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Jose Stoute

TitleAssociate Professor
InstitutionCollege of Medicine
DepartmentMedicine
Address500 University Drive Hershey PA 17033
Phone7175318881

 Overview 
 overview
PREFERRED TITLE/ROLE:

Physician, Associate Professor of Medicine, and Microbiology and Immunology

GRADUATE PROGRAM AFFILIATIONS:

Microbiology and Immunology

EDUCATION:

Fellowship, Infectious Disease, Walter Reed Army Medical Center (District of Columbia) (1994)
Residency, Internal Medicine, Emory University School of Medicine (Georgia) (1988)
M.D., University of Miami School of Medicine (Florida) (1985)

NARRATIVE:

My laboratory focuses on the study of malaria, in particular Plasmodium falciparum. I have three areas of interest: pathogenesis, mechanisms of red cell invasion, and development of novel treatment strategies.

Malaria Pathogenesis:

P. falciparum malaria kills close to one million people per year. Most of these deaths occur in children in sub-Saharan Africa and are due to complications such as severe anemia and cerebral malaria. We do not have a complete understanding of the mechanisms that lead to these complications and we are also in need of better treatment strategies to decrease their mortality.

Severe Malarial Anemia (SMA):

Uninfected red cells are cleared from the circulation in greater numbers than infected red cells. The reasons for this are unknown. My laboratory has concentrated in understanding the role of complement and complement regulatory proteins in the destruction of uninfected red cells during P. falciparum malaria. We have documented that red cells from children with SMA have decreased complement receptor 1 (CR1/CD35) and decay accelerating factor (CD55/DAF). These two proteins act to protect red cells from complement activation. In addition, we have observed that these red cells have increased surface IgG and complement (C3) which can mark them for destruction when they interact with macrophages in the liver or spleen. We are currently developing a novel mouse model of SMA in which to test these ideas and develop novel strategies for treatment.

Cerebral Malaria (CM):

CM manifests itself as coma or seizures. It usually occurs in older children and adults. The pathognomonic lesion of CM in postmortem studies is sequestration of parasites in cerebral capillaries by adherence to endothelial cells. One school of thought is that this sequestration leads to decreased perfusion and CM. Ohters believe that local inflammation leading to production of cytokines and other inflammatory mediators can interfere with neurotransmitters. Other data from mice and human studies suggest that complement activation also plays a role here. Because there is a clear age differential predisposition to CM vs. SMA, we have concentrated in identifying differences in the expression of complement receptors on red cells. We have documented that CR1 and CD55 expression on red cells is high after birth and it dips to a nadir between 6-24 months and increases thereafter into adulthood. Therefore, it is possible that higher expression of complement receptors later in life places patients at risk. Data from other laboratories are supportive of this hypothesis. Our current work is concentrating on testing the role of complement and complement receptors using mouse knockouts in a model of cerebral malaria.

Mechanisms of Red Cell Invasion:

The mechanisms by which P. falciparum invades red cells are complex. The parasite has multiple ligands that can bind to a variety of red cell receptors. There is significant redundancy which is felt to be intended to evade the immune responses of the host. These factors have prevented the development of an effective vaccine that prevents red cell invasion. We recently demonstrated that the complement receptor 1 (CR1) is a red cell receptor of P. falciparum and is used for invasion. Our work is currently concentrated on understanding how this receptor is used and on identifying P. falciparum ligands that interact with it.

Development of Immunomodulators:

It is clear that effective immunomodulators are needed as adjunct therapy of SMA and CM, diseases in which the immune response of the host against the parasite is central to their pathogenesis. Children with SMA frequently required blood transfusions but in endemic countries they are seldom available when needed. Therefore, we need better ways to preserve the red cell mass in these children.

Novel Treatments:

With funding from the Gates Foundation, we are currently exploring the use of low power microwaves as potential treatment for malaria.


