The Mycology Research Unit: In Vivo Induced Fungal Antigens Program Project consists of four interrelated research projects and a Clinical Resource Core organized around the identification of C. albicans and A. fumigatus proteins expressed during human infections. The unifying hypothesis of the Program is that selected in vivo induced proteins contribute to the pathogenesis of invasive fungal infections and have potential applications as vaccine, diagnostic and therapeutic targets. The Core, run by Dr. Wingard (University of Florida; UF) will collect sera and tissue samples from patients with C. albicans and A. fumigatus infections. The sera will be used extensively in each of the projects. In Project 1 (Candida antigens involved in site-specific virulence), Dr. Nguyen (UF) will study in vivo induced antigens that she and Dr. Clancy identified by screening a genomic expression library with sera from patients with candidiasis. The contributions of the in vivo induced antigens to pathogenesis will be assessed in models of mucosal and systemic candidiasis. She will also characterize the humoral immune response against recombinant antigens in the serum of patients with candidiasis and controls. In Project 2 (A proteomic approach to host humoral immune response), Dr. Liu (UC-Irvine) will construct C. albicans cell wall protein and blood-induced protein arrays and probe them with sera from patients who survived or died from candidemia. Her goal is to identify immunogenic antigens associated with good prognosis. In Project 3 (Candida in vivo expressed protein as a mannan carrier), Dr. Cutler (TRIC,La) will use cell wall antigens identified in Projects 1 and 2 as carrier proteins in a conjugate mannan vaccine against hematogenous candidiasis. Finally, in Project 4 (Identification of In vivo Induced A. fumigatus Antigens), Dr. Clancy (UF) will adapt the serum-based screening that he and Dr. Nguyen developed to screen A. fumigatus expression libraries. In vivo induced A. fumigatus antigens can then be studied using our investigations of C. albicans antigens as models.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI061537-02
Application #
6901851
Study Section
Special Emphasis Panel (ZAI1-HSD-M (M2))
Program Officer
Duncan, Rory A
Project Start
2004-06-15
Project End
2009-05-31
Budget Start
2005-06-01
Budget End
2006-05-31
Support Year
2
Fiscal Year
2005
Total Cost
$742,887
Indirect Cost
Name
University of Florida
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
969663814
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Cartmell, Jonathan; Paszkiewicz, Eugenia; Dziadek, Sebastian et al. (2015) Synthesis of antifungal vaccines by conjugation of ?-1,2 trimannosides with T-cell peptides and covalent anchoring of neoglycopeptide to tetanus toxoid. Carbohydr Res 403:123-34
Du, Chen; Wingard, John R; Cheng, Shaoji et al. (2012) Serum IgG responses against Aspergillus proteins before hematopoietic stem cell transplantation or chemotherapy identify patients who develop invasive aspergillosis. Biol Blood Marrow Transplant 18:1927-34
Nguyen, M Hong; Leather, Helen; Clancy, Cornelius J et al. (2011) Galactomannan testing in bronchoalveolar lavage fluid facilitates the diagnosis of invasive pulmonary aspergillosis in patients with hematologic malignancies and stem cell transplant recipients. Biol Blood Marrow Transplant 17:1043-50
Cutler, Jim E; Corti, Miriam; Lambert, Patrick et al. (2011) Horizontal transmission of Candida albicans and evidence of a vaccine response in mice colonized with the fungus. PLoS One 6:e22030
Vadnerkar, Aniket; Toyoda, Yoshiya; Crespo, Maria et al. (2011) Age-specific complications among lung transplant recipients 60 years and older. J Heart Lung Transplant 30:273-81
Vadnerkar, Aniket; Clancy, Cornelius J; Celik, Umit et al. (2010) Impact of mold infections in explanted lungs on outcomes of lung transplantation. Transplantation 89:253-60
Mitsani, Dimitra; Nguyen, M Hong; Kwak, Eun J et al. (2010) Cytomegalovirus disease among donor-positive/recipient-negative lung transplant recipients in the era of valganciclovir prophylaxis. J Heart Lung Transplant 29:1014-20
Mochon, A Brian; Jin, Ye; Ye, Jin et al. (2010) Serological profiling of a Candida albicans protein microarray reveals permanent host-pathogen interplay and stage-specific responses during candidemia. PLoS Pathog 6:e1000827
Vadnerkar, Aniket; Nguyen, M Hong; Mitsani, Dimitra et al. (2010) Voriconazole exposure and geographic location are independent risk factors for squamous cell carcinoma of the skin among lung transplant recipients. J Heart Lung Transplant 29:1240-4
Hao, Binghua; Clancy, Cornelius J; Cheng, Shaoji et al. (2009) Candida albicans RFX2 encodes a DNA binding protein involved in DNA damage responses, morphogenesis, and virulence. Eukaryot Cell 8:627-39

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