My laboratory research centers on infections that emerge when the body’s innate and adaptive defenses are compromised.  We study three different opportunistic pathogens that take advantage of immunodeficiency to cause infection.

The fungus Candida is a common commensal in humans and survives on both cutaneous and mucocutaneous surfaces.  A breakdown in mucosal integrity or adaptive immunity results in the conversion of Candida from a commensal to a pathogen.  Phagocytic cells are critical for protection against Candida.  We examine the role of specific antibody in promoting phagocytosis and killing of Candida.  As a novel approach to therapy, we are studying the efficacy of photosensitizing agents to treat infection by Candida under conditions where antifungal resistance has emerged.  Photosensitizers are organic molecules that, when irradiated, interact with molecular oxygen to generate reactive oxygen species that are toxic for the target cell.  Current efforts focus on metabolic pathways in Candida that can be modulated to increase the sensitivity of the organism to killing via oxidative stress using photosensitizing agents. 

Collaborators: 
Melanie Wellington, M.D./Ph.D., Dept. of Pediatrics;
Thomas H. Foster, Ph.D., Dept of Imaging Sciences.

The fungus Pneumocystis carinii causes a pneumonia that is a major cause of morbidity and mortality in AIDS, cancer and transplant patients.  We use molecular biology approaches to identify and characterize recombinant antigens as potential vaccine candidates, based on their reactivity with antibodies that demonstrate protection against infection.  Animal models of infection are in place to examine both active and passive immunization strategies using recombinant P. carinii antigens.  Current studies focus on common antigens shared by mouse and human Pneumocystis.

Collaborators: 
Frank Gigliotti, M.D. and Terry Wright, Ph.D., Department of Pediatrics;
P.J. Simpson-Haidaris, Ph.D., Dept. of Medicine.

The gram-negative bacterium Pseudomonas aeruginosa is ubiquitous in the environment and does not cause infection in the healthy host.  However, P. aeruginosa frequently causes infections in patients with burn wounds, corneal damage or cystic fibrosis that are difficult to treat.  Damage to host tissue is mediated by a variety of extracellular products that contribute to virulence.  We recently made the observation that the signaling molecule nitric oxide (NO) is an important regulator of virulence factor production in P. aeruginosa.  Current studies focus on the regulation of P. aeruginosa virulence factor gene expression by NO, and the interaction of P. aeruginosa with the host, using phagocytes and the nematode Caenorhabditis elegans as model systems. 

Collaborator:
Barbara H. Iglewski, Ph.D., Dept. of Microbiology and Immunology

Chabrier-Rosello Y, Foster TH, Mitra S, Haidaris CG Respiratory deficiency enhances the sensitivity Candida to photodynamic treatment. Photochem Photobiol. 2008 Nov-Dec;84(6):1605

Chabrier-Roselló Y, Foster TH, Mitra S, Haidaris CG.  Respiratory deficiency enhances the sensitivity of the pathogenic fungus Candida to photodynamic treatment. Photochem. Photobiol. 2008 Sep-Oct;84(5):1141-8. Epub 2008 Jan 29. PMID: 18248505

Wellington M, Dolan K, Haidaris CG.  Monocyte responses to Candida albicans are enhanced by antibody in cooperation with antibody-independent pathogen recognition.  FEMS Immunol. Med. Microbiol. 2007 Oct;51(1):70-83. Epub 2007 Jul 4.  PMID: 17610517

Van Alst NE, Picardo KF, Iglewski BH, Haidaris CG.  Nitrate sensing and metabolism modulate motility, biofilm formation, and virulence in Pseudomonas aeruginosa.  Infect. Immun. 2007 Aug;75(8):3780-90. Epub 2007 May 25.  PMID: 17526746

Foster DC, Piekarz KH, Murant TI, LaPoint R, Haidaris CG, Phipps RP.  Enhanced synthesis of proinflammatory cytokines by vulvar vestibular fibroblasts: implications for vulvar vestibulitis.  Am. J. Obstet. Gynecol. 2007 Apr;196(4):346.e1-8.  PMID: 17403416

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.  PMID: 16552076

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.  PMID: 16368994

Chabrier-Roselló Y, Foster TH, Pérez-Nazario N, Mitra S, Haidaris CG.  Sensitivity of Candida albicans germ tubes and biofilms to photofrin-mediated phototoxicity. Antimicrob. Agents Chemother. 2005 Oct;49(10):4288-95.  PMID: 16189110