 Bibliographic 
 selected publications
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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  1. Liu X, Tao ZY, Fang Q, Wang XM, Zhang H, Stoute JA, Xia H, Cui L. A case of congenital plasmodium vivax malaria from a temperate region in Central China. Malar J. 2012; 11:182.
    View in: PubMed
  2. Odera M, Otieno W, Adhiambo C, Stoute JA. Dual role of erythrocyte complement receptor type 1 in immune complex-mediated macrophage stimulation: implications for the pathogenesis of Plasmodium falciparum malaria. Clin Exp Immunol. 2011 Nov; 166(2):201-7.
    View in: PubMed
  3. Stoute JA. Complement receptor 1 and malaria. Cell Microbiol. 2011 Oct; 13(10):1441-50.
    View in: PubMed
  4. Awandare GA, Spadafora C, Moch JK, Dutta S, Haynes JD, Stoute JA. Plasmodium falciparum field isolates use complement receptor 1 (CR1) as a receptor for invasion of erythrocytes. Mol Biochem Parasitol. 2011 May; 177(1):57-60.
    View in: PubMed
  5. Spadafora C, Awandare GA, Kopydlowski KM, Czege J, Moch JK, Finberg RW, Tsokos GC, Stoute JA. Complement receptor 1 is a sialic acid-independent erythrocyte receptor of Plasmodium falciparum. PLoS Pathog. 2010; 6(6):e1000968.
    View in: PubMed
  6. Ogonda LA, Orago AS, Otieno MF, Adhiambo C, Otieno W, Stoute JA. The levels of CD16/Fc gamma receptor IIIA on CD14+ CD16+ monocytes are higher in children with severe Plasmodium falciparum anemia than in children with cerebral or uncomplicated malaria. Infect Immun. 2010 May; 78(5):2173-81.
    View in: PubMed
  7. Odhiambo CO, Otieno W, Adhiambo C, Odera MM, Stoute JA. Increased deposition of C3b on red cells with low CR1 and CD55 in a malaria-endemic region of western Kenya: implications for the development of severe anemia. BMC Med. 2008; 6:23.
    View in: PubMed
  8. Mibei EK, Otieno WO, Orago AS, Stoute JA. Distinct pattern of class and subclass antibodies in immune complexes of children with cerebral malaria and severe malarial anaemia. Parasite Immunol. 2008 Jun-Jul; 30(6-7):334-41.
    View in: PubMed
  9. Bull PC, Buckee CO, Kyes S, Kortok MM, Thathy V, Guyah B, Stoute JA, Newbold CI, Marsh K. Plasmodium falciparum antigenic variation. Mapping mosaic var gene sequences onto a network of shared, highly polymorphic sequence blocks. Mol Microbiol. 2008 Jun; 68(6):1519-34.
    View in: PubMed
  10. Owuor BO, Odhiambo CO, Otieno WO, Adhiambo C, Makawiti DW, Stoute JA. Reduced immune complex binding capacity and increased complement susceptibility of red cells from children with severe malaria-associated anemia. Mol Med. 2008 Mar-Apr; 14(3-4):89-97.
    View in: PubMed
  11. Withers MR, McKinney D, Ogutu BR, Waitumbi JN, Milman JB, Apollo OJ, Allen OG, Tucker K, Soisson LA, Diggs C, Leach A, Wittes J, Dubovsky F, Stewart VA, Remich SA, Cohen J, Ballou WR, Holland CA, Lyon JA, Angov E, Stoute JA, Martin SK, Heppner DG. Safety and reactogenicity of an MSP-1 malaria vaccine candidate: a randomized phase Ib dose-escalation trial in Kenyan children. PLoS Clin Trials. 2006; 1(7):e32.
    View in: PubMed
  12. Ryan JR, Stoute JA, Amon J, Dunton RF, Mtalib R, Koros J, Owour B, Luckhart S, Wirtz RA, Barnwell JW, Rosenberg R. Evidence for transmission of Plasmodium vivax among a duffy antigen negative population in Western Kenya. Am J Trop Med Hyg. 2006 Oct; 75(4):575-81.
    View in: PubMed
  13. Stoute JA, Heppner DG, Mason CJ, Siangla J, Opollo MO, Kester KE, Vigneron L, Voss G, Walter MJ, Tornieporth N, Cohen JD, Ballou WR. Phase 1 safety and immunogenicity trial of malaria vaccine RTS,S/AS02A in adults in a hyperendemic region of western Kenya. Am J Trop Med Hyg. 2006 Jul; 75(1):166-70.
    View in: PubMed
  14. Stoute JA, Gombe J, Withers MR, Siangla J, McKinney D, Onyango M, Cummings JF, Milman J, Tucker K, Soisson L, Stewart VA, Lyon JA, Angov E, Leach A, Cohen J, Kester KE, Ockenhouse CF, Holland CA, Diggs CL, Wittes J, Heppner DG. Phase 1 randomized double-blind safety and immunogenicity trial of Plasmodium falciparum malaria merozoite surface protein FMP1 vaccine, adjuvanted with AS02A, in adults in western Kenya. Vaccine. 2007 Jan 2; 25(1):176-84.
    View in: PubMed
  15. Thathy V, Moulds JM, Guyah B, Otieno W, Stoute JA. Complement receptor 1 polymorphisms associated with resistance to severe malaria in Kenya. Malar J. 2005; 4:54.
    View in: PubMed
