Uri Tabori

At a Glance

• Research focuses on the study of DNA replication repair deficient cancers to facilitate the translation of biological findings into clinical applications
• Utilizing human patient samples to understand cancer predisposition and to uncover novel tumour subgroups, cancer-specific signatures, biomarkers and gene drivers
• Developing models including genetically engineered and patient-derived xenograft mouse models, as well as induced pluripotent stem cells and differentiated organoids to study tumour evolution, cancer vulnerabilities and to discover early detection, intervention and therapeutic strategies
• Applying bioinformatic computational methods to analyze large datasets obtained from next-generation sequencing and other genomic tools

Short Bio

Dr. Uri Tabori is pediatric oncologist that serves as the Section Head of Neuro-Oncology within the Division of Haematology/Oncology at The Hospital for Sick Children. As a researcher, Dr. Tabori has significantly advanced the understanding and treatment of pediatric brain tumors and DNA replication repair deficient cancers. Throughout his career, Dr. Tabori has been recognized with numerous awards, including the Early Researcher Award from the Ontario Ministry of Development and Innovation in 2014 and the Canadian Cancer Society’s Bernard and Francine Dorval Prize in 2016. He also holds the Garron Family Chair in Childhood Cancer Research. His lab integrates clinical expertise with laboratory and bioinformatics projects to drive discoveries in childhood cancers that can translate into novel therapies.

Research Synopsis

DNA replication repair deficiency (RRD) results from mutations in DNA mismatch repair and/or polymerase proofreading genes, and can occur somatically or be inherited in cancer predisposition disorders such as Lynch Syndrome and Constitutional Mismatch Repair Deficiency (CMMRD). One hallmark of RRD is increased mutational burden which often leads to early-onset and aggressive cancers, particularly in brain tumours including gliomas, that are difficult to manage with conventional therapies.

Dr. Tabori’s lab utilizes patient samples and clinical data, as well as employs molecular biology and mouse genetics to help understand the uniqueness of RRD tumours and how to combat them. Large-scale studies are implemented to analyze patient data in order to characterize RRD pan-cancer incidence and genetic risk factors, leading to the refinement of surveillance strategies and improving management for children with RRD-driven cancers. His lab utilizes advanced genomic technologies that include next-generation sequencing, nanopore sequencing and NanoString to analyze DNA, RNA and methylome of RRD cancers, at single cell resolution. Computational modeling is then used to examine these large datasets to perform genetic, epigenetic, and tumour immune microenvironment analyses to pinpoint key somatic driver mutations, gain insight into RRD-driven tumourigenesis, improve tumour subgrouping, and predict response to immunotherapy. His lab also leverages human models including cell lines, induced pluripotent stem cells and differentiated organoids to uncover biological mechanisms related to RRD cancers, as well as to understand why certain tissues are more vulnerable to developing these tumors.

In addition to understanding tumor biology, several projects explore novel therapeutic strategies against RRD-driven cancers. Given the poor response of these tumours to conventional treatments, his lab has heavily focused on immune-based interventions, including immune checkpoint inhibitors and neoantigen-targeting lipid nanoparticle (LNP) mRNA vaccines, to induce robust T cell response. Additionally, immunocompetent mouse models and CRISPR-Cas9 screening are used to identifying key genetic and immune-related vulnerabilities that influence response to immunotherapy.

Through these efforts, Dr. Tabori’s lab aims to translate research biological discoveries into clinical trials and personalized medicine approaches, improving outcomes and quality of life for pediatric cancer patients worldwide.

International Replication Repair Deficiency Consortium

Established in 2007, Dr. Tabori leads the International Replication Repair Deficiency Consortium (IRRDC), a global initiative dedicated to understanding and managing genetic conditions and cancers caused by RRD. With over 200 clinicians and scientists collaborating from more than 50 countries, the IRRDC fosters innovation in precision oncology and translational research. The IRRDC is supported by a robust clinical and genomic database and biobank, which includes:

• 400+ unique tumor samples
• 600+ blood samples, along with cerebrospinal fluid, skin biopsies, and saliva from patients with RRD and their families
• 800+ registered patients with detailed clinical, treatment, and outcome data
• 4,000+ next-generation sequencing datasets, enabling comprehensive genomic analyses

This extensive resource facilitates cutting-edge research, beginning with understanding the fundamental biological processes and driving forces that contribute to cancer development. As a member of Dr. Tabori’s lab, you will have access to this extraordinary data and tissue repository, and opportunities to engage in advanced genomic studies, translational research, and collaborative projects with international experts in the field.

Recent Publications

1. Negm L, Chung J, Nobre L, et al. The landscape of primary mismatch repair deficient gliomas in children, adolescents, and young adults: a multi-cohort study. Lancet Oncol. 2025 Jan;26(1):123-135. PMID: 39701117

2. Ercan AB, Aronson M, Fernandez NR, et al. Clinical and biological landscape of constitutional mismatch-repair deficiency syndrome: an International Replication Repair Deficiency Consortium cohort study.Lancet Oncol. 2024 May;25(5):668-682. PMID: 38552658

3. Das A, Fernandez NR, Levine A, et al. Combined Immunotherapy Improves Outcome for Replication-Repair-Deficient (RRD) High-Grade Glioma Failing Anti-PD-1 Monotherapy: A Report from the International RRD Consortium. Cancer Discov. 2024 Feb 8;14(2):258-273. PMID: 37823831

4. Campbell BB, Galati MA, Stone SC, et al. Mutations in the RAS/MAPK Pathway Drive Replication Repair-Deficient Hypermutated Tumors and Confer Sensitivity to MEK Inhibition. Cancer Discov. 2021 Jun;11(6):1454-1467. PMID: 33563663

5. Chung J, Maruvka YE, Sudhaman S, et al. DNA Polymerase and Mismatch Repair Exert Distinct Microsatellite Instability Signatures in Normal and Malignant Human Cells. Cancer Discov. 2021 May;11(5):1176-1191. PMID: 33355208