NEW YORK (GenomeWeb) — George Washington University School of Medicine and Health Sciences said this week that one of its research teams has been awarded a five-year, $1.7 million grant from the National Cancer Institute to study the molecular links between bile duct cancer and liver fluke infection.
The liver fluke is a parasitic worm that infects humans who consume raw or undercooked fish. It affects an estimated 10 million people in Southeast Asia alone. Notably, liver fluke infection is a key cause of bile duct cancer, although the mechanisms underlying this association are poorly understood.
GWU researcher Paul Brindley and collaborators at Thailand's Khon Kaen University have been using genomics to study liver flukes and identify biomarkers of bile duct cancer that is caused by the parasite. With the new funding from the NCI, the scientists aim to explore how proteins and extracellular vesicles excreted and secreted by the liver fluke lead to malignancy.
Specifically, the researchers will focus on the liver fluke growth mediator granulin Ov-GRN-1, as well as that parasite's extracellular vesicles (EVs) and their vesicle surface tetraspanins (TSP), which are known to enter biliary epithelial cells and induce proliferation, migration, angiogenesis, wound healing, and proinflammatory cytokine production, according to the grant's abstract.
Hypothesizing that blocking Ov-GRN-1 and EVs into bile duct epithelial cells will disrupt communication between the liver fluke and its host, Brindley and his team plan to use CRISPR-Cas9 genome editing to knock out the parasite's Ov-GRN-1 and TSP genes and evaluate the effects both in vitro and in a rodent model.
They will also study whether subunit Ov-GRN-1 and EV TSP vaccines can protect against liver fluke infection and infection-induced cancer, and address mechanisms by which functional antibodies minimize pathology, the abstract states.
"We're intrigued by and motivated to resolve the basic cellular question of how ... a worm [could] induce human tissue in the liver to become malignant," Brindley said in a statement. "It's a global public health problem — a neglected tropical disease that we would like to control."