My research passion lies with understanding what regulates the function of Natural Killer (NK) cells. NK cells constitute a heterogeneous population of innate lymphocytes that exhibit an extraordinary capacity to kill tumour cells and control certain viral infections. NK cells are able to act independently of specific antigen recognition making them a key constituent of the innate immune response. Their function is regulated by integrating a combination of activating and inhibitory signals received from ligands on their targets and my research questions focus on understanding how these signals regulate NK cell function.
My research projects include:
(1) Modulation of the NK Response by Human Cytomegalovirus
Human Cytomegalovirus (HCMV) is a ubiquitous β-herpes virus that establishes a persistent lifelong infection in the host. HCMV is a major cause of morbidity and mortality in immunocompromised individuals such as those suffering from HIV/AIDs or undergoing immunosuppressive drug therapies. The virus poses a significant risk to unborn foetuses and is a major cause of congenital malformation. NK cells play a crucial role in controlling cytomegalovirus infections such that individuals who are deficient in these cells often suffer from overt HCMV disease. My research focusses on identifying novel mechanisms encoded by the virus that enable it to modulate the NK cell response. This research gives us not only a better understanding of the interaction between NK cells and HCMV infected cells, but also has important implications for understanding the general mechanisms regulating NK cell function.
(2) Virotherapeutics and NK Cell function
NK cells have the ability to recognise and kill diverse types of tumour cells thus providing an attractive avenue for novel immunotherapeutic treatment of a range of cancers. However, in the clinic NK cell immunotherapy has been met with limited success and new approaches for harnessing the ability of NK cells to kill cancer cells are needed.
Oncolytic viruses, those that can selectively infect and kill cancer cells, offer a unique opportunity not only to directly kill cancer cells but to boost the immune response to eradicate tumours. Working in collaboration with Dr Alan Parker at Cardiff University, we are developing a novel oncolytic adenovirus vector that is capable of infecting primary ovarian cancer cells. This vector has the capacity to encode a transgene that when expressed can modulate the NK cell response. My research focusses on phenotyping and functionally profiling NK cells in the ascites of patients with ovarian carcinoma to better enable us to design a vector that can boost the natural ability of NK cells to recognise and lyse ovarian cancer cells in patients.