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    Ann M Moormann PhD, MPH

    TitleAssociate Professor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentProgram in Molecular Medicine
    AddressUniversity of Massachusetts Medical School
    373 Plantation Street, Room 318
    Worcester MA 01605
    Phone508-856-8826
      Other Positions
      InstitutionUMMS - School of Medicine
      DepartmentPediatrics
      DivisionPediatric Immunology & Infectious Diseases

      InstitutionUMMS - School of Medicine
      DepartmentQuantitative Health Sciences
      DivisionEpidemiology of Chronic Diseases

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentClinical Population Health Research

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentImmunology and Virology

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentMasters in Clinical Investigation

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentMD/PhD Program

      InstitutionUMMS - Programs, Centers and Institutes
      DepartmentCenter for AIDS Research

        Overview 
        Narrative

        Research:

        Expertise

        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.



        Bibliographic 
        selected publications
        List All   |   Timeline
        1. Pinkevych M, Petravic J, Chelimo K, Vulule J, Kazura JW, Moormann AM, Davenport MP. Decreased Growth Rate of P. falciparum Blood Stage Parasitemia With Age in a Holoendemic Population. J Infect Dis. 2014 Apr; 209(7):1136-43.
          View in: PubMed
        2. Moormann A, Skiles J, Koros E, Asirwa FC, Busakhala N, Loehrer P. Mentoring future Kenyan oncology researchers. Infect Agent Cancer. 2013; 8(1):40.
          View in: PubMed
        3. Buckle GC, Collins JP, Sumba PO, Nakalema B, Omenah D, Stiffler K, Casper C, Otieno JA, Orem J, Moormann AM. Factors influencing time to diagnosis and initiation of treatment of endemic Burkitt Lymphoma among children in Uganda and western Kenya: a cross-sectional survey. Infect Agent Cancer. 2013; 8(1):36.
          View in: PubMed
        4. Wohlford EM, Asito AS, Chelimo K, Sumba PO, Baresel PC, Oot RA, Moormann AM, Rochford R. Identification of a novel variant of LMP-1 of EBV in patients with endemic Burkitt lymphoma in western Kenya. Infect Agent Cancer. 2013; 8(1):34.
          View in: PubMed
        5. Pinkevych M, Petravic J, Chelimo K, Vulule J, Kazura JW, Moormann AM, Davenport MP. Density-Dependent Blood Stage Plasmodium falciparum Suppresses Malaria Super-Infection in a Malaria Holoendemic Population. Am J Trop Med Hyg. 2013 Nov; 89(5):850-6.
          View in: PubMed
        6. Moormann AM, Sumba PO, Chelimo K, Fang H, Tisch DJ, Dent AE, John CC, Long CA, Vulule J, Kazura JW. Humoral and cellular immunity to Plasmodium falciparum merozoite surface protein 1 and protection from infection with blood-stage parasites. J Infect Dis. 2013 Jul; 208(1):149-58.
          View in: PubMed
        7. Mulama DH, Bailey JA, Foley J, Chelimo K, Ouma C, Jura WG, Otieno J, Vulule J, Moormann AM. 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. Int J Cancer. 2013 Feb 1; 134(3):645-53.
          View in: PubMed
        8. Chattopadhyay PK, Chelimo K, Embury PB, Mulama DH, Sumba PO, Gostick E, Ladell K, Brodie TM, Vulule J, Roederer M, Moormann AM, Price DA. Holoendemic malaria exposure is associated with altered Epstein-Barr virus-specific CD8(+) T-cell differentiation. J Virol. 2013 Feb; 87(3):1779-88.
          View in: PubMed
        9. Pinkevych M, Petravic J, Chelimo K, Kazura JW, Moormann AM, Davenport MP. The dynamics of naturally acquired immunity to Plasmodium falciparum infection. PLoS Comput Biol. 2012; 8(10):e1002729.
