Rick M. Fairhurst, M.D., Ph.D.
Chief, Malaria Pathogenesis and Human Immunity Unit
Dr. Fairhurst received his M.D. and Ph.D. (molecular biology) degrees from the University of California, Los Angeles (UCLA). Following an internal medicine residency and an infectious diseases fellowship at UCLA Medical Center, he joined NIAID's Division of Intramural Research in 2001. A clinical tenure-track investigator, Dr. Fairhurst focuses his laboratory’s work on elucidating the mechanisms of malaria pathogenesis, human genetic resistance to malaria, acquired immunity to malaria, and parasite resistance to the artemisinin class of antimalarial drugs. He travels frequently to malaria-endemic areas of Mali and Cambodia, where his trainees and colleagues enroll patients into clinical research protocols and use patient and parasite specimens in laboratory experiments. Presently, Dr. Fairhurst serves as president of the American Committee on Molecular, Cellular, and Immunoparasitology (ACMCIP), a subcommittee of the American Society of Tropical Medicine and Hygiene (ASTMH). Recently, he was appointed deputy director of the NIH M.D.-Ph.D. Partnership Training Program. In 2011, Dr. Fairhurst received NIAID’s Outstanding Mentor of the Year Award.
Description of Research Program
Research in the Malaria Pathogenesis and Human Immunity Unit focuses on three goals:
- To improve our understanding of malaria pathogenesis
- To improve our understanding of host genetic resistance and acquired immunity to malaria in endemic areas
- To develop therapeutics and vaccines that reduce the morbidity and mortality of malaria
Major areas of investigation are centered on a newly proposed model for malaria protection (see Figure) and presently include the following:
- Mechanisms of malaria protection conferred by hemoglobin and red blood cell polymorphisms
- Mechanisms of host inflammation associated with the sequestration of parasitized red blood cells in host microvessels
- Identification of parasite virulence factors associated with severe disease outcomes
In each of these areas, we seek discoveries that improve knowledge of malaria pathogenesis and protection and thereby support searches for new antimalarial therapeutics and vaccines. Research activities in our unit are integrated with field studies in Africa and Southeast Asia.
Inquiries about pre-doctoral and postdoctoral fellowships, as well as Ph.D. studentships in the NIH Graduate Partnership Program, are welcome.
Genetic resistance and acquired immunity work together to confer protection against severe malaria
The sequestration of Plasmodium falciparum-infected red blood cells (RBCs) in microvessels is believed to activate microvascular endothelial cells (MVECs) and monocytes, which contribute to the inflammation associated with severe malaria. We recently identified a mechanism by which hemoglobin (Hb) C and sickle HbS may reduce the risk of severe disease. HbC and HbS are associated with abnormal display of P. falciparum erythrocyte membrane protein 1 (PfEMP1), a family of antigenically variant cytoadherence ligands that serves as the parasite’s main virulence factor on the surface of parasitized RBCs. Reduced levels and abnormal distributions of PfEMP1 are associated with impaired adherence of parasitized HbC and HbS RBCs to MVECs and monocytes. By lowering the avidity of adherence interactions, HbC and HbS may reduce the level of MVEC and monocyte activation in vivo and prevent the progression from uncomplicated to severe malaria. We propose that PfEMP1-specific IgGs also reduce the avidity of these interactions and thus work in concert with Hb variants to reduce inflammation and ameliorate disease severity. Our laboratory is working to strengthen and refine this model of malaria protection through in vitro experimental work and clinical research protocols in human populations of Mali and Cambodia, where the prevalence of variant hemoglobins is high.
To read more about Dr. Fairhurst’s global studies, read Fighting Drug-Resistant Malaria: Rick Fairhurst and Others at NIAID Go Global.
Research Group Members
Field Studies of Malaria Pathogenesis and Protection
In Mali, we currently have 1,500 children of all ages on a five-year longitudinal cohort study. In this study, we aim to improve our understanding of how hemoglobin C, hemoglobin S, alpha-thalassemia, and blood group O antigen protect against severe malaria. We are also working to identify novel host immune and genetic factors that control the progression from uncomplicated to severe malaria. In the first two years of this study, we diagnosed and treated nearly 2,000 episodes of malaria.
Malians at a table enrolling for a study
Malians enrolling for a study under a large tree
Enrollment of 1,500 children in Kenieroba, Mali (May 2008) Credit: NIAID
In Cambodia, we recently enrolled 1,100 individuals of all ages into a five-year longitudinal cohort study. In this study, we aim to improve our understanding of how hemoglobin E, alpha-thalassemia, G6PD deficiency, and blood group O antigen protect against severe P. falciparum malaria. We are also working to identify virulence determinants of P. vivax and host immune and genetic factors that control the progression from asymptomatic P. vivax parasitemia to symptomatic disease. In the first two years of our study, we diagnosed and treated nearly 700 episodes of malaria.
Cambodian village
Cambodian baby being immunized for malaria
Enrollment of 1,100 individuals in Thmar Da, Cambodia (April 2008) Credit: NIAID
Selected Recent Publications
To view a complete listing, visit PubMed.
Amaratunga C, Lopera-Mesa TM, Brittain NJ, Cholera R, Arie T, Fujioka H, Keefer JR, Fairhurst RM. A role for fetal hemoglobin and maternal immune IgG in infant resistance to Plasmodium falciparum malaria. PLoS One. 2011 Apr 12;6(4):e14798.
Fairhurst RM, Wellems TE. Plasmodium species, Malaria. In: Mandell GL, Bennett JE, Dolin R, editors. Principles and practice of infectious diseases. Philadelphia, PA: Elsevier; 2009. In press.
Cholera R, Brittain NJ, Gillrie MR, Lopera-Mesa TM, Diakité SA, Arie T, Krause MA, Guindo A, Tubman A, Fujioka H, Diallo DA, Doumbo OK, Ho M, Wellems TE, Fairhurst RM. Impaired cytoadherence of Plasmodium falciparum-infected erythrocytes containing sickle hemoglobin. Proc Natl Acad Sci USA. 2008 Jan 22;105(3):991-6.
Guindo A, Fairhurst RM, Doumbo OK, Wellems TE, Diallo DA. X-linked G6PD deficiency protects hemizygous males but not heterozygous females against severe malaria. PLoS Med. 2007 Mar;4(3):e66.
Fairhurst RM, Baruch DI, Brittain NJ, Ostera GR, Wallach JS, Hoang HL, Hayton K, Guindo A, Makobongo MO, Schwartz OM, Tounkara A, Doumbo OK, Diallo DA, Fujioka H, Ho M, Wellems TE. Abnormal PfEMP-1 display on erythrocytes carrying haemoglobin C may protect against malaria. Nature. 2005 Jun 23;435:1117-21.
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