This application is designed to address the molecular basis of malaria-associated anemia, one of the most prevalent and often life-threatening manifestations of infection with the malaria parasite. Hundreds of millions of people have clinical malaria infections every year and thus the impact of the disease on human health is profound. During the process by which the parasites invade erythrocytesto allow them to multiply within, parasite molecules bind to the surface of these cells. It is proposed that these molecules, which are also shed from the parasite, bind to uninfected erythrocytes in the infected host and promote the destruction and clearance of uninfected red blood cells, thus contributing to anemia. Furthermore it is proposed to test the hypothesis that specific antibodies to such molecules promote this clearance. Two molecular complexes consisting of abundant proteins that have been implicated in binding to host erythrocytes will be examined to define their structure, diversity and function. The components responsible for binding to red cells and their role in red blood cell invasion will be clarified. Their specific interactions with molecules of the erythrocyte membrane will be defined, and their pontential to exacerbate anemia examined in field-based studies. The properties of parasite lines in which specific genes, coding for components of one of these molecular complexes, have been deleted will be studied. The phenotype of these modified parasites may be expressed as a change of host cell specificity, or different growth rate, or in an alteration of the parasite- host balance. It is proposed that these genetically manipulated parasites can disturb the mechanisms that maintain the red cell equilibrium, leading to dysfunctional control of red cell numbers and consequent anemia. It will be important to establish whether molecules that are potential malaria vaccine candidates are also the targets of immune mechanisms that promote anemia.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
Project #
Application #
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Notre Dame
Notre Dame
United States
Zip Code
Safeukui, Innocent; Buffet, Pierre A; Deplaine, Guillaume et al. (2018) Sensing of red blood cells with decreased membrane deformability by the human spleen. Blood Adv 2:2581-2587
Safeukui, Innocent; Gomez, Noé D; Adelani, Aanuoluwa A et al. (2015) Malaria induces anemia through CD8+ T cell-dependent parasite clearance and erythrocyte removal in the spleen. MBio 6:
Mbengue, Alassane; Bhattacharjee, Souvik; Pandharkar, Trupti et al. (2015) A molecular mechanism of artemisinin resistance in Plasmodium falciparum malaria. Nature 520:683-7
Alam, Md Suhail; Getz, Michelle; Yi, Sue et al. (2014) Plasma signature of neurological disease in the monogenetic disorder Niemann-Pick Type C. J Biol Chem 289:8051-66
Fru-Cho, Jerome; Bumah, Violet V; Safeukui, Innocent et al. (2014) Molecular typing reveals substantial Plasmodium vivax infection in asymptomatic adults in a rural area of Cameroon. Malar J 13:170
Rey, Juliana; Buffet, Pierre A; Ciceron, Liliane et al. (2014) Reduced erythrocyte deformability associated with hypoargininemia during Plasmodium falciparum malaria. Sci Rep 4:3767
Jauréguiberry, Stéphane; Ndour, Papa A; Roussel, Camille et al. (2014) Postartesunate delayed hemolysis is a predictable event related to the lifesaving effect of artemisinins. Blood 124:167-75
Knuepfer, Ellen; Suleyman, Oniz; Dluzewski, Anton R et al. (2014) RON12, a novel Plasmodium-specific rhoptry neck protein important for parasite proliferation. Cell Microbiol 16:657-72
Heiber, Arlett; Kruse, Florian; Pick, Christian et al. (2013) Identification of new PNEPs indicates a substantial non-PEXEL exportome and underpins common features in Plasmodium falciparum protein export. PLoS Pathog 9:e1003546
Fernandez-Pol, Sebastian; Slouka, Zdenek; Bhattacharjee, Souvik et al. (2013) A bacterial phosphatase-like enzyme of the malaria parasite Plasmodium falciparum possesses tyrosine phosphatase activity and is implicated in the regulation of band 3 dynamics during parasite invasion. Eukaryot Cell 12:1179-91

Showing the most recent 10 out of 46 publications