I have dual training in basic science and medicine and a strong interest in the multifaceted clinical and scientific aspects of viral infection. I am currently investigating the diverse roles of NK cells in the setting of HIV infection on a Medical Research Council Clinician Scientist Fellowship. My group’s research goal is to optimise, direct, or specifically target NK cell subsets in therapeutic and preventative interventions that will allow us to overcome the current barriers to eliciting effective immunity to HIV.
One of my main areas of interest is the immunoregulatory role of NK cells. I have previously demonstrated that NK cells contribute towards the profound depletion of Hepatitis B Virus-specific T cells via a death receptor pathway, unveiling an important and novel mechanism of immune dysregulation. This was the first demonstration, in a human chronic viral infection, that NK cells can regulate the antiviral response in a negative fashion. During my current enquiry in HIV infection we aim to delineate the influence of genetic and environmental factors, such as CMV, on shaping NK cell function and any downstream effects on adaptive immunity. Our findings demonstrated that CMV coinfection/reactivation, a hallmark of HIV infection, plays an important role in driving a relative expansion of adaptive NK cells. More recently we identified a novel pathway involving the recycling endosome effector protein RAB11Fip5 that impacts adaptive NK cell functionality and development of HIV broadly neutralising antibodies. This work increased our understanding of NK cell regulation of humoral responses and has important implications for the development of new strategies to elicit a potent and durable neutralising antibody response by vaccination in HIV infection. My group also seeks to address metabolic changes in NK cell subsets and their impact on cellular function and associated immune activation and development of comorbidity in our aging HIV cohorts. We utilise a number of cellular immunology, virology and molecular techniques combined with cutting edge software platforms for the analysis of multiparameter data and we have expertise in Seahorse technology for assessment of cellular metabolism.
The clinical aspect of my work places me in an ideal environment to pose research questions with translational potential and bridge clinical and basic science work. I have created a research clinic at Mortimer Market Centre, London, encompassing one of the largest HIV cohorts in the country, to enable ongoing recruitment and blood sampling of eligible patients pre- and post-antiretroviral treatment to facilitate current and future research.
I have established key national and international collaborative links and maintain an interest in HBV infection and the role of CMV in driving comorbidity in our HIV infected cohorts.