          View in: PubMed
        10. Dent AE, Moormann AM, Yohn CT, Kimmel RJ, Sumba PO, Vulule J, Long CA, Narum DL, Crabb BS, Kazura JW, Tisch DJ. Broadly reactive antibodies specific for Plasmodium falciparum MSP-1(19) are associated with the protection of naturally exposed children against infection. Malar J. 2012; 11:287.
          View in: PubMed
        11. Snider CJ, Cole SR, Chelimo K, Sumba PO, Macdonald PD, John CC, Meshnick SR, Moormann AM. Recurrent Plasmodium falciparum malaria infections in Kenyan children diminish T-cell immunity to Epstein Barr virus lytic but not latent antigens. PLoS One. 2012; 7(3):e31753.
          View in: PubMed
        12. Piriou E, Asito AS, Sumba PO, Fiore N, Middeldorp JM, Moormann AM, Ploutz-Snyder R, Rochford R. 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. J Infect Dis. 2012 Mar 15; 205(6):906-13.
          View in: PubMed
        13. McCarra MB, Ayodo G, Sumba PO, Kazura JW, Moormann AM, Narum DL, John CC. Antibodies to Plasmodium falciparum erythrocyte-binding antigen-175 are associated with protection from clinical malaria. Pediatr Infect Dis J. 2011 Dec; 30(12):1037-42.
          View in: PubMed
        14. Moormann AM, Snider CJ, Chelimo K. The company malaria keeps: how co-infection with Epstein-Barr virus leads to endemic Burkitt lymphoma. Curr Opin Infect Dis. 2011 Oct; 24(5):435-41.
          View in: PubMed
        15. Chelimo K, Embury PB, Sumba PO, Vulule J, Ofulla AV, Long C, Kazura JW, Moormann AM. Age-related differences in naturally acquired T cell memory to Plasmodium falciparum merozoite surface protein 1. PLoS One. 2011; 6(9):e24852.
          View in: PubMed
        16. Sutherland LJ, Cash AA, Huang YJ, Sang RC, Malhotra I, Moormann AM, King CL, Weaver SC, King CH, LaBeaud AD. Serologic evidence of arboviral infections among humans in Kenya. Am J Trop Med Hyg. 2011 Jul; 85(1):158-61.
          View in: PubMed
        17. Sumba PO, Kabiru EW, Namuyenga E, Fiore N, Otieno RO, Moormann AM, Orago AS, Rosenbaum PF, Rochford R. Microgeographic variations in Burkitt's lymphoma incidence correlate with differences in malnutrition, malaria and Epstein-Barr virus. Br J Cancer. 2010 Nov 23; 103(11):1736-41.
          View in: PubMed
        18. Spring MD, Chelimo K, Tisch DJ, Sumba PO, Rochford R, Long CA, Kazura JW, Moormann AM. 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. Infect Immun. 2010 Oct; 78(10):4431-41.
          View in: PubMed
        19. Asito AS, Piriou E, Odada PS, Fiore N, Middeldorp JM, Long C, Dutta S, Lanar DE, Jura WG, Ouma C, Otieno JA, Moormann AM, Rochford R. Elevated anti-Zta IgG levels and EBV viral load are associated with site of tumor presentation in endemic Burkitt's lymphoma patients: a case control study. Infect Agent Cancer. 2010; 5:13.
          View in: PubMed
        20. Moormann AM, Sumba PO, Tisch DJ, Embury P, King CH, Kazura JW, John CC. 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. Am J Trop Med Hyg. 2009 Sep; 81(3):489-95.
          View in: PubMed
        21. Dent AE, Chelimo K, Sumba PO, Spring MD, Crabb BS, Moormann AM, Tisch DJ, Kazura JW. Temporal stability of naturally acquired immunity to Merozoite Surface Protein-1 in Kenyan adults. Malar J. 2009; 8:162.
          View in: PubMed
        22. Piriou E, Kimmel R, Chelimo K, Middeldorp JM, Odada PS, Ploutz-Snyder R, Moormann AM, Rochford R. Serological evidence for long-term Epstein-Barr virus reactivation in children living in a holoendemic malaria region of Kenya. J Med Virol. 2009 Jun; 81(6):1088-93.
          View in: PubMed
