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Ann Moorman Faculty page

  • Immunology and Infectious Disease
  • Pediatrics
  • Epidemiology
  • Global Health Research

Research Interests:

Pediatric immunity to infectious diseases focusing on Plasmodium falciparum malaria and Epstein Barr Virus (EBV), molecular epidemiology, Global Health Research, and the etiology of endemic Burkitt lymphoma in Africa.

Professor Ann M. Moormann
is leading a study which aims to shed light on endemic Burkitt lymphoma. Here, she talks about her studies to date and her hopes for the future of her research: Understanding Endemic Burkitt Lymphoma

Description of Research Projects

Pediatric immunity and malaria
Understanding the development and maintenance of adaptive immunity to Plasmodium falciparum malaria in pediatric populations residing in African countries, where this parasitic infection is responsible for 1-2 million deaths each year, is the underlying them to the research conducted in my lab. Our studies of cellular and humoral immune responses to various malaria antigens from naturally infected humans help inform malaria vaccine design. Understanding the evolution of protective T cell memory to malaria also involves genotyping immunologically relevant malaria protein epitopes.

Malaria and EBV co-infections in the etiology of endemic Burkitt lymphoma
Endemic Burkitt lymphoma (eBL) is the most common pediatric cancer in sub-Saharan African and has been linked to early-age Epstein-Barr virus (EBV) infection and geographically to regions with high malaria transmission intensity (ie holoendemic malaria). Uncovering the etiologic mechanisms that explain how these pediatric co-infections lead to eBL is the another area of research in my laboratory.

Pediatric immunity to other infections and vaccine preventable diseases (ie measles)
Other co-infections of interest to our group include schistosomiasis, measles virus, and cytomegalovirus (CMV) due to either their immune-modulating potential or their ability to induce antigen-specific T cell immunity not associated with cancer that can serve as a positive control for our eBL studies. Such studies also provide a better understanding of fundamental aspects of T cell immunity in infants and young children.

Immunologic and viral predictors of survival for children with endemic Burkitt lymphoma
This project aims to establish non-invasive, readily measured correlates of long-term survival in pediatric patients diagnosed with endemic Burkitt lymphoma (eBL); that in turn can be used within the context of a future clinical trial aimed at improving the chemotherapeutic regimen used to cure this pediatric cancer. The kinetics and clinical usefulness of biomarkers such as EBV viral loads, the function and phenotype of EBV-specific T cell immunity and EBV serological profiles will be evaluated as diagnostic predictors within the context of our longitudinal study.

Rotation Projects

Potential rotation projects
My lab primarily investigates Plasmodium falciparum malaria-induced dysregulation of EBV-specific T cell immunity and its role in the etiology of endemic Burkitt lymphoma (eBL), the most prevalent pediatric cancer in Equatorial Africa. Within the context of our ongoing studies of healthy Kenyan children with divergent malaria exposure histories (chronic/repeated infections in a holoendemic area versus low infection rates in a nearby highland, malaria hypoendemic area) and by examining children diagnosed with eBL we have established a repository of samples that can be used to address this question.

1. One avenue of exploration involves homeostatic cytokine regulation of memory T cells. IL-15 and/or IL-7 responsiveness of EBV-specific memory T cells may be impaired in children with chronic malaria exposure and in children with endemic Burkitt lymphoma (eBL). We would like to investigate IL-15Ra and IL-7Ra surface expression, and CFSE proliferation of EBV-specific T cells in response to cognate antigen with and without IL-15 or IL-7 stimulation and compared children with divergent malaria exposure histories and children diagnosed with eBL. T cell responsiveness to IL-15 and IL-7 can be measured by STAT5 phosphorylation and the specificity of this effect for EBV-specific T cells can be evaluated by comparing IL-15Ra and IL-7Ra expression and responsiveness on other lymphocyte subsets and CMV-specific T cells.

