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Dr. MARIA JOSÉ SOARES MENDES GIANNINI Associate Professor Departamento de Análises Clínicas Faculdade de Ciências Farmacêuticas -UNESP Rua Expedicionários do Brasil, 1621 CEP: 14801-902 Telephone: +55 16-3301-6556 Fax: +55 16 3301-6547 E-mail: email@example.com SUMMARY OF RESEARCH ACTIVITY Our group is engaged in researching the relationship between the fungal pathogen and its host. In this endeavor, we have developed a cell-culture model designed to unravel the steps involved in the process of infection, from the first contact of the fungus to the adhesion and invasion events that culminate in its establishment inside the mammalian cell. Currently, we are studying the adhesins produced and the signaling events that occur during contact between cells of Paracoccidioides brasiliensis and epithelial and mononuclear cells, employing immunocytochemical, molecular and proteomic methods. By these methods, not only have we demonstrated that P. brasiliensis has the capacity to invade human and animal epithelial cell lines, but have also shown a correlation, for the first time, between the degree of virulence and adhesion capacity of different strains of the fungus. Further, we proved that their pattern of adhesion to individual components of the extracellular matrix, such as types I and IV collagen, laminin, fibronectin and entactin, differed between samples showing different degrees of virulence. Recently, a 30 kDa adhesin was isolated from P. brasiliensis that showed an ability to bind laminin. This protein was expressed more strongly in an isolate of the fungus that possessed a high capacity for adhesion. In experiments to elucidate the role of 30 and 43 kDa fungal proteins in interactions with epithelial cells, the adhesion of P. brasiliensis was found to be greatly inhibited when the epithelial cells were pretreated with these adhesins. Among the components of the host cytoskeleton, we have shown that this fungus probably makes use of actin and tubulin to gain entrance to the cell and that cytokeratin also seems to play an important part. Finally, in the same mammalian cell cultures, it was observed that P. brasiliensis and some of its components were capable of inducing apoptosis in epithelial cells. Another line of research in this laboratory concerns the molecular epidemiology of the major fungi affecting immunocompetent and immunodeficient patients, with the aim of finding out which are the main classes of molecules involved in human fungal disease and recording the sensitivity profiles of these organisms to the main antifungal agents used in clinical treatment. We have an ongoing interest in the study of isolates that show resistance to antifungal drugs, in particular the azoles, in the hope of discovering new mechanisms of resistance. In very recent work we have applied representational difference analysis to identifying the genes likely to be involved in the fungal infection process. We also contribute to the FAPESP BIOTA project and its database, BIOprospecTA, screening plant species of the cerrado (savannah-like scrub forest) and Atlantic Forest biomes for antifungal substances. MAIN PUBLICATIONS Barbosa MS, Bao SN, Andreotti PF, de Faria FP, Felipe MS, dos Santos Feitosa L, Mendes- Giannini MJ, Soares CM. Glyceraldehyde-3-phosphate dehydrogenase of Paracoccidioides brasiliensis is a cell surface protein involved in fungal adhesion to extracellular matrix proteins and interaction with cells. Infect Immun. 2006 Jan;74(1):382-9. Mendes-Giannini MJ, Soares CP, da Silva JL, Andreotti PF. Interaction of pathogenic fungi with host cells: Molecular and cellular approaches. FEMS Immunol Med Microbiol. 2005 Sep 1;45(3):383-94. Review. Andreotti PF, Monteiro da Silva JL, Bailao AM, Soares CM, Benard G, Soares CP, Mendes- Giannini MJ. Isolation and partial characterization of a 30 kDa adhesin from Paracoccidioides brasiliensis. Microbes Infect. 2005 May;7(5-6):875-81. Mendes-Giannini MJ, Hanna SA, da Silva JL, Andreotti PF, Vincenzi LR, Benard G, Lenzi HL, Soares CP. Invasion of epithelial mammalian cells by Paracoccidioides brasiliensis leads to cytoskeletal rearrangement and apoptosis of the host cell. Microbes Infect. 2004 Aug;6(10):882-91 Benard G, Kavakama J, Mendes-Giannini MJ, Kono A, Duarte AJ, Shikanai-Yasuda MA. Contribution to the natural history of paracoccidioidomycosis: identification of the primary pulmonary infection in the severe acute form of the disease--a case report. Clin Infect Dis. 2005 Jan 1;40(1):e1-4. Romano CC, Mendes-Giannini MJ, Duarte AJ, Benard G. The role of interleukin-10 in the differential expression of interleukin-12p70 and its beta2 receptor on patients with active or treated paracoccidioidomycosis and healthy infected subjects.Clin Immunol. 2005 Jan;114(1):86-94. Martins-Diniz JN, da Silva RA, Miranda ET, Mendes-Giannini MJ. Monitoring of airborne fungus and yeast species in a hospital unit] Rev Saude Publica. 2005 Jun;39(3):398-405. Baeza, LC; Giannini,MJ Strain differentiation of Trichophyton rubrum by random amplification of polymorphic DNA (RAPD). Rev Inst Med Trop Sao Paulo. 2004 Nov-Dec;46(6):339-41. Raso TF, Werther K, Miranda ET, Mendes-Giannini MJ. Cryptococcosis outbreak in psittacine birds in Brazil. Med Mycol. 2004 Aug;42(4):355-62. Romano CC, Mendes-Giannini MJ, Duarte AJ, Benard G. IL-12 and neutralization of endogenous IL-10 revert the in vitro antigen-specific cellular immunosuppression of paracoccidioidomycosis patients. Cytokine. 2002 May 7;18(3):149-57. Cacere CR, Romano CC, Mendes Giannini MJ, Duarte AJ, Benard G. The role of apoptosis in the antigen-specific T cell hyporesponsiveness of paracoccidioidomycosis patients.Clin Immunol. 2002 Nov;105(2):215-22. Biselli PJ, Juvenale M, Mendes-Giannini MJ, Duarte AJ, Benardi G. IgE antibody response to the main antigenic component of Paracoccidioides brasiliensis in patients with paracoccidioidomycosis.Med Mycol. 2001 Dec;39(6):475-8. Benard G, Romano CC, Cacere CR, Juvenale M, Mendes-Giannini MJ, Duarte AJ. Imbalance of IL-2, IFN-gamma and IL-10 secretion in the immunosuppression associated with human paracoccidioidomycosis. Cytokine. 2001 Feb 21;13(4):248-52. Verweij PE, Figueroa J, Van Burik J, Holdom MD, Dei-Cas E, Gomez BL, Mendes-Giannini MJ. Clinical applications of non-culture based methods for the diagnosis and management of opportunistic and endemic mycoses.Med Mycol. 2000;38 Suppl 1:161-71. Review. Mendes-Giannini MJ, Taylor ML, Bouchara JB, Burger E, Calich VL, Escalante ED, Hanna SA, Lenzi HL, Machado MP, Miyaji M, Monteiro Da Silva JL, Mota EM, Restrepo A, Restrepo S, Tronchin G, Vincenzi LR, Xidieh CF, Zenteno E. Pathogenesis II: fungal responses to host responses: interaction of host cells with fungi. Med Mycol. 2000;38 Suppl 1:113-23. Review Hanna SA, Monteiro da Silva JL, Giannini MJ. Adherence and intracellular parasitism of Paracoccidioides brasiliensis in Vero cells. Microbes Infect. 2000 Jul;2(8):877-84.
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