LMP student seminars: 7 January
Each week during term time, MSc and PhD candidates in the Department of Laboratory Medicine and Pathobiology present their research.
Anyone is welcome. No need to register.
Location: Medical Sciences Building, rooms 4171 or 4279, see below.
As part of the core research curriculum, students taking LMP1001/2/3: Graduate Seminars in Laboratory Medicine and Pathobiology will present their projects. Please see abstracts below.
Group 2: Cancer, Development and Aging
Location: MSB 4171
Lauren Omoto
- Title: Developing a “one-two punch” therapeutic paradigm for glioblastoma
- Supervisor: Dr. Phedias Diamandis
Group 1: Brain and Neuroscience
Location: MSB 4279
William Edward Bastedo
- Title: TBA
- Supervisor: TBA
Abstracts
Lauren Omoto: Developing a “one-two punch” therapeutic paradigm for glioblastoma
Glioblastoma (GBM) is the most prevalent and aggressive form of adult brain cancer, with median survival limited to 15-18 months despite treatment with the current standard-of-care therapies. One of the major barriers in the development of effective treatments is the ability of GBM cells to infiltrate into surrounding healthy brain tissue, evading current therapies and causing tumour recurrence. To address this, we are developing a “one-two punch” combination therapy. This paradigm involves the sequential administration of two compounds, the first to inhibit GBM cell invasion and induce cellular vulnerabilities, followed by a second compound that exploits these vulnerabilities to eliminate the cancer.
Utilizing a high-throughput spheroid invasion assay, we identified N,N-dimethyl sphingosine (DMS) as a potent inhibitor of GBM cell invasion, serving as a strong ‘first hit’ compound. The anti-invasive effects of DMS were recapitulated in glioma cerebral organoid (GLICO) and ex vivo organotypic mouse brain slice models of invasion.
Subsequent proteomic analysis of DMS-treated GBM cells was conducted to elucidate pathway shifts induced upon invasion inhibition. A high-throughput screen of tumour cells treated sequentially with both DMS and 892 different FDA-approved compounds was also conducted to identify potential synergistic combination therapies. The ability of the strongest combination treatments to induce GBM cell death will be validated using the aforementioned preclinical models.
By directly targeting the invasive phenotype of GBM cells with DMS in a combination treatment paradigm, we offer a novel approach to overcoming therapeutic resistance and improving patient outcomes.
William Edward Bastedo: TBA
TBA
Contact
No need to register.
Contact lmp.grad@utoronto.ca with any questions.