Brain Tumour Research Laboratories
Professor Manuel Graeber moved to Sydney in January 2010 and is currently overseeing the laboratory development with his colleague, Dr Wei Li. The work of the Brain Tumour Research Laboratories will focus on the establishment of a new treatment for glioblastoma (GBM).
Gliomas are the most common brain tumours. GBM, a highly malignant variant, accounts for more than 20% of all primary brain tumours. Due to their highly diffuse infiltration of brain tissue, GBMs cannot be completely removed, and less than half of patients survive more than one year. It is the goal of our research program to develop a novel life-extending treatment for patients with these tumours.
We will combine experimental neuropathological and immunological techniques with some of the latest molecular genetic (zinc finger nucleases, ZFN) and cell culture (bioreactor) techniques in order to bring genetically enhanced microglia, the brain’s defence cells, into the tumour and its microenvironment. First, a syngeneic rat glioblastoma model will be established to determine the contribution of “bone-marrow derived microglia” (BMDM) to the population of tumour associated macrophages (TAMs). We will then make use of bioreactor technology for clinical scale ex vivo manufacture of microglia from hematopoietic progenitor cells (HPCs) and determine the utility of ZFN technology for the systematic genetic manipulation of both tumour cells and BMDM. The planned studies will provide comprehensive information on the origin and function of TAMs in malignant glioma. These studies aim to improve the understanding of BMDM and identify novel treatments of other CNS disorders, including common neurodegenerative conditions. Collectively, these studies are of broad relevance to the clinical neurosciences and should, beyond neuro-oncology, be of interest to oncologists who treat neoplasms outside the CNS that are characterised by the presence of TAMs.
The second project in the laboratories will investigate mechanisms of synaptic plasticity in the facial nucleus axotomy model, and this will also serve as a tissue control in our tumour experiments.