        23. Moormann AM, Heller KN, Chelimo K, Embury P, Ploutz-Snyder R, Otieno JA, Oduor M, Münz C, Rochford R. Children with endemic Burkitt lymphoma are deficient in EBNA1-specific IFN-gamma T cell responses. Int J Cancer. 2009 Apr 1; 124(7):1721-6.
          View in: PubMed
        24. Moormann AM, Lozada JS. Burkitt lymphoma in Uganda: 50 years of ongoing discovery. Pediatr Blood Cancer. 2009 Apr; 52(4):433-4.
          View in: PubMed
        25. Greene JA, Moormann AM, Vulule J, Bockarie MJ, Zimmerman PA, Kazura JW. Toll-like receptor polymorphisms in malaria-endemic populations. Malar J. 2009; 8:50.
          View in: PubMed
        26. Asito AS, Moormann AM, Kiprotich C, Ng'ang'a ZW, Ploutz-Snyder R, Rochford R. Alterations on peripheral B cell subsets following an acute uncomplicated clinical malaria infection in children. Malar J. 2008; 7:238.
          View in: PubMed
        27. Dent AE, Bergmann-Leitner ES, Wilson DW, Tisch DJ, Kimmel R, Vulule J, Sumba PO, Beeson JG, Angov E, Moormann AM, Kazura JW. Antibody-mediated growth inhibition of Plasmodium falciparum: relationship to age and protection from parasitemia in Kenyan children and adults. PLoS One. 2008; 3(10):e3557.
          View in: PubMed
        28. Münz C, Moormann A. Immune escape by Epstein-Barr virus associated malignancies. Semin Cancer Biol. 2008 Dec; 18(6):381-7.
          View in: PubMed
        29. Noland GS, Hendel-Paterson B, Min XM, Moormann AM, Vulule JM, Narum DL, Lanar DE, Kazura JW, John CC. 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. Infect Immun. 2008 Dec; 76(12):5721-8.
          View in: PubMed
        30. Malhotra I, Wamachi AN, Mungai PL, Mzungu E, Koech D, Muchiri E, Moormann AM, King CL. Fine specificity of neonatal lymphocytes to an abundant malaria blood-stage antigen: epitope mapping of Plasmodium falciparum MSP1(33). J Immunol. 2008 Mar 1; 180(5):3383-90.
          View in: PubMed
        31. John CC, Tande AJ, Moormann AM, Sumba PO, Lanar DE, Min XM, Kazura JW. Antibodies to pre-erythrocytic Plasmodium falciparum antigens and risk of clinical malaria in Kenyan children. J Infect Dis. 2008 Feb 15; 197(4):519-26.
          View in: PubMed
        32. Rainey JJ, Rochford R, Sumba PO, Kowuor D, Wilson ML, Moormann AM. Family environment is associated with endemic Burkitt lymphoma: a population-based case-control study. Am J Trop Med Hyg. 2008 Feb; 78(2):338-43.
          View in: PubMed
        33. Dent AE, Yohn CT, Zimmerman PA, Vulule J, Kazura JW, Moormann AM. A polymerase chain reaction/ligase detection reaction fluorescent microsphere assay to determine Plasmodium falciparum MSP-119 haplotypes. Am J Trop Med Hyg. 2007 Aug; 77(2):250-5.
          View in: PubMed
        34. Rainey JJ, Mwanda WO, Wairiumu P, Moormann AM, Wilson ML, Rochford R. Spatial distribution of Burkitt's lymphoma in Kenya and association with malaria risk. Trop Med Int Health. 2007 Aug; 12(8):936-43.
          View in: PubMed
        35. Ostrout ND, McHugh MM, Tisch DJ, Moormann AM, Brusic V, Kazura JW. Long-term T cell memory to human leucocyte antigen-A2 supertype epitopes in humans vaccinated against smallpox. Clin Exp Immunol. 2007 Aug; 149(2):265-73.
          View in: PubMed
        36. Moormann AM, Chelimo K, Sumba PO, Tisch DJ, Rochford R, Kazura JW. Exposure to holoendemic malaria results in suppression of Epstein-Barr virus-specific T cell immunosurveillance in Kenyan children. J Infect Dis. 2007 Mar 15; 195(6):799-808.
          View in: PubMed
        37. Rainey JJ, Omenah D, Sumba PO, Moormann AM, Rochford R, Wilson ML. Spatial clustering of endemic Burkitt's lymphoma in high-risk regions of Kenya. Int J Cancer. 2007 Jan 1; 120(1):121-7.
