# Development of essential research tools for sustaining global programs for the elimination of human hookworms

> **NIH NIH R21** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2022 · $253,497

## Abstract

Hookworm genomes are currently poorly assembled and remain highly fragmented making it impossible to
determine changes in the genetic architecture in response to drug treatment, and thus to identify genes associated
with drug resistance. The long-term goal is to directly inform global health strategies for mitigating and addressing
drug resistance in soil-transmitted helminth (STH) parasites using both clinically applied and genetic/genomic
approaches. The overall objective of this application is to develop research tools for sustaining global programs for
the elimination of human hookworms as a public health problem. The rationale for this research is that developing
an optimal animal model and producing a highly contiguous genome assembly for hookworms will allow
identification of resistance loci and the development of new diagnostics to support and sustain global mass drug
administration programs (MDA). We propose two specific aims: 1) Develop a novel canine model to support
investigations into hookworm biology and genetics and 2) Produce a highly contiguous genome assembly for A.
caninum. In the first aim, a novel system for performing single-pair matings of A. caninum hookworms will be
developed whereby a pair of male/female immature worms will be placed in a gelatin capsule that will be deposited
in the mid-jejunum via endoscopic guided delivery. High levels of polymorphism in nematodes limit the contiguity
of genome assemblies, thus we will use this model to produce a new inbred line with reduced polymorphism. For
the second aim, inbred worms will serve as the source of genetic material for deep sequencing using long-read
sequencing together with short-read approaches to produce a highly contiguous genome assembly. The research
proposed in this application is innovative because we will develop an experimentally tractable and natural host
model with well-described physiology and biochemistry, making it an excellent translational model for human
hookworms. Furthermore, naturally evolved multiple-drug resistant isolates of A. caninum already exist and are
readily available, providing the source genetic material to interrogate the genetic loci involved with resistance.
Similar biologic resources and a model to exploit them for discovery do not currently exist for human hookworms.
The proposed research is significant because it is expected to provide essential resources and improve the
technical capability for studying the biology and genetics of drug resistance and other important traits in a largely
neglected, but medically relevant pathogen. Ultimately, the resources created in this research will facilitate future
investigations to develop the research and diagnostic tools necessary to support and sustain global programs for
the elimination of human hookworms as a public health problem. These outcomes are anticipated to have a positive
impact on the health and well-being of persons living in hookworm-endemic regions by improving the sustaina...

## Key facts

- **NIH application ID:** 10555769
- **Project number:** 7R21AI166281-02
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Rachel Fath Daniels
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $253,497
- **Award type:** 7
- **Project period:** 2022-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10555769

## Citation

> US National Institutes of Health, RePORTER application 10555769, Development of essential research tools for sustaining global programs for the elimination of human hookworms (7R21AI166281-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10555769. Licensed CC0.

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