2. Another putative mechanism by which malaria may interfere with the development of immunologic memory and influence EBV-specific T cell immunity is through the Programmed death-1 (PD-1) pathway. PD-1 is an immune inhibitory molecule that negatively regulates activated immune cells upon interacting with its ligands, programmed death ligand-1 (PD-L1) and programmed death ligand-2 (PD-L2) resulting in down-regulation of immune responses. Previous studies in murine and primate viral and parasitic diseases have reported the up-regulation of PD-1 and soluble PD-1 (sPD-1) but no studies have reported the expression of PD-1 in individuals from areas with divergent malaria transmission dynamics or in children presenting with endemic Burkitt lymphoma (eBL). In addition the PD-1 pathway has been suggested to be involved in the evasion of antitumor immunity by the host immune system. Preliminary studies in my lab suggest that PD-1 expression is significantly increased on CD4, CD8 T cells, B cells and NK cells in those residing in high malaria transmission areas compared to age-matched individuals without a history of malaria exposure. Future studies will explore the kinetics of this effect, the impact of antigen dose and how malaria exploits PD-1 mediated regulation to impair the development of immunologic memory.

3. Another area of interest is the role of Th17 cells in pediatric immunity. Because of the naturally delayed production of TH1 mediated pro-inflammatory cytokines (i.e. IL-12 and IFN-g) in utero, neonatal immunity is thought to be ‘suppressed’. However, more recent studies have shown that neonatal monocytes and antigen-presenting cells do express pro-inflammatory and regulatory cytokines (i.e. IL-6, IL-10 and IL-23) and at higher levels than adults. Thus TH17 cells appear to be an early, sequential response to pathogens prior to the induction of a TH1 or TH2 response. TH17 cells are also stimulated with IL-21 and IL-22 in an autocrine and paracrine fashion by natural killer cells. Exploring Th17 cell responses within the context of early-age human infections with malaria and EBV would be an exciting new avenue of investigation in my laboratory.

