Dr. Wright's research interests are:

1) Pneumocystis carinii biology
2) Pathogenesis of lung injury during Pneumocystis carinii pneumonia.

The rapid clearance of bacterial and fungal pathogens is essential to preserve the delicate structure and critical function of the lung. The opportunistic pathogen, Pneumocystis carinii, colonizes the alveolar epithelium of patients suffering from a variety of immunodeficiencies, including AIDS. Dr. Wright's laboratory uses an immunologically-reconstituted scid mouse model of Pneumocystis carinii pneumonia (PCP) to study the host response to infection. Scid mice lack functional lymphocytes and therefore develop active P. carinii infections. However, the adoptive transfer of congenic spleen cells, including CD4+ T lymphocytes, to P. carinii-infected scid mice results in inflammatory cell recruitment to sites of infection and organism clearance. They are now examining the earliest molecular signals (including cytokine and chemokine expression) produced at epithelial sites of P. carinii colonization, to determine which cell types and which soluble mediators are involved in targeting inflammatory cell recruitment. These studies will not only further our understanding of PCP, but may also provide insight into general mechanisms of lung defense.

In addition, they are examining the role of pulmonary inflammation in the pathology of PCP. As stated above, an intense CD4+ T lymphocyte-dependent inflammatory response is mounted at sites of infection in reconstituted scid mice. In many cases this inflammatory response is productive, and serves to resolve the infection. However, under certain circumstances the inflammatory response may actually contribute to the pulmonary injury and respiratory impairment observed in P. carinii pneumonia. They have begun studies using physiological and molecular measurements of lung injury to assess the in vivo role of P. carinii driven inflammation in PCP. They also plan to test specific anti-inflammatory agents to manipulate various aspects of the inflammatory response to determine the effect on lung injury. These studies will help define the role of inflammation in PCP, and further our understanding of pulmonary immunology.

• Gigliotti F, Wright TW. Pneumocystis: where does it live? PLoS Pathog. 2012 Nov; 8(11):e1003025.
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• Bello-Irizarry SN, Wang J, Olsen K, Gigliotti F, Wright TW. The Alveolar Epithelial Cell Chemokine Response to Pneumocystis Requires Adaptor Molecule MyD88 and Interleukin-1 Receptor but Not Toll-Like Receptor 2 or 4. Infect Immun. 2012 Nov; 80(11):3912-20.
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• Wang J, Wright TW, Gigliotti F. Immune Modulation as Adjunctive Therapy for Pneumocystis pneumonia. Interdiscip Perspect Infect Dis. 2011; 2011:918038.
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• Montgomery SL, Mastrangelo MA, Habib D, Narrow WC, Knowlden SA, Wright TW, Bowers WJ. Ablation of TNF-RI/RII expression in Alzheimer's disease mice leads to an unexpected enhancement of pathology implications for chronic pan-TNF-a suppressive therapeutic strategies in the brain. Am J Pathol. 2011 Oct; 179(4):2053-70.
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• Wang J, Gigliotti F, Bhagwat SP, George TC, Wright TW. Immune modulation with sulfasalazine attenuates immunopathogenesis but enhances macrophage-mediated fungal clearance during Pneumocystis pneumonia. PLoS Pathog. 2010; 6(8):e1001058.
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• Chess PR, Benson RP, Maniscalco WM, Wright TW, O'Reilly MA, Johnston CJ. Murine mechanical ventilation stimulates alveolar epithelial cell proliferation. Exp Lung Res. 2010 Aug; 36(6):331-41.
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• Desmet EA, Hollenbaugh JA, Sime PJ, Wright TW, Topham DJ, Sant AJ, Takimoto T, Dewhurst S, Maggirwar SB. Mixed Lineage Kinase 3 deficiency delays viral clearance in the lung and is associated with diminished influenza-induced cytopathic effect in infected cells. Virology. 2010 May 10; 400(2):224-32.
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• Bhagwat SP, Wright TW, Gigliotti F. Anti-CD3 antibody decreases inflammation and improves outcome in a murine model of Pneumocystis pneumonia. J Immunol. 2010 Jan 1; 184(1):497-502.
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• Pryhuber GS, Huyck HL, Bhagwat S, O'Reilly MA, Finkelstein JN, Gigliotti F, Wright TW. Parenchymal cell TNF receptors contribute to inflammatory cell recruitment and respiratory failure in Pneumocystis carinii-induced pneumonia. J Immunol. 2008 Jul 15; 181(2):1409-19.
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• Wang J, Gigliotti F, Bhagwat SP, Maggirwar SB, Wright TW. Pneumocystis stimulates MCP-1 production by alveolar epithelial cells through a JNK-dependent mechanism. Am J Physiol Lung Cell Mol Physiol. 2007 Jun; 292(6):L1495-505.
