Overview of research by Heiko Wurdak

There are different types, subtypes and grades of brain cancer and to date, their origin, potential risk factors, and the factors underlying their growth are poorly understood.

Typical treatment strategies include surgery, chemo- and radiation therapy. However, the response of a tumour to a given therapy is often hard to predict. In particular, this is observed for aggressive, fast growing tumours such as Glioblastoma Multiforme, which is both the most common and lethal form of primary brain tumour.  Other brain tumours, for example low-grade gliomas, can convert to aggressive high-grade tumours over time, despite therapy. Unfortunately, the underlying bio-molecular causes are largely unclear and currently understudied. Clearly, a comprehensive research strategy that bridges between several disciplines (i.e. basic biology, medical research, radiation biology, therapeutic research, neuro-oncology, and neuro-surgery) is needed to gain the knowledge that can make a difference in terms of efficiently treating brain tumours in the future. 
 
Our neuro-oncology research team at Leeds is based at the St James’s University campus and we are part of the renowned University of Leeds School of Medicine committed to excellent research and teaching.

• Our team brings together expertise in basic and translational neuro-oncology and radiation biology - group of Professor Susan Short
  
• Brain tumour cell biology and stem cell biology - group of Dr Heiko Wurdak
  
• Brain tumour metastasis and tumour microenvironment - group of Dr Mihaela Lorger
  
• Targeted biological therapies - group of Professor Alan Melcher
  

Together, we work towards a better understanding of the biology of brain tumours that affect adults and children and we are particularly interested in how these tumours resist treatments including radiotherapy and chemotherapy and continue to grow. We look in detail at how tumour cells repair damage caused by radiation and chemotherapy drugs, how they may change their behaviour following treatment and how we may be able to use drugs or other bio-therapeutic agents to reverse the survival mechanisms that they use. Evolving technology in genomics research (a discipline in genetics studying the function and structure of many genes at the same time) allows us to look at brain tumour cells individually, so that we get information on them one by one, to help us understand how not all tumour cells are the same and why some grow despite treatment.
 
For example, a certain fraction of tumour cells has stem-cell like characteristics which have been linked to uncontrolled tumour growth and resistance to therapy. Other examples of tumour cells that currently cannot be efficiently targeted by conventional treatments are metastatic tumour cells reaching the brain (sometimes remaining inactive for years before growing brain tumour metastases) and low-grade tumour cells that turn into more aggressive tumour cells with stem cell-like features. We are investigating genes and proteins that make the above-mentioned cell types highly ‘dangerous’ and our ultimate goal is to develop treatments using either existing and/or novel experimental agents. Besides existing and novel experimental chemical compounds, we have started using anti-cancer (oncolytic) viruses for the treatment of aggressive brain tumours and brain tumor metastases. These viruses act both by directly killing cancer cells, and by stimulating an immune response against them. Moreover, we are exploring hematopoietic stem cells and their progeny as drug delivery vehicles in order to improve the delivery of therapeutic agents across the blood-brain barrier which strongly limits the access of drugs to the brain.
 
Overall, it is increasingly recognized that brain cancer is not a single disease but a very diverse array of different diseases, and therefore, the development ‘personalized’ treatments and combination therapies is urgently needed. Our aim is to contribute to these developments pursuing pre-clinical findings that are likely to translate into real benefits for patients, and towards this goal, we carry out early clinical trials. At the same time, using patient-derived cells and other suitable laboratory model systems in combination with state-of-the-art research technology, we aim to provide new insight into the complex biology of brain tumours.