Our approach extends in four major areas of experimental mycology that directly impacts all areas of risk stratification, epidemiology, diagnosis detection of resistance and treatment of all opportunistic mycoses:
- In vitro screening for novel antifungal agents. We are using a state-of-the-art imaging system to study in real time hyphal morphogenesis susceptibility, resistance or tolerance in response to immune cells, drugs and mutants.
- Development of alternative mini-host organisms, such as fruit flies, zebra fish and C elegans as an easy, inexpensive, fast and genetically amenable model to study all medically important fungi (Candida, Aspergillus, Mucorales, Fusarium).
- Development of mamamalian models suitable for studying antifungal pharmacology and fungal pathogenesis of Candida, Aspergillus and other emerging invasive fungal infections.
- Characterization of the immune-pharmacology of antifungal agents.
- Fungal immunology program: CAR T cells (in collaboration with Pappanaicken Kumar, M.D., Instructor, Department of Pediatrics), check point inhibitors (in collaboration with Prema Robinson, Ph.D., Associate Professor, Department of Infectious Diseases Research), and Aspergllus virulence, NK activity against Fusarium/Scedosporium (in collaboration with Katy Rezvani, M.D., Ph.D., Professor, Department of Stem Cell Transplantation and Cellular Therapy).
The Kontoyiannis Laboratory has contributed to several discoveries. Among them:
- Establishment of Drosophila melanogaster as a novel model to study fungal pathogenesis and treatment
- First description of the fungal exotoxin gliotoxin in angiogenesis
- Synergy of calcineurin and ergosterol pathway inhibition against molds
- Development of subacute experimental models of aspergillosis in murine hosts
- His insight regarding paradoxical effect of the fungal cell wall inhibiting agents against fungi
- Introduction of peptidomimetic approaches to treatment and diagnosis in experimental systems
- Description of apoptosis in Mucorales
- Introduction of the concept of sequential antifungal exposure in in vitro and virulence testing
- Immunomodulatory activity of the echinocandins
- Study of association of fitness loss and resistance in fungi