Our approach extends in five 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), checkpoint inhibitors 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
- Establishment of zebra fish as a robust mini-host model to study the interface mucosal injury and fungal invasion
- 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
- Studies in mechanobiology of Mucorales