Dr. Stevens's group studies the biology, immunology, epidemiology and therapy of fungal infections. They are using molecular fingerprinting systems applied to the genomes of Candida species to develop tools to allow typing and differentiation of clinical isolates and for epidemiological and taxonomic purposes. Fungal signatures are sought in development of rapid and sensitive diagnostic techniques. Animal models are developed and used to study differences in virulence in fungal strains, their biochemical characterization and interaction with host defenses, particularly the role of therapy with recombinant cytokines and other immunomodulators, and preclinical studies of diagnosis. The infections most intensively investigated, with respect to pathogenesis or therapy, are pulmonary and disseminated aspergillosis, coccidioidal meningitis and pulmonary blastomycosis. The laboratory is working on development of vaccines against Coccidioides and Aspergillus. The chemotherapy of fungal infection is also under study including the evaluation of agents in vitro, and for their efficacy, pharmacology, and toxicology in animal models and in human disease. The laboratory is, in addition, a clinical reference laboratory for fungal and actinomycete susceptibility testing, and body fluid antifungal drug concentration determinations, for hospitals in the area. In collaborations with Latin America, the researchers are involved in the study of paracoccidioidomycosis. Mammalian estradiol influence on Paracoccidioides pathogenesis is being investigated by focusing on the block of morphogenetic transformation and the role of the fungal estradiol-binding protein. Paracoccidioides gene expression during morphogenesis, and the events in hormone-mediated block, are under study with DNA microarray technology.