# Identification of parasite erythrocyte membrane antigens specific to cerebral malaria and severe malarial anemia pathogenesis

> **NIH NIH F31** · UNIVERSITY OF MARYLAND BALTIMORE · 2021 · $16,410

## Abstract

PROJECT SUMMARY
Plasmodium falciparum is primarily responsible for severe malaria, including cerebral malaria and severe
malarial anemia. Malaria parasite variant surface antigens (VSAs) are parasite proteins displayed on the surface
of infected erythrocytes, facilitating cytoadhesion and sequestration by binding endothelial receptors in the host
vasculature. VSAs play a critical role in pathogenesis, and the expression of VSAs subclasses that bind specific
host receptors has been associated with severe malaria. However, the progression from mild to severe disease,
including to the particular severe disease syndrome, is not completely understood. Identifying which malaria
parasite proteins are important in the development of specific severe malarial syndromes will be crucial to
develop a vaccine against severe malarial disease. Plasmodium falciparum erythrocyte membrane protein-1
antigens (PfEMP1s) are the most well-characterized VSA family. The var gene family encodes PfEMP1s, with
an estimated 40-60 var genes per parasite genome. VSAs such as PfEMP1 bind to host endothelial receptors,
including intercellular adhesion molecule-1 (ICAM-1), CD36, and endothelial protein C receptor (EPCR), thereby
preventing immune clearance of infected erythrocytes. Identification of PfEMP1s at the protein level has been
hindered by the lack of sequence data to identify peptides specific to particular PfEMP1s in clinical infections.
RNA sequencing and subsequent proteomic profiling of the PfEMP1s on the surface of infected erythrocytes
from the same clinical infection enables an evaluation of expression at both the gene and protein level to identify
PfEMP1s specific to cerebral malaria and severe malarial anemia. Using samples from a case-control study in
Mali, West Africa that compared cases of severe malaria to matched controls with uncomplicated malaria, the
candidate will determine the association of the expression of PfEMP1s at the gene (Aim 1) and protein level (Aim
2). Identification of the PfEMP1s specific to severe malarial anemia and to cerebral malaria will shed light on the
pathogenesis of severe disease and inform studies to detect gaps in immunity to PfEMP1s identified from clinical
infections. This work will provide the candidate with valuable skills in the fields of transcriptomics, proteomics,
and bioinformatics that will prepare her for a career as a 21st century epidemiologist and independent academic
researcher.

## Key facts

- **NIH application ID:** 10484434
- **Project number:** 3F31HL147471-02S1
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Emily Marie Stucke
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $16,410
- **Award type:** 3
- **Project period:** 2019-06-07 → 2021-12-06

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10484434

## Citation

> US National Institutes of Health, RePORTER application 10484434, Identification of parasite erythrocyte membrane antigens specific to cerebral malaria and severe malarial anemia pathogenesis (3F31HL147471-02S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10484434. Licensed CC0.

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