Publications
Our Area of Focus
Since Dr. Tabori is a clinician-scientist, our research program is focused on combining biological and translational research in pediatric oncology. Most notably, we are interested in studying the mechanisms underlying brain tumor immortality and recurrence in the context of predisposition to cancer. Currently our group is studying three major areas related to this concept:
Replication Repair Deficiency
We have established the international consortium of Replication Repair Deficiency (IRRDC) which has uncovered clinical and biological implications of children with consitutional mismatch repair deficiency syndrome (CMMRD). We have uncovered that CMMRD cancers have the highest mutational load in humans and a mutation signature that can be traced to the germline. Our discovery of ultrahypermutation in CMMRD cancers has led to the first ever response to immune checkpoint inhibitors of recurrent glioblastoma (J Clin Oncol 2016) reported by the consortium and the implementation of two international clinical trials.
To learn more about the consortium and our RRD research, please visit the Replication Repair Deficiency Consortium website
Telomere Maintenance
Using a stepwise approach, we have explored the prognostic role of telomere maintenance in pediatric brain tumors. Initially, we showed that lack of telomere maintenance is involved in the unique property of spontaneous growth arrest seen in pediatric low grade gliomas and that telomerase is a significant biological risk factor in pediatric ependymomas . As a second step, we were able to demonstrate that telomerase, the enzyme which maintains telomeres, is active only in the tumor initiating cell (TIC) subpopulation of pediatric gliomas and telomerase inhibition causes growth arrest in glioma TIC cell lines. In contrast, normal stem cells lack telomerase and are insensitive to telomerase inhibition. Finally, we showed that telomerase inhibition results in irreversible loss of self-renewal capabilities of TIC in glioma and neuroblastoma in vitro and in vivo. Importantly, we have identified that a unique methylation of the hTERT promoter Tert Hypermethylated Oncological Region (THOR) is a cancer signature with immense clinical implications. This work resulted in a patent and commercialisation efforts by the Hospital for Sick Children and MaRS innovation in Toronto. We are currently exploring the causes of this phenomenon and the consequences of THOR in common adult cancers.
Click here to learn more about our Telomeres Maintenance research
Paediatric Low Grade Gliomas
Paediatric low grade gliomas (PLGG) are a clinical and translational passion of our group. PLGG is the most common childhood brain tumour 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. We have since initiated a multi-disciplinary Canadian 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 17 other paediatric cancer centres in Canada.
Click here to learn more about our Paediatric Low Grade Gliomas research
