Tumours of the central nervous system are a major cause of deaths resulting from cancer in children and adults. Gliomas account for almost 80% of primary malignant brain tumours. Gliomas are refractory to current modes of treatment primarily due to their invasive nature and their intrinsic resistance to radiation therapy and chemotherapy. One of the primary objectives of our studies therefore is to understand the basis of this intrinsic resistance to cell death by identifying regulators of apoptotic cell death of glioma cells.
Medulloblastoma is another malignant brain tumour that occurs commonly in children. Medulloblastoma is believed to be a result of deregulated nervous system development. However the pathogenesis of this tumour is largely unknown. Loss of chromosome 17p is the most common genetic alteration in medulloblastomas. Gene LLGL1 is one of the putative tumour suppressor genes from this region. Mutations in homolog of this gene in Drosophila gives rise to brain tumours. Sporadic human medulloblastomas tumour specimens are therefore being screened for possible genetic/epigenetic alterations in LLGL1 gene. We are also studying medulloblastomas from patched knock-out mice in order to understand the mechanism underlying tumourigenesis resulting from deregulated Hedgehog signaling.