  16. Mibei EK, Orago AS, Stoute JA. Immune complex levels in children with severe Plasmodium falciparum malaria. Am J Trop Med Hyg. 2005 May; 72(5):593-9.
    View in: PubMed
  17. Stoute JA. Complement-regulatory proteins in severe malaria: too little or too much of a good thing? Trends Parasitol. 2005 May; 21(5):218-23.
    View in: PubMed
  18. Waitumbi JN, Donvito B, Kisserli A, Cohen JH, Stoute JA. Age-related changes in red blood cell complement regulatory proteins and susceptibility to severe malaria. J Infect Dis. 2004 Sep 15; 190(6):1183-91.
    View in: PubMed
  19. Ohas EA, Adams JH, Waitumbi JN, Orago AS, Barbosa A, Lanar DE, Stoute JA. Measurement of antibody levels against region II of the erythrocyte-binding antigen 175 of Plasmodium falciparum in an area of malaria holoendemicity in western Kenya. Infect Immun. 2004 Feb; 72(2):735-41.
    View in: PubMed
  20. Sun P, Schwenk R, White K, Stoute JA, Cohen J, Ballou WR, Voss G, Kester KE, Heppner DG, Krzych U. Protective immunity induced with malaria vaccine, RTS,S, is linked to Plasmodium falciparum circumsporozoite protein-specific CD4+ and CD8+ T cells producing IFN-gamma. J Immunol. 2003 Dec 15; 171(12):6961-7.
    View in: PubMed
  21. Stoute JA, Odindo AO, Owuor BO, Mibei EK, Opollo MO, Waitumbi JN. Loss of red blood cell-complement regulatory proteins and increased levels of circulating immune complexes are associated with severe malarial anemia. J Infect Dis. 2003 Feb 1; 187(3):522-5.
    View in: PubMed
  22. Schwenk R, Asher LV, Chalom I, Lanar D, Sun P, White K, Keil D, Kester KE, Stoute J, Heppner DG, Krzych U. Opsonization by antigen-specific antibodies as a mechanism of protective immunity induced by Plasmodium falciparum circumsporozoite protein-based vaccine. Parasite Immunol. 2003 Jan; 25(1):17-25.
    View in: PubMed
  23. Hoffman SL, Goh LM, Luke TC, Schneider I, Le TP, Doolan DL, Sacci J, de la Vega P, Dowler M, Paul C, Gordon DM, Stoute JA, Church LW, Sedegah M, Heppner DG, Ballou WR, Richie TL. Protection of humans against malaria by immunization with radiation-attenuated Plasmodium falciparum sporozoites. J Infect Dis. 2002 Apr 15; 185(8):1155-64.
    View in: PubMed
  24. Waitumbi JN, Opollo MO, Muga RO, Misore AO, Stoute JA. Red cell surface changes and erythrophagocytosis in children with severe plasmodium falciparum anemia. Blood. 2000 Feb 15; 95(4):1481-6.
    View in: PubMed
  25. Ballou WR, Kester KE, Stoute JA, Heppner DG. Malaria vaccines: triumphs or tribulations? Parassitologia. 1999 Sep; 41(1-3):403-8.
    View in: PubMed
  26. Stoute JA, Kester KE, Krzych U, Wellde BT, Hall T, White K, Glenn G, Ockenhouse CF, Garcon N, Schwenk R, Lanar DE, Sun P, Momin P, Wirtz RA, Golenda C, Slaoui M, Wortmann G, Holland C, Dowler M, Cohen J, Ballou WR. Long-term efficacy and immune responses following immunization with the RTS,S malaria vaccine. J Infect Dis. 1998 Oct; 178(4):1139-44.
    View in: PubMed
  27. Stoute JA, Ballou WR. The current status of malaria vaccines. BioDrugs. 1998 Aug; 10(2):123-36.
    View in: PubMed
  28. Ockenhouse CF, Sun PF, Lanar DE, Wellde BT, Hall BT, Kester K, Stoute JA, Magill A, Krzych U, Farley L, Wirtz RA, Sadoff JC, Kaslow DC, Kumar S, Church LW, Crutcher JM, Wizel B, Hoffman S, Lalvani A, Hill AV, Tine JA, Guito KP, de Taisne C, Anders R, Ballou WR, et al. Phase I/IIa safety, immunogenicity, and efficacy trial of NYVAC-Pf7, a pox-vectored, multiantigen, multistage vaccine candidate for Plasmodium falciparum malaria. J Infect Dis. 1998 Jun; 177(6):1664-73.
    View in: PubMed
  29. Stoute J, Ballou WR, Krzych U. Reply from stoute et Al. Parasitol Today. 1998 Feb; 14(2):83.
    View in: PubMed
  30. Stoute JA, Slaoui M, Heppner DG, Momin P, Kester KE, Desmons P, Wellde BT, Garçon N, Krzych U, Marchand M. A preliminary evaluation of a recombinant circumsporozoite protein vaccine against Plasmodium falciparum malaria. RTS,S Malaria Vaccine Evaluation Group. N Engl J Med. 1997 Jan 9; 336(2):86-91.
    View in: PubMed
  31. Stoute JA, Ballou WR, Kolodny N, Deal CD, Wirtz RA, Lindler LE. Induction of humoral immune response against Plasmodium falciparum sporozoites by immunization with a synthetic peptide mimotope whose sequence was derived from screening a filamentous phage epitope library. Infect Immun. 1995 Mar; 63(3):934-9.
    View in: PubMed
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