We study the protozoan parasite Cryptosporidium parvum, a leading cause of diarrhea in young children and neonatal calves. We use a combination of cutting-edge genetics, molecular and cellular biology approaches along with animal models of infection to uncover novel aspects of parasite biology.
The three main research focus areas in our laboratory are:
1. Unraveling signaling mechanisms that controls proliferation and development of Cryptosporidium
The Cryptosporidium parvum life cycle differs from other closely related apicomplexan parasites such as Plasmodium and Toxoplasma. This includes the dependency of Cryptosporidium to infect only intestinal epithelial cell, and the complexity to complete both the asexual and sexual stages in a single host. The successful completion of the life cycle requires a coordinated signaling program for the parasite to transition from one stage to another. However, the molecular signaling machinery that controls repeated re-infection of intestinal epithelial cells for asexual parasite proliferation, development of sexual stages, gamete fertilization and oocyst formation are not known. Our goal is to understand the molecular signaling mechanisms that control development of asexual and sexual stages for parasite proliferation and transmission. Unraveling these mechanisms will enhance our understanding of parasite biology and reveal new targets that can be targeted for vaccine and drug development against this deadly parasite.
2. Identifying and genetically validating new anti-cryptosporidial drug targets
There is no effective drug to treat cryptosporidiosis in children, immunocompromised individuals and animals. Thus, there is an urgent need to develop new drugs against Cryptosporidium. We seek to identify new compounds using high-throughput compound screening assay that utilize luciferase reporter expressing parasites, and evaluate the efficacy of compounds in vivo using mouse models of infection. Our goal is to ultimately understand the mechanism of action of potent compounds and to genetically validate their target in the parasite.
3. Developing new genetic tools to study parasite gene function
We have developed a conditional protein degradation system for Cryptosporidium. This system is allowing us to dissect the function of genes that are essential for parasite survival. We seek to further expand the molecular tool box for this parasite by devising new genetic approaches.