves, Alan Bates, Margot Burnell, Harvey Chochinov, David Clements, Jean Mathews, Michael Mckenzie, Ronal Shore, Claudio Soares, Wei Tu, Monnica Williams
Project Background:
People living with advanced cancer often struggle with feelings of loss of home and meaning in life (demoralization), anxiety about end of life, fear of death, and symptoms of depression; all of which can compromise overall quality of life and worsen their final months. While some therapies have been developed to help people cope and prepare for end of life, they are not always effective, quick, or long-lasting. In combination with supportive therapy, the psychedelic drug psilocybin (from magic mushrooms) has had promising results as a fast-acting and long-lasting treatment in small trials conducted in the United States to date. In this study, we will investigate the impact of a single, high-dose of psilocybin along with meaning-focused supportive mindfulness therapy on 120 people with advanced cancer suffering from demoralization, in a multi-site trial across Canada. To do so, we will train a group of publicly-funded therapists in this modality, who will then be in place at cancer centres across Canada to continue offering the therapy, should it prove effective. We will also engage administrative policymakers in these cancer centres and Health Canada to further facilitate future implementation. Throughout the study, we will employ best practice principles of equity, diversity, and inclusion in composing our study team, choosing therapists, and recruiting patient participants.
Duration: 2 years
