Uri Tabori

Section Head of Neuro-Oncology

Senior Scientist
Principal Investigator
Genetics & Genome Biology

U of T Positions

Professor (Full-Time) in the Department of Paediatrics & Medical Biophysics
Full Member of the Department of Medical Biophysics
Full Member of the Department of Medicine, Institute of Medical Science

Dr. Uri Tabori is the head of the Neuro-Oncology program at the Hospital for Sick Children and a Garron Family Chair appointment in Childhood Cancer Research. Dr Tabori is a Professor in the Departments of Medical Biophysics and Institute of Medical Science and Paediatrics, University of Toronto.

Based on his clinical background and expertise, his research focuses on translational aspects of cancer originating from patients need, through basic discoveries and clinical trials to changes in how society is managing specific cancers. Specifically, Dr Tabori focuses on the development of systems for early detection, intervention and therapeutics in children and young adults highly predisposed to developing brain tumors and the approach to low grade gliomas. 

Dr Tabori leads the international Replication Repair Deficiency consortium which is supporting patients and families in diagnosis, management and therapies in >50 countries. The consortium is running international clinical trials for children with hypermutant cancers with immune checkpoint inhibitors and combinations. Dr Tabori is also developing animal models and companion biomarker designed for immunotherapy therapeutics.

Dr Tabori also co-leads the pediatric low grade glioma taskforce which uncovers novel alterations in this most common brain tumor in children and offers targeted therapies and trials. He is responsible for the development of companion biomarkers to these trials.

Using these consortia, Dr Tabori and colleagues are focusing on using the immune system for cancer interception and prevention in children and young adults.

Dr. Tabori has been the recipient of numerous awards, including the Canadian Cancer Society’s Bernard and Francine Dorval Prize in and the Early Researcher Award from the Ontario Ministry of Development in Innovation. He has >300 peer reviewed publications and holds research grants from various international and national agencies the NIH, DOD, CIHR, Terry Fox, V-foundation, the Anti Cancer fund among others.

Research

My group has focused on combining biological and translational research in pediatric oncology. Specifically, we are interested in studying mechanisms underlying brain tumor immortality, recurrence and immune evasion in the context of predisposition to cancer. Currently our group is studying 2 major areas related to this concept:

Cancer predisposition syndromes

Germline predisposition to childhood brain tumors are a significant part of our research endeavors since I strongly believe that one can learn from germline alterations about somatic tumor events and from somatic tumor mutations on predisposition to cancer (Ying and yang of Cancer Genetics). Furthermore, these involve genomic instability, tumor immortality and are highly associated with telomere biology (see below). As a novel approach to cancer predisposition, we published a new method to predict tumor initiation in patients with germline mutations in TP53 (Cancer Res 2007, Cancer Res 2008). We then explored the Ying and Yang of cancer genetics in mutations in TP53 (germline: PNAS 2008, choroid plexus tumors J Clin Oncol 2010 and Clin Cancer Res 2014 and medulloblastoma: J Clin Oncol 2010, J Clin Oncol 2013).

In 2008, we have established theInternational Replication Repair Deficiency Consortium (IRRDC). In a stepwise approach, we have uncovered that RRD cancers have the highest mutation load in humans (Ultrahypermutant tumors, Nature Genet 2015, Cell 2017) and mutation signatures that can be traced to the germline (Cancer Discovery 2020, JCO 2022). The discovery of ultrahypermutation in RRD cancers resulted in the first ever response to immune checkpoint inhibitors of recurrent glioblastoma (JCO 2016, Nature Med 2022) reported by the consortium and implementation of 2 international clinical trials where the central laboratory is at Sickkids and supported by the consortium (Clin Cancer Res 2023). In parallel, we uncovered the role of early detection and surveillance in improved survival for RRD children and young adults (JCO 2022) and have uncovered the genomic and clinical landscape of these patients and cancers (Lancet Oncol 2024). Finally, we uncovered that replication repair deficiency is responsible for 5-10% of malignant gliomas in children and young adults and that diagnosis improves survival for these patients (Lancet Oncol 2025). We were then able to determine the genomic origins and stratify these gliomas to improve patient care (Nature Genet 2025).

The above findings are the basis of the new WHO book for childhood cancers and brain tumors as well as the AACR guidelines (CCR 2017 and 2024).

These highly collaborative research endeavors are ongoing and result in a wider understanding of main concepts in cancer and clinical targeted therapies for these children.

Current work of the consortium includes:

1. Determination of the tumor spectrum and risk stratification in individuals with
2. Establishment of diagnostic tools and molecular understanding of the events leading to the early and aggressive RRD
3. Validation and implementation of new non-invasive liquid biopsy surveillance tools for early cancer detection in
4. Determination of the genetic consequences of ultrahypermutation on the cancer genome and
5. Building animal models to study the syndrome and to uncover novel therapies to these cancers and specifically:
6. Development of drugs and vaccine approaches to prevent cancer initiation in
7. Development of clinical trials for RRD related

Importantly, an international clinical trial using immunotherapy for RRD cancers led by Sickkids and encompassing our global centers including low and middle income countries is planned to open this year and is funded by international and Canadian agencies to a total of >$3,000,000.

