# Elucidating host phosphosignaling regulation of Plasmodium vivax liver stage

> **NIH NIH R21** · SEATTLE CHILDREN'S HOSPITAL · 2021 · $213,780

## Abstract

ABSTRACT
Despite major eradication efforts over the past century, malaria remains a significant world-wide health burden.
Plasmodium vivax poses the greatest obstacle to malaria eradication due to its ability to form dormant stages
within the liver, called hypnozoites. Hypnozoites can reactivate weeks to years after the initial infection, leading
to relapses, and can only be targeted by two licensed drugs with extensive side effects and toxicity that limits
their use. Models of disease prevalence suggest that even a modest reduction of hypnozoite abundance in the
liver could make a major impact on the spread of disease. All Plasmodium parasites that have been
extensively studied have been shown to rely on specific host signaling events for invasion and development
through liver stage infection. These host factors represent potential targets for host-based interventions.
Unfortunately, there remains a dearth of knowledge regarding the host factors that permit Plasmodium vivax
liver stages to persist and develop, in large part because of technical challenges associated with growing the
parasite and then monitoring host signaling events in rare infected cells. Here, we propose to overcome these
challenges by using two approaches, kinase regression and digital spatial profiling, to interrogate host-driven
phosphosignaling in P. vivax-infected hepatocytes, including those that harbor hypnozoites. If successful, our
approach will identify host kinases that are necessary for P. vivax developing and dormant liver stages, as well
as phosphosignaling that is altered by infection. These data will dramatically enhance our understanding of
host factors that regulate Plasmodium vivax liver infection, and in doing so provide insight into the cellular
niche that promotes liver-stage parasite development and dormancy. In addition to enhancing the
understanding of this largely mysterious process, this information could inform host-directed therapies, which
represent a novel approach to targeting dormant malaria parasites.

## Key facts

- **NIH application ID:** 10170244
- **Project number:** 5R21AI151344-02
- **Recipient organization:** SEATTLE CHILDREN'S HOSPITAL
- **Principal Investigator:** Alexis Kaushansky
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $213,780
- **Award type:** 5
- **Project period:** 2020-05-22 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10170244

## Citation

> US National Institutes of Health, RePORTER application 10170244, Elucidating host phosphosignaling regulation of Plasmodium vivax liver stage (5R21AI151344-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10170244. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*