Malaria Parasite Ligands And Host Cell Receptors

Miller, Louis

Abstract

Accomplishments during the year: 1. We continue the search for new receptors through genome-wide analysis of viable merozoites. 2. The immune response to AMA1, RON2 and EBA-175 has been studied. This work continues to expand our understanding of parasite invasion of red cells by identifying the receptors and ligands and determining the potential of these targets for vaccine development. 3. Study of epigenetics, using knockouts of P. falciparum genes involved in histone modification. 4. Antibodies to domains of PfEMP1 in severe disease in children in Africa. 5. Continue to study the cytoplasmic domains of molecules in the moving junction to determine if they bind to aldolase or other molecules that bind actin. Studying viable merozoites during invasion to follow the moving junction. 6. Elucidation of molecular mechanism of junction formation. 7. Plasmodium development in the mosquito.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Investigator-Initiated Intramural Research Projects (ZIA)
• Project #: 1ZIAAI000241-31
• Application #: 8555738
• Support Year: 31
• Fiscal Year: 2012
• Total Cost: $548,118

Institution

• Name: National Institute of Allergy and Infectious Diseases

Publications

Azasi, Yvonne; Lindergard, Gabriella; Ghumra, Ashfaq et al. (2018) Infected erythrocytes expressing DC13 PfEMP1 differ from recombinant proteins in EPCR-binding function. Proc Natl Acad Sci U S A 115:1063-1068

Bansal, Abhisheka; Molina-Cruz, Alvaro; Brzostowski, Joseph et al. (2018) PfCDPK1 is critical for malaria parasite gametogenesis and mosquito infection. Proc Natl Acad Sci U S A 115:774-779

Akkaya, Munir; Akkaya, Billur; Kim, Ann S et al. (2018) Toll-like receptor 9 antagonizes antibody affinity maturation. Nat Immunol 19:255-266

Arora, Gunjan; Hart, Geoffrey T; Manzella-Lapeira, Javier et al. (2018) NK cells inhibit Plasmodium falciparum growth in red blood cells via antibody-dependent cellular cytotoxicity. Elife 7:

Gunalan, Karthigayan; Niangaly, Amadou; Thera, Mahamadou A et al. (2018) Plasmodium vivax Infections of Duffy-Negative Erythrocytes: Historically Undetected or a Recent Adaptation? Trends Parasitol 34:420-429

Niangaly, Amadou; Karthigayan Gunalan; Amed Ouattara et al. (2017) Plasmodium vivax Infections over 3 Years in Duffy Blood Group Negative Malians in Bandiagara, Mali. Am J Trop Med Hyg 97:744-752

Miller, Louis H (2017) The Impact of Ken Warren's Leadership of the Rockefeller Foundation's Great Neglected Diseases Program on the Future of Malaria Research. Am J Trop Med Hyg 97:1958

Bansal, Abhisheka; Molina-Cruz, Alvaro; Brzostowski, Joseph et al. (2017) Plasmodium falciparum Calcium-Dependent Protein Kinase 2 Is Critical for Male Gametocyte Exflagellation but Not Essential for Asexual Proliferation. MBio 8:

Riggle, Brittany A; Miller, Louis H; Pierce, Susan K (2017) Do we know enough to find an adjunctive therapy for cerebral malaria in African children? F1000Res 6:2039

Sherling, Emma S; Knuepfer, Ellen; Brzostowski, Joseph A et al. (2017) The Plasmodium falciparum rhoptry protein RhopH3 plays essential roles in host cell invasion and nutrient uptake. Elife 6: