Tumour Virology

NON-COMMUNICABLE DISEASES / Cancer

Research Interests

Molecular biology of Human Papillomaviruses: virus entry pathways and induction of malignancy

Description of Research

Human Papillomaviruses (HPVs) are the causative agents of a number of human tumours, including cervical cancer, which is a major cause of cancer related death in women in many parts of the developing world. The development of HPV-induced malignancies requires the activity of two viral oncoproteins, E6 and E7. Together they act to deregulate a large number of cellular control pathways, primarily to create an environment favourable for viral replication, but which can ultimately give rise to malignancy. A major activity of the laboratory is to understand the molecular basis underlying the activities of E6 and E7 and how this contributes towards the development of cancer. Since E6 and E7 are essential for maintenance of the tumour phenotype, they also represent excellent candidates for therapeutic intervention in HPV-induced disease, and by characterising the functions of important cellular interacting partners, this can help identify novel therapeutic targets.  An important aspect of the laboratory’s work is the relevance that it has for understanding the mechanisms of cancer development in general, with many of the insights gained from studying the mechanisms of action of E6 and E7 being relevant for many other types of cancer.

The Tumour Virology Laboratory also has a strong interest in understanding how HPV enters the target cell. Current studies are focused on understanding how a viral capsid protein, L2, directs the incoming viral genome to the nucleus. In particular, we are interested in how this protein recruits the cellular machinery involved in the regulation of endocytic cargo transport, and thereby ensures the correct trafficking of the incoming viral genome. We are also interested in understanding how post-translational modification of the viral capsid proteins contributes towards virus entry, but also regulates virus assembly during a productive virus infection. These studies are intended to shed light on the fundamental aspects governing virus assembly and uptake, but may also provide information on novel means of therapeutic intervention.

The Group makes use of the latest molecular cell biology and biochemical techniques, focusing primarily on the cellular interacting partners of the viral proteins. As has been seen with many other DNA Tumour Virus models, HPV research offers unique insights into the processes affecting diverse and critical aspects of Cell Biology.

Recently, the Group has performed a genetic screen to identify IKK. as a target of HPV transformation (Barmchi, et al. Sci Reports 2021). Importantly, E6 interacts directly with IKK. and promotes the degradation of Magi. It is also significant that the reduction of IKK. inhibits the cooperative action of E6 and oncogenic RAS in transforming cells, and inhibitors of IKK. block the growth of cervical cancer cells, indicating that IKK. is a novel therapeutic target for treatment of HPV-dependent cervical cancer.

Recent Publications