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Search Results to Praveen Juvvadi
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One or more keywords matched the following properties of
Juvvadi, Praveen
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research overview
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Invasive fungal infections caused by species of Aspergillus, Candida, and Cryptococcus contribute to significant morbidity and mortality in immunocompromised patients. Our laboratory’s research is focused on the human fungal pathogen, Aspergillus fumigatus, that causes deadly Invasive Aspergillosis (IA) disease in immunocompromised patients. 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 an urgent need for innovative approaches to exploring broad, new antifungal targets with novel mechanisms of action. To design effective antifungal therapeutics a fundamental understanding of fungal growth and pathogenesis mechanisms is necessary.
Our laboratory research is primarily directed toward identifying genes that are indispensable for fungal growth, drug response, and virulence by utilizing a variety of molecular strategies including genetic, biochemical, proteomic techniques and animal models of infection. Over the last 15 years our laboratory research has demonstrated the importance of calcineurin (CN) a calmodulin-dependent protein phosphatase for fungal growth and drug resistance. Our broader whole CN proteomic and phosphoproteomic approaches uncovered several cell wall- and cell membrane-related proteins as potential CN effectors. We also defined unique changes in the A. fumigatus CN proteome in direct response to azole and echinocandin antifungals. Our first fungal CN ternary complex crystal structure-guided inhibitor strategies showed that targeting CN was effective in animal models.
Our overall goal is to elucidate the molecular mechanisms controlling fungal growth, pathogenesis, and drug resistance which will ultimately enable us to identify fungal-specific targets to help design potentially more effective strategies to combat IA.
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. Our studies will provide mechanistic understanding of how the CN network drives antifungal response and resistance in A. fumigatus, generating substantial future translational potential for improved strategies to combat invasive fungal disease.
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One or more keywords matched the following items that are connected to
Juvvadi, Praveen
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Concept
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Drug Resistance, Fungal
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Concept
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Drug Resistance, Multiple, Fungal
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Grant
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Structural Biological Development of Fungal-Specific Calcineurin Inhibitors
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Academic Article
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The Aspergillus fumigatus P-type Golgi apparatus Ca2+/Mn2+ ATPase PmrA is involved in cation homeostasis and cell wall integrity but is not essential for pathogenesis.
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Academic Article
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In vitro activity of calcineurin and heat shock protein 90 Inhibitors against Aspergillus fumigatus azole- and echinocandin-resistant strains.
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Academic Article
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Transcriptional activation of heat shock protein 90 mediated via a proximal promoter region as trigger of caspofungin resistance in Aspergillus fumigatus.
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Identification of a key lysine residue in heat shock protein 90 required for azole and echinocandin resistance in Aspergillus fumigatus.
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Academic Article
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Heat shock protein 90 (Hsp90): A novel antifungal target against Aspergillus fumigatus.
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Calcineurin as a Multifunctional Regulator: Unraveling Novel Functions in Fungal Stress Responses, Hyphal Growth, Drug Resistance, and Pathogenesis.
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Academic Article
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Calcineurin Orchestrates Hyphal Growth, Septation, Drug Resistance and Pathogenesis of Aspergillus fumigatus: Where Do We Go from Here?
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Novel motif in calcineurin catalytic subunit is required for septal localization of calcineurin in Aspergillus fumigatus.
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Calcineurin in fungal virulence and drug resistance: Prospects for harnessing targeted inhibition of calcineurin for an antifungal therapeutic approach.
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Aspergillus fumigatus Cyp51A and Cyp51B Proteins Are Compensatory in Function and Localize Differentially in Response to Antifungals and Cell Wall Inhibitors.
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In Vitro Activity of APX2041, a New Gwt1 Inhibitor, and In Vivo Efficacy of the Prodrug APX2104 against Aspergillus fumigatus.
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Tuning sterol extraction kinetics yields a renal-sparing polyene antifungal.
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