Dr. Fortwendel’s research focuses on deciphering novel mechanisms through which the pathogenic fungus, Aspergillus fumigatus, causes disease. A. fumigatus is the most common mold pathogen of patients with blood cancers, causing high morbidity and mortality.
“A major hurdle for designing drugs to combat fungal infections is that fungal and human cell physiology are very similar,” Dr. Fortwendel said. “In fact, our current antifungal therapies are quite toxic to the patient, and physicians administering these drugs are continually balancing antifungal activity with patient toxicity.”
Previous work in Dr. Fortwendel’s laboratory has shown Ras proteins to be major regulators of A. fumigatus virulence, orchestrating cellular processes required for growth inside the human host. Ras is an important signal transduction protein, necessary for relaying external signals to the internal cell machinery. In pathogenic fungi, Ras activity is especially important for formation of the long tubular structures – known as ‘hyphae’ – developed by fungi to invade the human body.
“We have identified novel, fungal-specific protein domains that define fundamental differences between fungal and human Ras proteins. According to Dr. Fortwendel, his goal is to fully define the impact of these fungal-specific protein domains to Ras biology.
“By completing these studies, we will begin to understand novel means through which Ras proteins mediate fungal adaptation to the host environment and subsequent hyphal growth,” he said. “In doing so, we expect to identify novel virulence traits for A. fumigatus and, in the long term, devise new ways to inhibit invasive fungal growth with minimal toxicity.”
Dr. Fortwendal said this research not only impacts A. fumigatus infections, but will potentially identify fungal-specific drug targets present in all medically important fungi. “Discovering new ways to inhibit fungal growth is an essential step in the continued battle against these deadly invasive fungal infections.”
