Dr Gemma Kelly
The Walter and Eliza Hall Institute of Medical Research
The Epstein-Barr virus (EBV) is associated with a number of human cancers. In one such cancer called Burkitt Lymphoma, we found that the virus can express a protein called BHRF1.
BHRF1 is a viral homologue of the cellular protein BCL-2 that protects cells from dying. Our data indicates tumours that express BHRF1 would be difficult to kill with conventional chemotherapy. We want to examine the role of BHRF1 in the initiation and growth of lymphoma cells and to understand how BHRF1 interacts with the host cell proteins to keep lymphoma cells alive and make them resistant to chemotherapeutic drugs.
What is the need?
EBV is known to be associated with several different human cancers, including lymphomas and carcinomas, contributing to 200,000 cancers annually worldwide. More than 90% of the human population are infected with EBV but only in some individuals will EBV ultminately cause cancer. We still do not fully understand how the virus causes cancer, particularly in the case of lymphomas in which only a limited number of viral proteins are expressed.
The long-term goal of this project is to design a drug against BHRF1 that could be used to treat patients with aggressive lymphoma.
What impact will this research have?
This research will provide a clear understanding of how BHRF1 interacts with cellular proteins to keep cells alive, thereby contributing to cancer initiation and the resistance to conventional chemotherapy. A clear understanding of how BHRF1 works is key to the future design of drugs that can bid to BHF1 and inhibit its function. Furthermore, there are a growing number of human cancers known to be associated with viruses and we anticipate that our research will shed new light on this.
The development of viral vectors we can use to express mutant forms of BHRF1 in lymphoma cells in the lab.
Identify regions of BHRF1 that are necessary for it to function to protect cells from death and to accelerate lymphoma development.
|Use novel genome editing techniques to remove BHRF1 from lymphoma cells and assess the effect on tumour cell growth.
"The long-term goal of this project is to design a drug against BHRF1 that could be used to treat patients with aggressive lymphoma."