Brain Cancer @ Leeds

Brain Cancer @ Leeds

We are a consortium of investigators from both basic research and clinical backgrounds, working to understand the processes that promote the development of different brain cancers, and translate our research findings for the benefit of brain cancer patients. Aggressive brain tumours have devastating outcomes for patients and their families. Through understanding their biology and establishing a clear route from laboratory to the clinic, we aim to contribute to more efficacious treatments for these diseases.

Breast cancer brain metastasis – Group Leader Dr Mihaela Lorger
Tumour microenvironment, including the immune cells, plays a critical role in tumour progression. Immune responses in the brain differ from immune responses elsewhere and therefore the brain is considered an “immune specialized” site. We aim to gain a better understanding of how the immune system works in the context of brain metastases and to exploit different immunomodulatory therapies. Main strategies are immune checkpoint inhibition and the delivery of immunomodulatory molecules within the progeny of hematopoietic stem cells that naturally home to brain tumours. We are also interested in mechanisms that lead to cancer cell dormancy in the brain. For more on the Brain Metastasis group see: http://www.braincancer.leeds.ac.uk/groups/brain-metastasis-group/

BrainMets

Intratumour heterogeneity and treatment resistance mechanisms in glioblastoma – Group Leader Dr Lucy Stead
Conventional therapies for the most deadly form of brain cancer, Glioblastoma (GBM), have limited efficacy: tumours regrow, even after aggressive treatment, killing more than half of all patients within one year of initial diagnosis. GBM is incurable because tumours are made up of distinct groups of cells with different characteristics that enable some of them to survive treatment. We are investigating GBM tumours in pairs (pre- and post-treatment) to learn how the abnormalities specific to certain groups of cells within the initial GBM allowed those cells to survive and enable the regrowth of an even less-treatable tumour. Once we know how and why those cells resisted treatment we can develop, or repurpose, drugs that specifically kill them. For more on the Glioma Genomics Group see: http://www.braincancer.leeds.ac.uk/groups/glioma-genomics/

BrainMets

Investigating mechanisms of radiation resistance – Group Leader Professor Susan Short
Malignant glioma patients are normally treated with radiotherapy to impede the progression of the disease. However, this only works partially, the tumours develop resistance and recurrence is inevitable. We are investigating mechanisms of radiation resistance in glioma and its association with the stem cell phenotype. We are researching novel ways of radio-sensitising tumours, particularly through inhibiting DNA repair. The main focus of this work falls into three areas:
i) Inhibiting homologous recombination
ii) Targeting stem cell maintenance pathways
iii) Promoting immunogenic cell death after radiation.

This lab work complements a portfolio of clinical studies for patients with glioma with a focus on novel adjuvant treatments for poor prognosis sub-types. For more on the Radiation Biology and Therapy Group see: http://www.braincancer.leeds.ac.uk/groups/radiationbiologyandtherapy/

Investigating molecular vulnerabilities and cellular plasticity in glioma – Group Leader Dr Heiko Wurdak
We have a passionate interest in identifying and characterizing molecular vulnerabilities in malignancies, in particular brain cancer. We use an interdisciplinary approach at the interface of stem cell and cancer biology, for example exploring the mechanisms of tumour progression with small molecules and chemical genetics (i.e., phenotype-to-target studies). Moreover, we investigate tumour cell plasticity and malignant self-renewal pathways through functional biology. To this end, we are developing and characterizing molecularly heterogeneous patient tumour models with the goal of making them accessible for research and drug discovery. Ultimately, we aim to contribute to the development of brain tumour precision medicine. For more on the Stem Cells and Brain Tumour Research Group see: http://www.braincancer.leeds.ac.uk/groups/stem-cells-and-brain-tumour-research-group/

Microenvironmental signalling and glioblastoma invasion – Group Leader Dr Georgia Mavria
A key hallmark of malignant gliomas is their invasive behaviour. Following treatment, tumours inevitably re-appear at least partly due to tumour cells having invaded the normal brain tissue at the time of resection. Another key feature, also used in diagnosis is the high degree of vascularity and counterintuitively, high levels of hypoxia. We are investigating signaling pathways that control glioblastoma invasion and activated in the aberrant microenvironment, and how blood vessel normalization can be achieved to improve the outcome of chemotherapy and radiotherapy. For more on the Signal Transduction and Tumour Microenvironment group see http://www.braincancer.leeds.ac.uk/groups/signal-transduction-and-tumour-microenvironment-group/

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