Research
Pathogenesis of parasitic infections: Mechanisms of cell invasion and survival during infection
The Carruthers lab seeks to understand invasion and survival strategies employed by microbial pathogens during infection. We use the protozoan Toxoplasma gondii as a model pathogen because of its genetic and biochemical tractability, well-defined cellular structure, and the availability of excellent rodent models of disease. Toxoplasma replicates in a remarkable variety of cells and organs, causing encephalitis, pneumonia, myocarditis, ocular disease, and congenital birth defects during acute infection. While disease is seen in only a small fraction of the ~2 billion people infected worldwide, the diagnosis and treatment of toxoplasmosis are suboptimal and the disease remains a significant and neglected public health problem. In people with healthy immune status, the parasite typically remains in a chronic, encysted state, but the infection can erupt when immune function is compromised such as individuals with HIV/AIDS, organ transplant recipients, or cancer patients undergoing chemotherapy.
Carrutherslab Predoc and Postdoc reunion 2022
As an obligate intracellular pathogen, Toxoplasma critically relies on cell invasion as a major survival strategy to avoid host antibody defense and phagocytic clearance. Cell invasion also initiates the parasite lytic cycle that ultimately destroys the infected cell, causing direct tissue pathology and indirect inflammatory damage. More >>
The team is also exposing the functions of parasite proteases including most notably a digestive enzyme termed cathepsin protease L. We showed that cathepsin protease L is the first marker of a novel and dynamic parasite digestive organelle we termed the vacuolar compartment or VAC. More >>
Our group is also keening interested in understanding mechanisms underlying parasite egress from host cells after replication therein. We have shown that a cytolytic protein (perforin-like protein 1) is crucial for efficient egress and is necessary for lethal infection in experimentally infected mice. More >>
We have established a mouse model of latent Toxoplasma infection to test new experimental compounds for efficacy in diminishing the chronic infection characterized by cysts within the CNS of the mice. More >>
Finally, our work is revealing new clues to the impact of latent T. gondii infection in the central nervous system. More >>
To navigate the above research avenues, we use a diverse array of approaches along the lines of molecular genetics, proteomics, biochemistry, pharmacology, cell biology, bioinformatics and structural biology. By addressing questions with multiple approaches yields we seek to obtain a robust understanding of Toxoplasma infection biology and disseminate the findings for conceptual integration into other infectious systems.