Current Research and Scholarly Interests
Research Group, California Institute for Medical Research, San Jose; Div. of Infectious Diseases and Geographic Medicine, Stanford University, Medical School:
David A. Stevens, M.D.; Gabriele Sass, Ph.D.; Marife Martinez, B.S.1; Hasan Nazik, M. D.; Paulami Chatterjee, B.S.2
Research interests: Dr. Stevens' group studies the biology, pathogenesis, immunology, epidemiology and therapy of fungal and parasitic infections.
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, though disseminated coccidioidomycosis is also of major interest. Almost all models are murine, with 1 rabbit model; and 2 avian models (in collaboration with Veterinary School, Univ. of California, Davis). The laboratory has worked on development of panfungal conjugate vaccines, with special focus on Aspergillus and Coccidioides, including discovery of cross-reacting fungal proteins by mass spectroscopy and protein microarray, in collaboration with City of Hope, and using purified glycans supplied by an industrial partner. The chemotherapy of fungal infection is also under study including the evaluation of agents in vitro; for their efficacy, pharmacology, and toxicology in animal models and in human disease. In addition, the use of new drugs in the therapy of a parasitic infection, trypanosomiasis (Chagas? disease), is being studied in vitro and in mice. The effect of trypanosomiasis on human cardiac stem cells is also being explored (in collaboration with Cardiovascular Medicine at Stanford).
Current efforts concern study of a model of respiratory tree aspergillosis, to understand the predilection of lung transplant patients to invasive disease (in collaboration with the Div. of Pulmonary & Critical Care Med. at Stanford); and study of the biology of Aspergillus as it relates to lung biofilm and interaction with Pseudomonas aeruginosa, particularly in cystic fibrosis, and the molecular species involved (including collaborations with Dept. of Civil and Environmental Engineering, Dept. of Chemistry, and Div. of Pediatric Pulmonology, Stanford; Children?s Hosp. of Oakland Research Inst.; Univ. of California, Berkeley; Univ. of Sherbrooke, Quebec; MD Anderson Cancer Ctr., Houston; Univ. of Washington).
The laboratory has used molecular fingerprinting systems applied to the genomes of fungal species to develop tools to allow typing and differentiation of clinical isolates and for epidemiological and taxonomic purposes, particularly the epidemiology of Aspergillus and the Candida parapsilosis family. 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 collaborations with Latin America (Colombia and Brazil), the researchers have been involved in the study of paracoccidioidomycosis. Mammalian estradiol influence on Paracoccidioides pathogenesis was investigated by focusing on the block of morphogenetic transformation, the role of the fungal estradiol-binding protein, and production of estrogenic ligands by the fungus.
1 technical staff