Major Areas of Research
- Correlates of immunity: parasite adhesion phenotypes, parasite antigens, and antigen specific antibodies
- Disease biomarkers: pathways analysis of host response and disease comparison
- Identifying targets of pre-erythrocytic immunity
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. In non-immune women, MPBS observed that inflammatory immune responses in the placenta are associated with maternal anemia and low birthweight delivery. In collaboration with scientists in Mali, MPBS expanded pregnancy malaria epidemiology studies to relate malaria infection during pregnancy with risks for fetal loss and preterm delivery and relate inflammatory immune responses to placental malaria with fatal outcomes.
In malaria endemic areas, severe malarial anemia is the major form of severe disease in young children. However, it is not clear why some children develop severe syndromes and others do not. MPBS employed quantitative proteomics tools to identify interaction networks of proteins that significantly differ in abundance in plasma samples from children experiencing a significant reduction in hemoglobin during a malaria infection episode. Quantitative proteomics 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 proteomics pipeline to identify surface proteins expressed by parasites infecting young children. The ultimate objective is to identify parasite proteins that elicit protective immunity and may be used as targets for vaccine development. Using this approach, MPBS identified conserved and variant proteins associated with infected erythrocytes membranes that are currently under study, including relating antibody levels to in young children to surface proteins identified by proteomics with protection from disease, and identifying protein complexes associated with the membrane.
Dr. Fried earned her Ph.D. in molecular parasitology at Hebrew University (Israel) and M.Sc. in biochemistry at Ben-Gurion University (Israel). She made a groundbreaking work on the molecular basis of placental malaria and described the model of protective immunity that is the basis of the current effort to develop a pregnancy malaria vaccine. The model of pregnancy malaria is currently expanded to studies of severe malaria in children carried out in longitudinal studies in Africa.
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)
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;18(11):3831‐3839.
Mahamar A, Attaher O, Swihart B, Barry A, Diarra BS, Kanoute MB, Cisse KB, Dembele AB, Keita S, Gamain B, Gaoussou S, Issiaka D, Dicko A, Duffy PE, Fried M. Host factors that modify Plasmodium falciparum adhesion to endothelial receptors. Sci Rep. 2017;7(1):13872.
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;65(10):1729‐1735.
Attaher O, Mahamar A, Swihart B, Barry A, Diarra BS, Kanoute MB, Dembele AB, Keita S, Gaoussou S, Issiaka D, Dicko, Dufy PE, Fried M. Age-dependent increase in antibodies that inhibit Plasmodium falciparum adhesion to a subset of endothelial receptors. Malar J. 2019;18(1):128.
Andemel N, Gaoussou S, Barry A, Issiaka D, Mahamar A, Traore M, Duffy PE, Dicko A, Fried M. Adverse pregnancy outcomes among women presenting at antenatal clinics in Ouélessébougou, Mali. Reprod Health. 2020;17(1):39.