Research and Professional Experience
Dr. Scorpio’s research focuses on the pathogen Anaplasma phagocytophilum, an obligate intracellular rickettsial organism that survives in host neutrophils. Her mentor is Steve Dumler, who is an international expert who helped discover this emerging pathogen back in the early 90’s. They are both unique in their expertise, being the only scientists in their field to focus their studies on the histopathologic effects and tissue injury caused by the host immune response to this organism. Dr. Scorpio’s research projects have mainly involved using animal models to investigate bacterial evasion of the innate immune response, which leads to unfortunate collateral tissue injury in the host, specifically hepatic histopathologic injury. Her initial studies focused on infection- induced neutrophil secretion of interleukin-8 (or murine homologs) and perpetuation of infection by recruitment of susceptible neutrophils. Antibody blockade of CXCR2 in mice decreased A. phagocytophilum tissue load by interrupting neutrophil recruitment, although tissue injury was unrelated to A. phagocytophilum tissue load.
Additional studies continued the investigation of infection and innate immunity, and in mice, A. phagocytophilum control is independent of phagocyte oxidase, inducible NO synthase (NOS2), tumor necrosis factor (TNF), and MyD88 Toll-like receptor signaling. We show that despite evasion of these host responses, phagocyte oxidase, NOS2, TNF, and MyD88 are activated and contribute to inflammation and hepatic injury more than A. phagocytophilum itself. With specific regard to NO, we tested the hypothesis that reactive nitrogen species (RNS) cause hepatic tissue damage from A. phagocytophilum infection and induction of NO from cytokine-activated macrophages. Mice received either water treated with a nonspecific inhibitor of inducible nitric oxide synthase, L-NAME, or untreated water for 7 to 10 d before infection and continuing thereafter. Overall, L-NAME treatment had a beneficial effect, resulting in lower histopathology scores and RNS levels compared with those of untreated mice.
Currently, 2 new projects are being developed, in addition to the current work proposed to study Bartonella infections in Sao Paolo, Brazil. One project involves the role of complement in A. phagocytophilum infection, and how the pathogen is able to evade or even exploit complement for entry into the neutrophil. A second project entails developing a canine co-infection model of A. phagocytophilum and Borrelia burgdorferi, and how matrix metalloproteases released by A. phagocytophilum infection enhances transmission and disease severity with B. burgdorferi.
Selected Publications
Publications:
Scorpio DG, Wachtman L, Tunin R, Barat NC, Garyu J, Dumler JS. (2008) Retrospective clinical and molecular analysis of conditioned laboratory dogs (Canis familiaris) with serologic reactions to Ehrlichia canis, Borrelia burgdorferi, and Rickettsia rickettsii. Journal of the American Association of Laboratory Animal Science, 47:23-28.
Scorpio DG, Ruben DS, Liao Z, Hildreth JE, Fletcher CA. (2008) Cervicovaginal evaluation in macaques used as a model for topical microbicide safety studies. Journal Medical Primatology 265, 37 Suppl 1:65-73.
Wagner A, Munter M, Makarov D, Nielsen M, Scorpio D, Kavoussi LR. (2008) Totally laparoscopic creation of a novel stapled orthotopic neobladder in the porcine model. Journal Endourology, 22:151-156.
Scorpio DG, Leutenegger C, Berger J, Barat NC, Madigan JE, Dumler JS. (2008) Sequential analysis of A. phagocytophilum msp2 transcription in murine and equine models of human granulocytic anaplasmosis. Clinical Vaccine Immunology, 15:418-424.
Choi KS, Webb T, Oelke M, Scorpio DG, Dumler JS. (2007) Differential innate immune cell activation and proinflammatory response in A. phagocytophilum infection. Infection and Immunity, 75:3124-3130.
Choi KS, Scorpio DG, Barat NC, Dumler JS. (2007) Msp2 variation in Anaplasma phagocytophilum in vivo does not stimulate T cell immune responses or interferon-? production. FEMS Immunology and Medical Microbiology 49:374-386.
Headley SA, Scorpio DG, Barat NC, Vidotto O, Dumler JS. (2006) Neorickettsia helminthoeca in dog, Brazil.
Emerging Infectious Diseases 12:1303-1304.
Scorpio DG, von Loewenich FD, Gobel H, Bogdan C, Dumler JS. (2006) Innate immune response to Anaplasma phagocytophilum contributes to hepatic injury. Clinical Vaccine Immunology 13:806-809.
Browning M, Garyu J, Dumler JS, Scorpio DG. (2006) Role of reactive nitrogen species on development of hepatic injury in a C57BL/6 model of human granulocytic anaplasmosis. Comparative Medicine 56:55-62.
Dumler JS, Choi KS, Garcia-Garcia JC, Barat NS, Scorpio DG, Garyu JW, Grab DJ, Bakken JS. (2005) Human Granulocytic Anaplasmosis and Anaplasma phagocytophilum. Emerging Infectious Diseases 11:1828-1834.
Scorpio DG, von Loewenich FD, Bogdan C, Dumler JS. (2005) Innate immune tissue injury and murine HGA: tissue injury in the murine model of granulocytic anaplasmosis relates to host innate immune response and not pathogen load.
Annals N Y Academy Science 1063:425-428.
Halasz CLG, Niedt GW, Kurtz CP, Scorpio DG, Bakken JS, Dumler JS. (2005) A case of Sweet syndrome associated with human granulocytic anaplasmosis. Archives Dermatology 141:887-889.
Jagannath SB, Kantsevoy SV, Vaughn CA, Chung SS, Cotton PB, Gostout CJ, Hawes RH, Pasricha PJ, Scorpio DG, Magee CA, Pipitone LJ, Kalloo AN. (2005) Peroral transgastric endoscopic ligation of fallopian tubes with long-term survival in a porcine model. Gastrointestinal Endoscopy 61:449-453.
Headley SA, Vidotto O, Scorpio DG, Dumler JS, Mankowski J. 2004. Suspected cases of Neorickettsia-like organisms in Brazilian dogs. Ann NY Acad Sci 1026:79-83.
Scorpio DG, Akkoyunlu M, Fikrig E, Dumler JS. 2004. CXCR2 blockade influences Anaplasma phagocytophilum propagation but not histopathology in the mouse HGA model. Clin Diag Lab Immun 11:963-68.
von Loewenich FD, Scorpio DG, Reischl U, Dumler JS, Bogdan C. 2004. Control of Anaplasma phagocytophilum, an obligate intracellular pathogen, in the absence of inducible nitric oxide synthase, phagocyte NADPH oxidase, tumor necrosis factor, toll-like receptor (TLR) 2 and 4, or the TLR adaptor molecule MyD88. Eur J Immunol 34:1789-97.
Choi KS, Scorpio DG, Dumler JS. 2004. Anaplasma phagocytophilum ligation to toll-like receptor (TLR) 2, but not to TLR4, activates macrophages for nuclear factor-kappa B nuclear translocation. J Infect Dis. 189:1921-5.
Scorpio DG, Caspersen K, Ogata H, Park J, Dumler JS. 2004. Restricted changes in major surface protein-2 (msp2) transcription after prolonged in vitro passage of Anaplasma phagocytophilum. BMC Microbiol. 4:1.