          View in: PubMed
        38. Moormann AM, John CC, Sumba PO, Tisch D, Embury P, Kazura JW. 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. Am J Trop Med Hyg. 2006 Apr; 74(4):585-90.
          View in: PubMed
        39. John CC, McHugh MM, Moormann AM, Sumba PO, Ofulla AV. Low prevalence of Plasmodium falciparum infection among asymptomatic individuals in a highland area of Kenya. Trans R Soc Trop Med Hyg. 2005 Oct; 99(10):780-6.
          View in: PubMed
        40. John CC, Moormann AM, Pregibon DC, Sumba PO, McHugh MM, Narum DL, Lanar DE, Schluchter MD, Kazura JW. Correlation of high levels of antibodies to multiple pre-erythrocytic Plasmodium falciparum antigens and protection from infection. Am J Trop Med Hyg. 2005 Jul; 73(1):222-8.
          View in: PubMed
        41. Ofulla AV, Moormann AM, Embury PE, Kazura JW, Sumba PO, John CC. Age-related differences in the detection of Plasmodium falciparum infection by PCR and microscopy, in an area of Kenya with holo-endemic malaria. Ann Trop Med Parasitol. 2005 Jun; 99(4):431-5.
          View in: PubMed
        42. Moormann AM, Chelimo K, Sumba OP, Lutzke ML, Ploutz-Snyder R, Newton D, Kazura J, Rochford R. Exposure to holoendemic malaria results in elevated Epstein-Barr virus loads in children. J Infect Dis. 2005 Apr 15; 191(8):1233-8.
          View in: PubMed
        43. Rochford R, Cannon MJ, Moormann AM. Endemic Burkitt's lymphoma: a polymicrobial disease? Nat Rev Microbiol. 2005 Feb; 3(2):182-7.
          View in: PubMed
        44. John CC, Moormann AM, Sumba PO, Ofulla AV, Pregibon DC, Kazura JW. 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. Infect Immun. 2004 Sep; 72(9):5135-42.
          View in: PubMed
        45. Mwanda OW, Rochford R, Moormann AM, Macneil A, Whalen C, Wilson ML. Burkitt's lymphoma in Kenya: geographical, age, gender and ethnic distribution. East Afr Med J. 2004 Aug; (8 Suppl):S68-77.
          View in: PubMed
        46. John CC, O'Donnell RA, Sumba PO, Moormann AM, de Koning-Ward TF, King CL, Kazura JW, Crabb BS. 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. J Immunol. 2004 Jul 1; 173(1):666-72.
          View in: PubMed
        47. Cao K, Moormann AM, Lyke KE, Masaberg C, Sumba OP, Doumbo OK, Koech D, Lancaster A, Nelson M, Meyer D, Single R, Hartzman RJ, Plowe CV, Kazura J, Mann DL, Sztein MB, Thomson G, Fernández-Viña MA. Differentiation between African populations is evidenced by the diversity of alleles and haplotypes of HLA class I loci. Tissue Antigens. 2004 Apr; 63(4):293-325.
          View in: PubMed
        48. Moormann AM, Embury PE, Opondo J, Sumba OP, Ouma JH, Kazura JW, John CC. Frequencies of sickle cell trait and glucose-6-phosphate dehydrogenase deficiency differ in highland and nearby lowland malaria-endemic areas of Kenya. Trans R Soc Trop Med Hyg. 2003 Sep-Oct; 97(5):513-4.
          View in: PubMed
        49. Tkachuk AN, Moormann AM, Poore JA, Rochford RA, Chensue SW, Mwapasa V, Meshnick SR. Malaria enhances expression of CC chemokine receptor 5 on placental macrophages. J Infect Dis. 2001 Mar 15; 183(6):967-72.
          View in: PubMed
        50. Moormann AM, Sullivan AD, Rochford RA, Chensue SW, Bock PJ, Nyirenda T, Meshnick SR. Malaria and pregnancy: placental cytokine expression and its relationship to intrauterine growth retardation. J Infect Dis. 1999 Dec; 180(6):1987-93.
          View in: PubMed
        51. Moormann AM, Hossler PA, Meshnick SR. Deferoxamine effects on Plasmodium falciparum gene expression. Mol Biochem Parasitol. 1999 Jan 25; 98(2):279-83.
          View in: PubMed
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