Department: Surgery, McMaster University
Dr. Singh’s lab applies a developmental neurobiology framework to the study of brain tumorigenesis. Building upon previously applied and refined cell culture techniques developed for the isolation of normal neural stem cells (NSC) to brain tumours, and development of a xenograft model to efficiently study brain tumour initiating cell (BTIC) activity, Dr. Singh’s lab aim to further define novel candidate cell surface markers to enrich for BTIC populations in human brain tumours. Using fluorescent activated cell sorting for multiple markers and conducting prospective isolation of different classes of brain tumour stem cells and gene expression profiling of tumour stem cells compared to their non-self-renewing neighbours, could potentially lead to the development of a molecular signature for each brain tumour subtype that will provide the platform to target new chemotherapies. Using her xenograft model coupled with either transgenic overexpressing BTICs or siRNA knockdown, Dr. Singh’s lab aims to respectively overexpress or underexpress key molecular mediators in the BTIC population permitting the functional characterization of signaling pathways that are disrupted during the possible transformation of the NSC to a BTIC. Capitalizing on approaches described in the aims above, Dr. Singh will apply rapid prospective purification of the BTIC, using a host of new potential BTIC markers, which may allow clinicians to pinpoint the transformed cell within a lineage hierarchy, and target it with appropriately tailored drug and molecular therapies. A functional analysis of BTICs from individual patients using in vitro clonogenic assays and in vivo transplantation assays may also provide a novel means for testing of new treatment strategies that focus on the eradication of the tumour-maintaining BTIC.