Jayhun Lee

Developmental regulation of parasite survival and immune evasion by Schistosoma. Schistosomes are parasitic flatworms that cause schistosomiasis, a major parasitic disease that affects over 200 million people globally. After schistosomes infect a mammalian host through the skin, they are faced with epic existential challenges as they adapt to the new host environment: they must migrate into the bloodstream, begin to feed on blood, and absorb nutrients for development and reproduction, all while withstanding the host immune system. Failure of any of these events would disrupt the parasite's life cycle. We aim to discover the developmental mechanisms that endow schistosomes with such fascinating abilities to thrive inside the host. For example, we have recently discovered that a forkhead transcription factor, FoxA, directs schistosome stem cells to differentiate into the esophageal gland (EG), an anterior accessory organ of parasite's digestive tract, and is essential for the development and maintenance of the gland. Schistosomes lacking the gland are killed in immunocompetent mice but were able to survive in immunocompromised mice. Furthermore, EG-lacking parasites failed to lyse ingested immune cells within the esophagus before passing them into the gut, revealing a novel function of EG. Currently, we are taking a comparative transcriptomics approach followed by a large-scale functional screening to investigate the mechanism of EG-mediated parasite immune evasion. In parallel, we are taking functional genomics approach to discover other developmental regulators that play essential role in stem cell-driven differentiation, to investigate the function of major cell types/tissues (e.g., muscles and neurons) in parasite development and host-parasite interaction. During a tutorial rotation, students will explore how we maintain schistosome life cycle in the lab and learn modern molecular tools and methodologies of parasitology research including transcriptomic analysis, gene cloning, in situ hybridization, RNA interference, and high-resolution microscopy.