Dr. Pier Jr Morin, Assistant Professor of Biochemistry, University of Moncton, Moncton, New Brunswick
Project Title: “Understanding the Impact of tribbles proteins on glioblastoma development”
Malignant gliomas are the most common and deadly brain tumours. Nearly 2,600 cases of brain tumours were reported in Canada last year and the mean survival rate for a patient diagnosed with a glioblastoma multiforme, the most aggressive glioma, remained slightly over one year. Targeted therapies stemming from a better understanding of the molecular footprints characterizing these tumours have emerged as promising therapeutic approaches for the treatment of glioblastomas. The current proposal aims at characterizing one such footprint, a group of proteins showing increased levels in glioblastoma tumour samples, and at confirming then as bona fide Achilles heel underlying this type of tumour.
Differentially regulated protein kinases, key regulators of signal transduction, have garnered interest as druggable targets in glioblastomas. This project looks at two kinase targets that have been shown to be overexpressed in preliminary work; the tribbles proteins Trib1 and Trib2. While these proteins possess oncogenic properties in other cancer types, their precise role in glioblastomas is unclear. This proposal will look at the expression levels of these leads and undertake functional studies to assess their impact on glioblastoma progression thus setting the stage for the development of a tribbles-focused therapeutic approach in glioblastomas.
Improving our knowledge of the metabolic cascades associated with inherent and acquired temozolomide resistance in GBMs is, hence, of uttermost importance and was investigated as part of this research grant. Results collected within the current research program serve as a springboard to (1) develop a combinatorial therapeutic strategy directed towards these new targets and aimed at circumventing temozolomide resistance in GBMs and to (2) identify a signature of metabolites in temozolomide-resistant GBM patients that will pave the way for the development of an early detection test of patients not responding to temozolomide. In addition, it is important to mention that the financial help provided by Brain Tumour Foundation of Canada was instrumental in assisting a young investigator (Dr. Morin) in setting up a strong research environment in Eastern Canada and ensuring that this quickly translated to funding at the national level. This grant undoubtedly contributed to our objectives and the key results. Our understanding of the molecular footprint associated with GBMs has been greatly improved. Read more…