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• Gigliotti F, Crow EL, Bhagwat SP, Wright TW. Sensitized CD8+ T cells fail to control organism burden but accelerate the onset of lung injury during Pneumocystis carinii pneumonia. Infect Immun. 2006 Nov; 74(11):6310-6.
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• Bhagwat SP, Gigliotti F, Xu H, Wright TW. Contribution of T cell subsets to the pathophysiology of Pneumocystis-related immunorestitution disease. Am J Physiol Lung Cell Mol Physiol. 2006 Dec; 291(6):L1256-66.
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• Yee M, Vitiello PF, Roper JM, Staversky RJ, Wright TW, McGrath-Morrow SA, Maniscalco WM, Finkelstein JN, O'Reilly MA. Type II epithelial cells are critical target for hyperoxia-mediated impairment of postnatal lung development. Am J Physiol Lung Cell Mol Physiol. 2006 Nov; 291(5):L1101-11.
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• Vitiello PF, Staversky RJ, Gehen SC, Johnston CJ, Finkelstein JN, Wright TW, O'Reilly MA. p21Cip1 protection against hyperoxia requires Bcl-XL and is uncoupled from its ability to suppress growth. Am J Pathol. 2006 Jun; 168(6):1838-47.
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• Wells J, Haidaris CG, Wright TW, Gigliotti F. Active immunization against Pneumocystis carinii with a recombinant P. carinii antigen. Infect Immun. 2006 Apr; 74(4):2446-8.
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• Bruckner L, Gigliotti F, Wright T, Harmsen A, Notter RH, Chess P, Wang Z, Finkelstein J. Pneumocystis carinii infection sensitizes lung to radiation-induced injury after syngeneic marrow transplantation: role of CD4+ T cells. Am J Physiol Lung Cell Mol Physiol. 2006 Jun; 290(6):L1087-96.
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• Wells J, Haidaris CG, Wright TW, Gigliotti F. Complement and Fc function are required for optimal antibody prophylaxis against Pneumocystis carinii pneumonia. Infect Immun. 2006 Jan; 74(1):390-3.
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• Gigliotti F, Wright TW. Immunopathogenesis of Pneumocystis carinii pneumonia. Expert Rev Mol Med. 2005; 7(26):1-16.
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• Wang Z, Foye A, Chang Y, Chess PR, Wright TW, Bhagwat S, Gigliotti F, Notter RH. Inhibition of surfactant activity by Pneumocystis carinii organisms and components in vitro. Am J Physiol Lung Cell Mol Physiol. 2005 Jun; 288(6):L1124-31.
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• Wang J, Gigliotti F, Maggirwar S, Johnston C, Finkelstein JN, Wright TW. Pneumocystis carinii activates the NF-kappaB signaling pathway in alveolar epithelial cells. Infect Immun. 2005 May; 73(5):2766-77.
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• Disney MD, Stephenson R, Wright TW, Haidaris CG, Turner DH, Gigliotti F. Activity of Hoechst 33258 against Pneumocystis carinii f. sp. muris, Candida albicans, and Candida dubliniensis. Antimicrob Agents Chemother. 2005 Apr; 49(4):1326-30.
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• Swain SD, Wright TW, Degel PM, Gigliotti F, Harmsen AG. Neither neutrophils nor reactive oxygen species contribute to tissue damage during Pneumocystis pneumonia in mice. Infect Immun. 2004 Oct; 72(10):5722-32.
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• Wright TW, Pryhuber GS, Chess PR, Wang Z, Notter RH, Gigliotti F. TNF receptor signaling contributes to chemokine secretion, inflammation, and respiratory deficits during Pneumocystis pneumonia. J Immunol. 2004 Feb 15; 172(4):2511-21.
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• Gigliotti F, Harmsen AG, Wright TW. Characterization of transmission of Pneumocystis carinii f. sp. muris through immunocompetent BALB/c mice. Infect Immun. 2003 Jul; 71(7):3852-6.
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• Staversky RJ, Watkins RH, Wright TW, Hernady E, LoMonaco MB, D'Angio CT, Williams JP, Maniscalco WM, O'Reilly MA. Normal remodeling of the oxygen-injured lung requires the cyclin-dependent kinase inhibitor p21(Cip1/WAF1/Sdi1). Am J Pathol. 2002 Oct; 161(4):1383-93.
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• Gigliotti F, Haidaris CG, Wright TW, Harmsen AG. Passive intranasal monoclonal antibody prophylaxis against murine Pneumocystis carinii pneumonia. Infect Immun. 2002 Mar; 70(3):1069-74.
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• Wright TW, Notter RH, Wang Z, Harmsen AG, Gigliotti F. Pulmonary inflammation disrupts surfactant function during Pneumocystis carinii pneumonia. Infect Immun. 2001 Feb; 69(2):758-64.
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• Lee LH, Gigliotti F, Wright TW, Simpson-Haidaris PJ, Weinberg GA, Haidaris CG. Molecular characterization of KEX1, a kexin-like protease in mouse Pneumocystis carinii. Gene. 2000 Jan 25; 242(1-2):141-50.
