Toxoplasma gondii is arguably one of the most successful protozoan parasites on the planet with nearly two billion people chronically infected. Infection by T. gondii is lifelong with potentially fatal toxoplasmosis occurring in developing infants and immunocompromised individuals. Although there are effective drugs to treat the acute phase of infection we currently have no way of treating the dormant cyst form of the parasite to stop individuals from suffering multiple rounds of reactivation.
T. gondii has served as an excellent model organism for the Apicomplexan family of parasites which include the more medically relevant Plasmodium (causative agent of malaria) and Cryptosporidium parasites (responsible for significant diarrheal disease in young children). Our research on Toxoplasma gondii touches on a variety of interesting topics related to host pathogen interactions including the continued study of known effectors, as well as the identification and characterization of new secreted proteins. We are also interested in how proteins destined for secretion are selected by the host sorting machinery and targeted to secretory organelles. We are also working to identify parasite proteins that are selectively secreted by the cyst forming bradyzoite stage that are critical to the formation of not only the cyst wall but also in modifying the host cell to tolerate long term parasitism by Toxoplasma gondii.
|Secreted Parasite Proteins
Using a variety of cutting edge techniques in molecular parasitology we have identified a panel of new hypothetical proteins that are secreted either into the host cell or into the parasite vacuole and are in the process of characterizing their function.
|Secreted Protein Trafficking Machinery
In our study of protein-protein interactions between parasite effectors and their host targets we have also identified parasite specific endogenous machinery involved in the selective trafficking of secreted effectors into secretory organelles and are interested in deciphering the molecular details of how they function.
|Bradyzoite Manipulation of the Host
We are currently interested in identifying the molecular machinery responsible for the generation of tissue cyst walls as well as the methods used by bradyzoites to manipulate their host cells to achieve long term parasitism.
|Trypanosoma cruzi is the causal agent of Chagas’ disease (American Trypanosomiasis) which infects nearly five million people in the Americas with another 70 million at risk of infection. It is one of the most severe parasitic disease currently plaguing the Americas. As with T. gondii, infection by T. cruzi is lifelong and chronic infection results in, among other things, severe cardiomyopathy in a third of infected individuals. T. cruzi remains grossly underreported, understudied and underfunded and this has resulted in a lack of fundamental tools to even accurately diagnose and treat this disease. Basic research on T. cruzi pathogenesis, up to now, has focused almost exclusively on the host immune response to infection due to a lack of efficient genetic tools to interrogate this parasite.
Fortunately for us, advances brought about by CRISPR/Cas9 genome editing technology have opened the door to performing detailed molecular studies of how T. cruzi effectively manipulates its host cell for the first time. We are implementing a variety of innovative techniques to identify, tag and knockout proteins secreted from this pathogen into the host cell that actively modify host cell processes to its advantage.