Pediatric low grade gliomas

Pediatric low grade gliomas (PLGG) are my clinical and translational passion. This is the most common childhood brain tumor and has unique biological characteristics ranging from spontaneous growth arrest to malignant transformation. We were the first to demonstrate the role of replicative senescence in PLGG and to utilize it as a prognostic factor for PLGG (Neoplasia, 2006). We then initiated and lead a multi- disciplinary international low grade glioma task force (PLGG taskforce) which incorporates clinical prospective trials, long term outcome studies and basic science questions. All of these are done in collaboration with the other pediatric cancer centers in Canada and worldwide under our

We currently have the largest PLGG clinical-pathological database in the world which includes more than 1000 patients and tumours. Furthermore, this clinical and biological repository is linked to >30 years of follow-up on these patients. We have utilized this Canadian effort in a series of >20 papers to demonstrate the following:

1. Clinical observations:
   1. defined the clinical and epidemiological role of PLGG located in the optic pathway, brainstem and spinal cord; each with its unique clinical outcome;
   2. defined the role of surgery, chemotherapy and radiation therapy in these tumors; specifically we have shown that radiation is not superior to other modalities and should be avoided if possible to these children;
   3. Demonstrated that second line chemotherapy is as efficacious as first line in this unique group of tumours; a fact that relates to oncogene induced
   4. Radiations Therapy result in risk of late deaths in adult survivors of PLGG (Cancer 2016).
2. With funding from OICR, we were able to construct two prospective trans-Canadian and international clinical trials for PLGG (JCO 2013, JCO 2016).
3. Together with Dr Nada Jabado from Montreal, we were one of the first to demonstrate that PLGGs possess the unique BRAF duplication (Brit Journal Cancer, 2008). We then extended our findings to demonstrate that this results in oncogene induced senescence and favorable outcome for these patients (Clin Cancer Res, 2011, Jacob et al Clin Cancer Res, 2011).
4. We have established the impact of BRAF V600E mutations in PLGG leading to the genetic events leading to transformation high grade gloma (J clin Oncol 2015) and response to targeted therapies (JCO PO 2021). Our data was key to the recently established role of these inhibitors in these cancers (NEJM 2023).
5. We have finalized the role of mutations in the RAS-MAPK in a landscape paper describing the drivers and their impact on outcome in PLGG (Cancer Cell 2020).
6. We established the Canadian Adolescents and young adults neurooncology network (CANON). This network which includes >30 centers in Canada and has centralized molecular pathology analysis, biweekly rounds and new clinical trials and approaches to these cancers. We recently summarized our data on 1000 patients 0-40 years old with glioma (Nature Cancer, under review).

Education and experience

• 1987–1993: MD, Hadassah School of Medicine, Hebrew University, Jerusalem, Israel.
• 1994–1995: Rotating Internship, Sorasky Medical Center, Tel-Aviv, Israel.
• 1995–1999: Residency, Department of Pediatrics, Sorasky Medical Center, Tel-Aviv, Israel.
• 1999–2002: Fellowship, Pediatric Hematology and Oncology. The Chaim Sheba Medical Center, Tel-Hashomer, Israel.
• 2002–2003: Staff, Pediatric Hematology and Oncology. The Chaim Sheba Medical Center, Tel-Hashomer and Sourasky Medical Center, Tel-Aviv, Israel.
• 2003–2006: Research and Clinical Fellowship. The Hospital for Sick Children, Toronto, Canada.

1. Shlien A, Campbell BB, de Borja R, et al. Combined Constitutional and Somatic Ablation of Replication Error Repair Results in Massive Mutation Load and Rapid Cancer Initiation. Nat Genet. 2015 Feb 2. SRA
2. Campbell BB, Light N, Fabrizio D, et al. Comprehensive Analysis of Hypermutation in Human Cancer. Cell. 2017 Nov 16;171(5):1042-1056.e10. doi: 10.1016/j.cell.2017.09.048. Epub 2017 Oct 19. SRA
3. Bouffet E, Larouche V, Campbell BB, et al. Immune Checkpoint Inhibition for Hypermutant Glioblastoma Multiforme Resulting From Germline Biallelic Mismatch Repair Deficiency. J Clin Oncol. 2016 Jul 1;34(19):2206-11. doi: 10.1200/JCO.2016.66.6552. SRA
4. Ryall S, Zapotocky M, Fukuoka K, Nobre L, et al. Integrated Molecular and Clinical Analysis of 1,000 Pediatric Low-Grade Gliomas. 2020 Apr 13;37(4):569-583.e5. doi: 10.1016/j.ccell.2020.03.011. Cancer Cell. 2020. Co-SRA
5. Castelo-Branco P, Choufani S, Mack S, Methylation of the TERT promoter and risk stratification of childhood brain tumours: an integrative genomic and molecular study. Lancet Oncology 2013 May; 14(6):534-42. SRA

See a full list of Dr. Tabori's publications on PubMed.