Research Interests

Kinetoplastid parasites comprise a diverse class of flagellated eukaryotic protozoa that diverged very early in the evolution of eukaryotes. This group includes three of the most important human protozoan pathogens: Trypanosoma cruzi, causative agent of American trypanosomiasis (Chagas disease); Trypanosoma brucei, which causes African trypanosomiasis (sleeping sickness); and species of the genus Leishmania which cause various clinical forms of leishmaniasis. As a result of sophisticated immune evasion strategies, kinetoplastids often cause long-term chronic infections. This can result in highly variable clinical outcomes between individual infected people, ranging from death and severe morbidity to milder forms and subclinical carrier states. The host, parasite and environmental factors that determine these heterogeneous outcomes are poorly understood. I aim to discover the mechanisms which determine host-parasite interaction dynamics during these infections and how these in turn shape tissue pathogenesis and organ dysfunction.

My main research focus is Trypanosoma cruzi biology and Chagas disease pathogenesis. There is a well-developed genetic engineering toolbox for T. cruzi, including bioluminescent:fluorescent fusion reporter genes and CRISPR-Cas9 systems for genome editing. This enables us to track the spatio-temporal dynamics of T. cruzi infections using in vitro, in vivo and ex vivo imaging models and to test hypotheses relating to parasite genetic factors by generating knockout, tagged and overexpression mutants. On the host side, we aim to use a variety of cutting-edge approaches to analyse immune responses, tissue damage and organ dysfunction, which can also be manipulated using genetic, chemical and immunomodulatory techniques. Integrating data on host, pathogen and pathology will help us to develop a more holistic understanding of the biological mechanisms involved in Chagas disease. We aim to use this knowledge to inform the development of more effective approaches to diagnosis and treatment.