Title: “Natural Product Drug Discovery for An Emerging Parasitic Nematode Disease”

Award Principal Investigator: Robert Nichols, PhD

Project Principal Investigators: Shugeng Cao, PhD, Robert Cowie, PhD, & William Gosnell, PhD

Award: $100,000 (as supplement to INBRE IV grant)

Project Summary: Rat lungworm (RLW) disease, or angiostrongyliasis, is caused by a parasitic roundworm, Angiostrongylus cantonensis that can be transferred to humans via snails or slugs. Ingestion of this nematode parasite can pathologically affect a person’s brain and spinal cord, possibly resulting in coma or death.

Unfortunately, there is no specific treatment for this neglected tropical disease. Natural products are an excellent source for anti-parasitic drug discovery, and our research team has established a natural product library mainly composed of under-explored Hawaiian endophytic fungi and other microorganisms.

We propose to screen our novel natural product library for new anti-RLW compounds through a collaborative initiative between INBRE and COBRE Investigators. The investigative team comprises a natural products chemist (Dr. Shegung Cao), a malacological parasitologist (Dr. Robert Cowie) and a medical parasitologist (Dr. William L. Gosnell). The unique natural products library will be screened to find compounds that will immobilize and kill infectious larvae of the RLW nematode that causes a devastating neuroinvasive disease of local significance, regional importance and global relevance, in the context of the globalization of food, recreational travel to RLW disease-endemic areas, and climate change.

We will carry out the following specific aims: 1) Test the efficacy of natural product compounds on infectious A. cantonensis larvae; and 2) Identify and characterize motility-inhibition bioactive natural product compounds through assay-guided separation and structure elucidation. This project will strengthen the UH research infrastructure in natural product drug discovery.

Also, this INBRE-COBRE collaboration will provide research experience opportunities in discovery science for undergraduate students at UH-Hilo and UH-Manoa to strengthen their pursuit of future careers in biomedical research.