2017 Hellman Fellow
Assistant Professor, Molecular & Cell Biology, School of Natural Sciences
Project Title: Why vaccines fail
One sixth of the human population currently suffers from parasitic disease leading to an estimated 96 million disability-adjusted life years (DALYs) and 1 million deaths per year. With the exception of malaria, all major human parasitic diseases have been designated by the World Health Organization (WHO) as ‘neglected’ which often affect the poorest in third world and developing nations. In the last 20 years, only a handful of drugs have been developed for parasitic disease, and there have been major setbacks in vaccine development. A therapeutic or vaccine capable of activating the immune system to prevent parasitic disease will have a major impact on human health and the well-being of communities worldwide. However, there is only one partially protective vaccine in use for any human parasitic pathogen (RTS,S/AS01, 27% efficacy for malaria prevention).
Why is it so difficult to develop a protective vaccine for parasitic disease? Part of the answer lies with the ability of parasites to deflect, confuse, evade and antagonize the immune response as they seek out essential nutrients to sustain their growth and transmission between hosts. Parasites accomplish these feats through use of specialized virulence factors that manipulate cells and signaling pathways of the host it infects. In this project, we have identified how a widespread parasite of mammals and birds, Toxoplasma gondii, manipulates a critical cell of our immune system, called the CD8 T cell. It does so through the use of a novel virulence factor we have named ‘ROCTR’ (or ‘Regulator Of CD8 T cell Responses’). The Hellman fellowship is supporting our investigation into how T. gondii uses ROCTR to manipulate antigen presentation pathways required for activation of CD8 T cells. We think that by dissecting ROCTR’s function, important insights applicable to vaccine development for parasitic disease will be revealed.
“Thank you to the Hellman Fellowship for supporting early career investigators like myself. Your support is invaluable to us at a critical stage in our careers, and spurn innovation that will positively impact the world for years to come.”