# Physiological roles of schistosome TRP ion channels with atypical pharmacology

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $402,500

## Abstract

Parasitic flatworms of the genus Schistosoma cause schistosomiasis, a tropical disease
affecting hundreds of millions of people worldwide. There is no vaccine, and only a single drug (praziquantel)
available for treatment and control. Many anthelmintics, likely including praziquantel, act on ion channels,
membrane protein complexes that are essential for normal functioning of the neuromusculature and other
tissues. However, few helminth ion channel families have been assessed for their properties and for their roles
in parasite physiology. One such overlooked group of helminth ion channels is the transient receptor potential
(TRP) channel superfamily. Members of the TRP channel family are widely diverse in their activation
mechanisms and ion selectivity, but share a common core structure. They are critical to transducing sensory
signals, responding to a wide range of external stimuli, and are also involved in other functions, such as
regulating intracellular calcium and organellar ion homeostasis and trafficking. TRP channels also respond to
endogenous agents, including those involved in inflammatory signaling. Our published and preliminary
pharmacological and knockdown studies show that schistosome TRP channels can be targeted to impact
normal neuromuscular and sensory function. More significantly, they appear to have novel pharmacological
sensitivities. Specifically, our results are consistent with the schistosome TRPA channel (SmTRPA) having at
least some of the pharmacological sensitivities of mammalian TRPV1 channels, particularly notable as there
are no TRPV channels represented in schistosome genomes. Preliminary functional expression studies
support this contention. We hypothesize that in schistosomes, SmTRPA fulfills some of the roles of missing
TRPV channels. We also hypothesize that SmTRPA and perhaps other schistosome TRP channels regulate
critical parasite-host interactions required for successful infection. This project will use parallel strategies to
define the roles SmTRPA and other TRP channels play in schistosome biology, including parasite-host
interactions, and assess SmTRPA channel function directly. Finally, we hypothesize that the schistosome TRP
channel, SmTRPML, plays key roles in schistosome endolysosomal physiology that can impact autophagy and
nutrient acquisition. Our studies will elucidate the biological roles and physiological properties of an almost
entirely unexplored family of parasite ion channels, information which could in the future be used to provide
novel candidate targets for new or repurposed antischistosomal agents. The specific aims of this project are to:
1) Determine the role that SmTRPA and other TRP channels play in the schistosome life cycle, including in
parasite-host interactions; 2) Use functional expression to test whether schistosome sensitivity to TRPV1
modulators is mediated specifically by SmTRPA; and 3) Elucidate the role of the schistosome TRPML channel
in endolysosomal functions, includi...

## Key facts

- **NIH application ID:** 9841879
- **Project number:** 5R01AI123173-04
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** ROBERT M GREENBERG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $402,500
- **Award type:** 5
- **Project period:** 2017-01-17 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9841879

## Citation

> US National Institutes of Health, RePORTER application 9841879, Physiological roles of schistosome TRP ion channels with atypical pharmacology (5R01AI123173-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9841879. Licensed CC0.

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