Special Seminar: Mechanisms of tumorigenesis and therapeutic targets in brain tumors
Speaker: Jerome Fortin, Postdoctoral Fellow, Princess Margaret Cancer Centre, Toronto
Talk abstract: For most brain malignancies, current treatment options have limited effectiveness, resulting in poor prognosis. In diffuse gliomas, unique oncogenic lesions conspire to disrupt cellular epigenetics, metabolism, proliferation, differentiation, and the surrounding microenvironment. Crucially, the underlying molecular mechanisms, and how they may be effectively targeted by therapeutics, remain to be elucidated. To better understand how diffuse gliomas arise, progress, and could be treated, we generated and analyzed mouse and cellular models of specific disease subtypes. In pediatric diffuse midline gliomas (DMGs), we found that mutations in ACVR1 are sufficient to arrest cell differentiation, and can initiate tumorigenesis alongside cooperating genetic lesions. Prompted by these findings, we demonstrated the therapeutic potential of a kinase inhibitor that can simultaneously block two oncogenic pathways driving DMGs. In ongoing studies, we are employing functional genomics tools to identify candidate therapeutic synergies for DMGs. Furthermore, we are using a similar integrative strategy to investigate how IDH1-mutated adult diffuse gliomas are initiated and progress.
Bio: Jerome obtained is PhD from McGill University, working in the laboratory of Daniel Bernard in the Department of Pharmacology and Therapeutics. Jerome then moved to Toronto, where he joined the group of TakMak at the Princess Margaret Cancer Centre, as a postdoctoral fellow. In TakMak’s group, Jerome has been studying cancer biology, with a particular focus on brain tumors. Jerome has been using mouse models, functional genomics, and pharmacology, to study how diffuse gliomas develop and could be treated. Some of his work on pediatric diffuse midline gliomas was published in 2020 in Cancer Cell. Based on these studies, Jerome has received several awards and grant support, including a “Next Generation of Scientists” transition grant from the Cancer Research Society. Jerome is now interested in setting up a laboratory to pursue research on pediatric and adult brain tumors.