Molecular Pathogenesis and Biomarkers Section
Established in 2011
Michal Fried, Ph.D.
Chief, Molecular Pathogenesis and Biomarkers Section
Major Areas of Research
- Biomarkers of malaria disease and immunity during pregnancy
- Malarial anemia pathways
- Targets of protective immunity in young children
The goal of the Molecular Pathogenesis and Biomarkers Section (MPBS) is to understand malaria disease pathogenesis and acquisition of immunity to malaria in pregnant women and young children. In seminal studies, Dr. Fried illuminated the immunopathogenesis of pregnancy malaria and described a model of protective immunity. In this model, pregnancy malaria results from the unique binding phenotype of placental parasites that adhere to chondroitin sulfate A (CSA); women acquire protective immunity in the form of functional anti-adhesion antibodies. MPBS has observed that malaria infection increases the risk of stillbirth and preterm delivery in primigravidae, and early neonatal death in multigravidae. Further, MPBS has demonstrated systemic inflammatory immune responses to malaria infection during pregnancy are associated with pregnancy loss and preterm delivery.
In malaria-endemic areas, severe malarial anemia is the major form of acute disease in young children. However, it is unclear why some children develop severe syndromes and others do not. MPBS has employed quantitative proteomics tools to identify interaction networks of proteins that significantly differ in abundance in children experiencing significant hemoglobin loss during malaria infection. Quantitative proteomics also identified multiple biomarkers that are currently being studied for their association with this pathology. Based on these results, future studies will be expanded to other severe malaria forms.
To study acquisition of protective immunity to malaria in young children, MPBS developed a proteomics pipeline to identify surface proteins expressed by parasites infecting young children. Using this approach, MPBS identified conserved and variant proteins (and protein complexes) associated with infected erythrocyte membranes, and related antibody levels in young children to such proteins with protection from disease. MPBS is now working to identify conserved PfEMP1 domains mediating parasite adhesion to the endothelium. These projects inform the ultimate goal to identify parasite proteins that elicit protective immunity and may be used as targets for vaccine development.
Dr. Fried earned her Ph.D. in molecular parasitology at Hebrew University (Israel) and M.Sc. in biochemistry at Ben-Gurion University (Israel). Her groundbreaking work elucidated the molecular basis of placental malaria and described the model of protective immunity that is the basis of current pregnancy malaria vaccine development. This model of pregnancy malaria is currently expanded to studies of severe malaria in children carried out in longitudinal studies in Africa.
- Key words: Malaria, pregnancy, childhood, Mali
- Key words: Pregnancy malaria, vaccine, in-vitro testing
- Key words: Malaria, pregnant women, Mali
Mahamar A, Gonzales Hurtado PA, Morrison R, Boone R, Attaher O, Diarra BS, Gaoussou S, Issiaka D, Dicko A, Duffy PE, Fried M. Plasma biomarkers of hemoglobin loss in Plasmodium falciparum-infected children identified by quantitative proteomics. Blood. 2022 Apr 14;139(15):2361-2376.
Mahamar A, Andemel N, Swihart B, Sidibe Y, Gaoussou S, Barry A, Traore M, Attaher O, Dembele AB, Diarra BS, Keita S, Dicko A, Duffy PE, Fried M. Malaria Infection Is Common and Associated With Perinatal Mortality and Preterm Delivery Despite Widespread Use of Chemoprevention in Mali: An Observational Study 2010 to 2014. Clin Infect Dis. 2021 Oct 20;73(8):1355-1361.
Araj BN, Swihart B, Morrison R, Gonzales Hurtado P, Teo A, Mahamar A, Attaher O, Diarra BS, Gaoussou S, Issiaka D, Dicko A, Duffy PE, Fried M. Antibody Levels to Plasmodium falciparum Erythrocyte Membrane Protein 1-DBLγ11 and DBLδ-1 Predict Reduction in Parasite Density. mSystems. 2021 Jun 29;6(3):e0034721.
Gonzales Hurtado PA, Morrison R, Ribeiro JMC, Magale H, Attaher O, Diarra BS, Mahamar A, Barry A, Dicko A, Duffy PE, Fried M. Proteomics Pipeline for Identifying Variant Proteins in Plasmodium falciparum Parasites Isolated from Children Presenting with Malaria. J Proteome Res. 2019 Nov 1;18(11):3831-3839.
Attaher O, Mahamar A, Swihart B, Barry A, Diarra BS, Kanoute MB, Dembele AB, Keita S, Gaoussou S, Issiaka D, Dicko A, Duffy PE, Fried M. Age-dependent increase in antibodies that inhibit Plasmodium falciparum adhesion to a subset of endothelial receptors. Malar J. 2019 Apr 11;18(1):128.
Fried M, Kurtis JD, Swihart B, Pond-Tor S, Barry A, Sidibe Y, Gaoussou S, Traore M, Keita S, Mahamar A, Attaher O, Dembele AB, Cisse KB, Diarra BS, Kanoute MB, Dicko A, Duffy PE. Systemic Inflammatory Response to Malaria During Pregnancy Is Associated With Pregnancy Loss and Preterm Delivery. Clin Infect Dis. 2017 Oct 30;65(10):1729-1735.
Patricia Gonzales, Ph.D., Staff Scientist
Raul Perez Caballero, Ph.D. (Visiting Fellow)
Bartholomew Nyangahu, Ph.D. (Postdoc IRTA)
Brittany Araj, Ph.D. (Postdoc IRTA)