Helminthic Diseases – the Great Neglected Tropical Diseases
Helminths are parasitic worms. They are the most common infectious agents of humans in developing countries and produce a global burden of disease that exceeds better-known conditions, including malaria and tuberculosis. Insights into fundamental helminth biology are accumulating through newly completed genome projects and application of functional genomics technologies including germ line transgenesis and short hairpin RNA interference. At the same time, our understanding of the dynamics of the transmission of helminths and the mechanisms of the Th2-type immune responses, including inverse relationships with autoimmune and allergic diseases, which are induced by infection with these parasitic worms, is increasing.
Advances in molecular and medical helminth biology can be anticipated to translate into a new and robust pipeline of drugs, diagnostics, and vaccines to target parasitic worms that infect humans, to gain of deeper, fundamental understanding of these metazoan pathogens including their evolution and host parasite relationships, and to address other human maladies.
Infection Related Cancers
The NIH’s National Cancer Institute and the World Health Organization’s International Agency for Research on Cancer consider that ~20% of cancers are caused by infectious diseases. Some cancer-inducing infectious agents, such as Hepatitis B and C Viruses, are well known. However, less appreciated are the several major human helminth pathogens that cause cancer. These include the Schistosoma haematobium, the causative agent of urinary schistosomiasis and the fish borne liver flukes Opisthorchis viverrini and Clonorchis sinensis. In addition to direct detriment on development and health of infected populations, liver flukes and schistosomes, (types of helminth parasites collectively termed trematode flatworms), lead to infection related cancers, specifically liver and bladder cancer.
- Functional genomics technologies including genome, transcriptome and proteome analyses of schistosomes and liver flukes: innovative high throughput approaches to investigate ‘essentiality’ of parasite genes. Our research has pioneered deployment of mammalian retroviruses as gene transfer vectors for parasitic worms. The studies aim to identify intervention targets for development of novel anti-parasite interventions.
- Cohort and laboratory based studies in Opisthorchis viverrini liver fluke (fish borne pathogen) endemic regions in Thailand and adjacent countries to identify biomarkers of parasite associated bile duct cancer. Among other challenges, we are characterizing biomarkers of liver fluke induced liver with studies of non-coding RNAs including microRNAs and other macromolecules from infection related tumors. We are investigating bile and gut microbiomes of parasite infected individuals, and the genome and metabolites of this carcinogenic pathogen.
- Cohort and laboratory based studies in Schistosoma haematobium (blood fluke) endemic regions in Africa to identify biomarkers and understand the molecular pathogenesis of schistosome induced bladder cancer. Particular attention is focused on sterol like and other genotoxic metabolites from the parasite.