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• Wright TW, Gigliotti F, Finkelstein JN, McBride JT, An CL, Harmsen AG. Immune-mediated inflammation directly impairs pulmonary function, contributing to the pathogenesis of Pneumocystis carinii pneumonia. J Clin Invest. 1999 Nov; 104(9):1307-17.
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• Wright TW, Johnston CJ, Harmsen AG, Finkelstein JN. Chemokine gene expression during Pneumocystis carinii-driven pulmonary inflammation. Infect Immun. 1999 Jul; 67(7):3452-60.
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• Simpson-Haidaris PJ, Courtney MA, Wright TW, Goss R, Harmsen A, Gigliotti F. Induction of fibrinogen expression in the lung epithelium during Pneumocystis carinii pneumonia. Infect Immun. 1998 Sep; 66(9):4431-9.
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• D'Angio CT, Johnston CJ, Wright TW, Reed CK, Finkelstein JN. Chemokine mRNA alterations in newborn and adult mouse lung during acute hyperoxia. Exp Lung Res. 1998 Sep-Oct; 24(5):685-702.
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• Johnston CJ, Wright TW, Rubin P, Finkelstein JN. Alterations in the expression of chemokine mRNA levels in fibrosis-resistant and -sensitive mice after thoracic irradiation. Exp Lung Res. 1998 May-Jun; 24(3):321-37.
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• Johnston CJ, Stripp BR, Piedbeouf B, Wright TW, Mango GW, Reed CK, Finkelstein JN. Inflammatory and epithelial responses in mouse strains that differ in sensitivity to hyperoxic injury. Exp Lung Res. 1998 Mar-Apr; 24(2):189-202.
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• Johnston CJ, Wright TW, Reed CK, Finkelstein JN. Comparison of adult and newborn pulmonary cytokine mRNA expression after hyperoxia. Exp Lung Res. 1997 Nov-Dec; 23(6):537-52.
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• Wright TW, Johnston CJ, Harmsen AG, Finkelstein JN. Analysis of cytokine mRNA profiles in the lungs of Pneumocystis carinii-infected mice. Am J Respir Cell Mol Biol. 1997 Oct; 17(4):491-500.
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• Simpson-Haidaris PJ, Wright TW, Earnest BJ, Hui Z, Neroni LA, Courtney MA. Cloning and characterization of a lung-specific cDNA corresponding to the gamma chain of hepatic fibrinogen. Gene. 1995 Dec 29; 167(1-2):273-8.
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• Wright TW, Gigliotti F, Haidaris CG, Simpson-Haidaris PJ. Cloning and characterization of a conserved region of human and rhesus macaque Pneumocystis carinii gpA. Gene. 1995 Dec 29; 167(1-2):185-9.
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• Wright TW, Bissoondial TY, Haidaris CG, Gigliotti F, Haidaris PJ. Isoform diversity and tandem duplication of the glycoprotein A gene in ferret Pneumocystis carinii. DNA Res. 1995; 2(2):77-88.
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• Wright TW, Simpson-Haidaris PJ, Gigliotti F, Harmsen AG, Haidaris CG. Conserved sequence homology of cysteine-rich regions in genes encoding glycoprotein A in Pneumocystis carinii derived from different host species. Infect Immun. 1994 May; 62(5):1513-9.
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• Lawrence SO, Wright TW, Francis CW, Fay PJ, Haidaris PJ. Purification and functional characterization of homodimeric gamma B-gamma B fibrinogen from rat plasma. Blood. 1993 Oct 15; 82(8):2406-13.
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• Gigliotti F, Haidaris PJ, Haidaris CG, Wright TW, Van der Meid KR. Further evidence of host species-specific variation in antigens of Pneumocystis carinii using the polymerase chain reaction. J Infect Dis. 1993 Jul; 168(1):191-4.
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• Haidaris PJ, Wright TW, Gigliotti F, Fallon MA, Whitbeck AA, Haidaris CG. In situ hybridization analysis of developmental stages of Pneumocystis carinii that are transcriptionally active for a major surface glycoprotein gene. Mol Microbiol. 1993 Mar; 7(5):647-56.
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• Haidaris PJ, Wright TW, Gigliotti F, Haidaris CG. Expression and characterization of a cDNA clone encoding an immunodominant surface glycoprotein of Pneumocystis carinii. J Infect Dis. 1992 Nov; 166(5):1113-23.
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• Gigliotti F. Antigenic variation of a major surface glycoprotein of Pneumocystis carinii. J Protozool. 1991 Nov-Dec; 38(6):4S-5S.
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• Haidaris CG, Wright TW, Gigliotti F, Haidaris PJ. Molecular cloning and characterization of ferret Pneumocystis carinii gp120. J Protozool. 1991 Nov-Dec; 38(6):5S-6S.
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