Leishmaniasis, a parasitic disease that causes symptoms ranging from disfiguring skin lesions to systemic disease and death, annually affects 1.6 million people. Current medications for leishmaniasis are toxic, expensive, and ineffective. This highlights the need to understand the underlying causes of disease severity. Parasites in the genus Leismania cause leishmaniasis, but the factors that lead a patient to develop a certain form of disease are poorly understood. For example, there is a strong association between particular Leishmania species and disease severity, but we do not understand how divergent evolution of parasite species led to this. My goal is to use evolutionary medicine to determine how the glycoprotein-63 (GP63) family of virulence factors behaves differently across Leishmania species and determine how these changes lead to specific types of leishmaniasis. As a protease, GP63 cleaves human proteins to exacerbate disease, but there is significant variation of GP63 within and between species that has not been studied. I will test whether these differences change the set of human proteins that GP63 cleaves and whether these changes influence the type of leishmaniasis that develops. This will improve our understanding of factors that influence the presentation and severity of leishmaniasis, and guide future studies to develop novel treatment strategies.
Antonia AL and Ko D (2020). Leishmaniasis: A spectrum of diseases shaped by evolutionary pressures across diverse life cycle. Evolution, Medicine, and Public Health 2020 (1): 139-140.
Antonia AL, Barnes AB, Martin AT, et al. (2021) Variation in Leishmani chemokine suppression driven by diversification of the GP63 virulence factor. PLoS Neglected Tropical Diseases 15(10): e0009224.