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 Molecular Pathogenesis and Biomarkers Section applies functional genomics and molecular immunoparasitology tools to understand malaria pathogenesis in naturally exposed individuals. Our goal is to identify malaria biomarkers and candidate vaccine antigens that may be useful in developing new interventions. Specifically, we focus on the following:
- Study malaria pathogenesis in naturally exposed children in Mali and Tanzania, including defining the adhesive properties of parasites associated with discrete clinical syndromes, and evaluate specific antibody responses that block parasite adhesion. This study is based on our model of pregnancy malaria. In this model, susceptibility to pregnancy malaria results from the unique binding profile of placental parasites that adhere to chondroitin sulfate A (CSA). Over successive pregnancies, women develop specific humoral immunity to placental parasites that are associated with reduced prevalence of infection, reduced parasite densities, and improved pregnancy outcomes.
- Identify and evaluate biomarkers for malaria disease and immunity that are urgently needed for vaccine development and monitor interventional trials using proteomic tools.
- Evaluate pregnancy malaria vaccine candidates.
- Identify parasite targets of pre-erythrocytic immunity to forward the development of a liver-stage vaccine using proteomic tools.
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.
Ben Orsburn, Scientist
Paul Southworth, Ph.D., Postdoctoral Fellow
Patricia Gonzales, Ph.D., Postdoctoral Fellow
Njinda Choo, Post-baccalaureate Fellow
Duffy PE, Fried M. Pregnancy malaria: cryptic disease, apparent solution. Mem Inst Oswaldo Cruz. 2011 Aug;106 Suppl 1:64-9.
Simpson DC, Kabyemela E, Muehlenbachs A, Ogata Y, Mutabingwa TK, Duffy PE, Fried M. Plasma levels of apolipoprotein A1 in malaria-exposed primigravidae are associated with severe anemia. PLoS One. 2010 Jan 21;5(1):e8822.
Fried M, Hixson KK, Anderson L, Ogata Y, Mutabingwa TK, Duffy PE. The distinct proteome of placental malaria parasites. Mol Biochem Parasitol. 2007 Sep;155(1):57-65.
Fried M, Domingo GJ, Gowda CD, Mutabingwa TK, Duffy PE. Plasmodium falciparum: chondroitin sulfate A is the major receptor for adhesion of parasitized erythrocytes in the placenta. Exp Parasitol. 2006 May;113(1):36-42.