# Investigating host kinase modulation of erythrocyte deformability during Plasmodium falciparum invasion

> **NIH NIH F31** · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · 2021 · $32,044

## Abstract

PROJECT SUMMARY/ABSTRACT
Malaria is a devastating disease caused by obligate intracellular Plasmodium parasites that infect millions of
people every year: In 2017 alone, 219 million people were infected by the parasite and 435,000 people were
killed. Every antimalarial deployed to date has been counteracted by cases of drug resistance, highlighting a
desperate need for novel drug targets.Targeting host factors is an underexplored alternative approach to
increasing barriers to drug resistance in malaria. This strategy has the potential to uncover targets required for
multiple Plasmodium species due to overlaps in host requirements. Additionally, many Plasmodium host factors
are already FDA approved drug targets, making a compelling case for drug repurposing.
 The red blood cell (RBC) is not a passive bystander during Plasmodium invasion; mounting evidence
suggests the RBC host is co-opted into modifying its own deformability during parasite attachment & invasion to
reduce the energy costs of parasite entry. These changes are driven by phosphorylation of the RBC cytoskeleton.
Host RBC kinases TRPM7, Casein Kinase II (CKII), and Syk are FDA approved drug targets postulated to
phosphorylate the RBC cytoskeleton during P. falciparum invasion. I hypothesize that Plasmodium signaling to
the RBC cytoskeleton during merozoite invasion occurs through these kinases to modulate RBC deformability
and facilitate parasite entry. My preliminary data indicates that P. falciparum invasion efficiency is compromised
in individual RBC knockouts targeting TRPM7, CSNK2A1, and SYK kinases.
 Using an integrated genetic, chemical genetic, and phosphoproteomics approach, this proposal seeks to
investigate TRPM7, CKII, and Syk kinase contributions to RBC deformation during P. falciparum invasion,
validate small molecule inhibitors targeting these kinases, and elucidate parasite stimuli and downstream
effectors mediating host kinase signal transduction during P. falciparum invasion. If successful, these studies
will uncover more about the basic biology of Plasmodium invasion, identify promising host targets for drug
repurposing in blood stage malaria, and facilitate the development of broad spectrum antimalarial compounds
with increased barriers to drug resistance. Finally, as many additional hematological disorders are affected by
these kinases—including macrothrombocytopenia & arterial fibrosis (TRPM7), hereditary spherocytosis &
Streptococcus-mediates hemolysis (Syk), and several hematological malignancies (CKII)—insights gleaned
from these functional analyses will benefit both parasitology and hematology communities.
 The proposed research will be carried out as part of my doctoral dissertation studies at the Harvard T.H.
Chan School of Public Health. During this fellowship I will acquire & strengthen technical skills including chemical
genetics, parasitology, and proteomics; and fine-tune data analysis, scientific communication, mentorship, and
professional development ...

## Key facts

- **NIH application ID:** 10431764
- **Project number:** 5F31HL154510-02
- **Recipient organization:** HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH
- **Principal Investigator:** Patrice Valerie Groomes
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $32,044
- **Award type:** 5
- **Project period:** 2020-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10431764

## Citation

> US National Institutes of Health, RePORTER application 10431764, Investigating host kinase modulation of erythrocyte deformability during Plasmodium falciparum invasion (5F31HL154510-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10431764. Licensed CC0.

---

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