Praveen R. Juvvadi, Ph.D.

Research Overview

Invasive fungal infections caused by species of Aspergillus, Candida, and Cryptococcus contribute to significant morbidity and mortality in immunocompromised patients. Dr. Juvvadi’s laboratory is focused on research on Aspergillus fumigatus that causes Invasive Aspergillosis (IA) disease in immunocompromised patients including children. The mortality rate for IA is rising due to emerging resistance to guideline-recommended treatments using the azoles and echinocandins. While the growing immunocompromised patient population has outpaced antifungal development, the increasing incidence of antifungal resistance is further hampering effective treatment. As a result, there is a greater and urgent need for innovative approaches to exploring broad, new antifungal targets with novel mechanisms of action. A fundamental understanding of fungal growth and pathogenesis mechanisms is necessary to design effective antifungal therapeutics.

Dr. Juvvadi’s research is primarily directed toward identifying genes that are indispensable for fungal growth, drug response, and virulence by utilizing various molecular strategies, including genetic, biochemical, and proteomic techniques and animal models of infection. His laboratory research has demonstrated the importance of calcineurin, a calcium-calmodulin-dependent protein phosphatase, for fungal growth and virulence. The overall goal is to elucidate the calcineurin-dependent molecular mechanisms controlling fungal growth, pathogenesis, and drug resistance, utilizing whole proteomic and lipidomic approaches which will ultimately enable the identification of fungal-specific targets to help design potentially more effective strategies to combat IA.

Dr. Juvvadi’s research program is supported through grants from the National Institute of Allergy and Infectious Diseases (NIH).

Ongoing Research:

• Calcineurin regulatory network control of Aspergillus fumigatus hyphal growth.
• Calcineurin role in Aspergillus fumigatus antifungal response and resistance mechanisms.
• Structural approaches to design novel fungal-specific calcineurin inhibitors.
• Protein Kinase A control over Aspergillus fumigatus autophagy and pathogenesis mechanisms.

Impact: Antifungal drug resistance is rapidly emerging and crippling therapeutic options for IA. Novel approaches to deciphering antifungal resistance pathways are urgently needed. These holistic approaches and studies will provide a mechanistic understanding of how the calcineurin network drives antifungal response and resistance in Aspergillus fumigatus, generating substantial future translational potential for improved strategies to combat invasive fungal disease.