One or more keywords matched the following items that are connected to Moormann, Ann
Item TypeName
Academic Article Malaria enhances expression of CC chemokine receptor 5 on placental macrophages.
Academic Article Frequencies of sickle cell trait and glucose-6-phosphate dehydrogenase deficiency differ in highland and nearby lowland malaria-endemic areas of Kenya.
Academic Article Gamma interferon responses to Plasmodium falciparum liver-stage antigen 1 and thrombospondin-related adhesive protein and their relationship to age, transmission intensity, and protection against malaria.
Academic Article Endemic Burkitt's lymphoma: a polymicrobial disease?
Academic Article Malaria and pregnancy: placental cytokine expression and its relationship to intrauterine growth retardation.
Academic Article Age-related differences in the detection of Plasmodium falciparum infection by PCR and microscopy, in an area of Kenya with holo-endemic malaria.
Academic Article Stability of interferon-gamma and interleukin-10 responses to Plasmodium falciparum liver stage antigen-1 and thrombospondin-related adhesive protein in residents of a malaria holoendemic area.
Academic Article A polymerase chain reaction/ligase detection reaction fluorescent microsphere assay to determine Plasmodium falciparum MSP-119 haplotypes.
Academic Article Spatial distribution of Burkitt's lymphoma in Kenya and association with malaria risk.
Academic Article Serological evidence for long-term Epstein-Barr virus reactivation in children living in a holoendemic malaria region of Kenya.
Academic Article How might infant and paediatric immune responses influence malaria vaccine efficacy?
Academic Article Antibodies to Plasmodium falciparum erythrocyte-binding antigen-175 are associated with protection from clinical malaria.
Academic Article The dynamics of naturally acquired immunity to Plasmodium falciparum infection.
Academic Article Evidence that invasion-inhibitory antibodies specific for the 19-kDa fragment of merozoite surface protein-1 (MSP-1 19) can play a protective role against blood-stage Plasmodium falciparum infection in individuals in a malaria endemic area of Africa.
Academic Article Exposure to holoendemic malaria results in elevated Epstein-Barr virus loads in children.
Academic Article Correlation of high levels of antibodies to multiple pre-erythrocytic Plasmodium falciparum antigens and protection from infection.
Academic Article Exposure to holoendemic malaria results in suppression of Epstein-Barr virus-specific T cell immunosurveillance in Kenyan children.
Academic Article Antibodies to pre-erythrocytic Plasmodium falciparum antigens and risk of clinical malaria in Kenyan children.
Academic Article Fine specificity of neonatal lymphocytes to an abundant malaria blood-stage antigen: epitope mapping of Plasmodium falciparum MSP1(33).
Academic Article Low prevalence of antibodies to preerythrocytic but not blood-stage Plasmodium falciparum antigens in an area of unstable malaria transmission compared to prevalence in an area of stable malaria transmission.
Academic Article Antibody-mediated growth inhibition of Plasmodium falciparum: relationship to age and protection from parasitemia in Kenyan children and adults.
Academic Article Immune escape by Epstein-Barr virus associated malignancies.
Academic Article Alterations on peripheral B cell subsets following an acute uncomplicated clinical malaria infection in children.
Academic Article Toll-like receptor polymorphisms in malaria-endemic populations.
Academic Article Temporal stability of naturally acquired immunity to Merozoite Surface Protein-1 in Kenyan adults.
Academic Article Stability of interferon-gamma and interleukin-10 responses to Plasmodium falciparum liver stage antigen 1 and thrombospondin-related adhesive protein immunodominant epitopes in a highland population from Western Kenya.
Academic Article Allele specificity of gamma interferon responses to the carboxyl-terminal region of Plasmodium falciparum merozoite surface protein 1 by Kenyan adults with naturally acquired immunity to malaria.
Academic Article Microgeographic variations in Burkitt's lymphoma incidence correlate with differences in malnutrition, malaria and Epstein-Barr virus.
Academic Article The company malaria keeps: how co-infection with Epstein-Barr virus leads to endemic Burkitt lymphoma.
Academic Article Early age at time of primary Epstein-Barr virus infection results in poorly controlled viral infection in infants from Western Kenya: clues to the etiology of endemic Burkitt lymphoma.
Academic Article Recurrent Plasmodium falciparum malaria infections in Kenyan children diminish T-cell immunity to Epstein Barr virus lytic but not latent antigens.
Academic Article Broadly reactive antibodies specific for Plasmodium falciparum MSP-1(19) are associated with the protection of naturally exposed children against infection.
Academic Article Holoendemic malaria exposure is associated with altered Epstein-Barr virus-specific CD8(+) T-cell differentiation.
Academic Article Humoral and cellular immunity to Plasmodium falciparum merozoite surface protein 1 and protection from infection with blood-stage parasites.
Concept Malaria
Concept Malaria Vaccines
Concept Malaria, Falciparum
Academic Article Sickle cell trait is not associated with endemic Burkitt lymphoma: an ethnicity and malaria endemicity-matched case-control study suggests factors controlling EBV may serve as a predictive biomarker for this pediatric cancer.
Academic Article Density-dependent blood stage Plasmodium falciparum suppresses malaria super-infection in a malaria holoendemic population.
Academic Article Decreased growth rate of P. falciparum blood stage parasitemia with age in a holoendemic population.
Academic Article Effect of transmission intensity and age on subclass antibody responses to Plasmodium falciparum pre-erythrocytic and blood-stage antigens.
Academic Article Absence of putative artemisinin resistance mutations among Plasmodium falciparum in Sub-Saharan Africa: a molecular epidemiologic study.
Academic Article The hunt for protective correlates of immunity to Plasmodium falciparum malaria.
Academic Article Time-to-infection by Plasmodium falciparum is largely determined by random factors.
Academic Article Plasmodium falciparum Protein Microarray Antibody Profiles Correlate With Protection From Symptomatic Malaria in Kenya.
Academic Article Impact of Plasmodium falciparum Coinfection on Longitudinal Epstein-Barr Virus Kinetics in Kenyan Children.
Academic Article Longevity of Genotype-Specific Immune Responses to Plasmodium falciparum Merozoite Surface Protein 1 in Kenyan Children from Regions of Different Malaria Transmission Intensity.
Academic Article Malaria - how this parasitic infection aids and abets EBV-associated Burkitt lymphomagenesis.
Academic Article Does EBV alter the pathogenesis of malaria?
Academic Article Modeling of EBV Infection and Antibody Responses in Kenyan Infants With Different Levels of Malaria Exposure Shows Maternal Antibody Decay is a Major Determinant of Early EBV Infection.
Academic Article Regulatory T Cells in Endemic Burkitt Lymphoma Patients Are Associated with Poor Outcomes: A Prospective, Longitudinal Study.
Academic Article New gorilla adenovirus vaccine vectors induce potent immune responses and protection in a mouse malaria model.
Academic Article Immune effector mechanisms in malaria: An update focusing on human immunity.
Academic Article Endemic Burkitt lymphoma - an aggressive childhood cancer linked to Plasmodium falciparum exposure, but not to exposure to other malaria parasites.
Academic Article Pediatric Participant Retention Rates in a Longitudinal Malaria Immunology Study.
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  • Malaria