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A Multivariate Approach For An Improved Assessment Of Pre-Erythrocytic Stage Therapies Targeting Plasmodium Vivax And Plasmodium Falciparum, Alison E. Roth
A Multivariate Approach For An Improved Assessment Of Pre-Erythrocytic Stage Therapies Targeting Plasmodium Vivax And Plasmodium Falciparum, Alison E. Roth
USF Tampa Graduate Theses and Dissertations
The malaria pre-erythrocytic stages have been identified as an ideal therapeutic target, but complex in vitro models for Plasmodium vivax and Plasmodium falciparum lack the efficiency needed for rapid screening and evaluation of new vaccines and drugs, especially targeting the P. vivax hypnozoite. To address this challenge, we employed a multi-parameter approach using “omics’” to identify pre-erythrocytic targets and biomarkers, guide phenotypic therapeutic screening, and study parasite functionality with innovative bioassays using highcontent screening. Herein, we discuss three novel bioassays formatted in 384-well plate systems with utilization of commercially-available materials and application of high-content imaging for rapid bio-image analysis. To …
Antimalarial Exoerythrocytic Stage Drug Discovery And Resistance Studies, Lynn Dong Blake
Antimalarial Exoerythrocytic Stage Drug Discovery And Resistance Studies, Lynn Dong Blake
USF Tampa Graduate Theses and Dissertations
Malaria is a devastating global health issue that affects approximately 200 million people yearly and over half a million deaths are caused by this parasitic protozoan disease. Most commercially available drugs only target the blood stage form of the parasite, but the only way to ensure proper elimination is to treat the exoerythrocytic stages of the parasite development cycle. There is a demand for the discovery of new liver stage antimalarial compounds as there are only two current FDA approved drugs for the treatment of liver stage parasites, one of which fails to eliminate dormant forms and the other inducing …
Hepatic Nutrient And Hormonal Regulation Of The Pancreatic-Derived Factor (Pander) Promoter, Whitney Ratliff
Hepatic Nutrient And Hormonal Regulation Of The Pancreatic-Derived Factor (Pander) Promoter, Whitney Ratliff
USF Tampa Graduate Theses and Dissertations
PANcreatic-DERived factor (PANDER, FAM3B) has been shown to regulate glycemic levels via interactions with both pancreatic islets and the liver. Although PANDER is predominantly expressed from the endocrine pancreas, recent work has provided sufficient evidence that the liver may also be an additional tissue source of PANDER production. At physiological levels, PANDER is capable of disrupting insulin signaling and promoting increased hepatic glucose production. As shown in some animal models, strong expression of PANDER, induced by viral delivery within the liver, induces hepatic steatosis. However, no studies to date have explicitly characterized the transcriptional regulation of PANDER from the liver. …
Development Of An Efficient Human Hepatocyte Culture Platform For Assessing Novel Therapeutic Efficacy Against Plasmodium Liver Parasites, Steven Patrick Maher
Development Of An Efficient Human Hepatocyte Culture Platform For Assessing Novel Therapeutic Efficacy Against Plasmodium Liver Parasites, Steven Patrick Maher
USF Tampa Graduate Theses and Dissertations
Malaria is a critical and global public health problem, affecting over 200 million people every year, resulting in over 500,000 deaths. A vaccine is not currently available and only one drug, primaquine, is effective against the dormant stages of Plasmodium vivax. Preclinical assessment of novel therapeutic drugs and vaccines is hampered by the lack of an in vitro liver model for P. falciparum and P. vivax. To provide a stable human hepatocyte-based culture platform for parasite development, we engineered a microfluidic bilayer device capable of both simple and complex culture methods, including perfusion and co-culture, to better understand the requirements …
Phenotypic Characterization Of The Pancreatic-Derived Factor (Pander) Knockout Mouse On Pure C57bl/6 Background, Shari Moak
USF Tampa Graduate Theses and Dissertations
PANcreatic-DERived Factor (PANDER), or FAM3B, is a 235-amino acid protein strongly expressed within and secreted from the endocrine pancreas. Research surrounding PANDER has revealed a large role for the protein in maintaining glucose homeostasis, as evidenced by several Ad-PANDER overexpressing murine models, our lab's pancreas-specific PANDER transgenic overexpressor, and most recently our mixed genetic C57/129J PANDER knockout (PANKO) mouse. However, PANDER's overall role in glycemic regulation and glucose homeostasis has yet to be studied in a purebred C57BL/6J PANDER knockout model. Here we present the first phenotypic characterization of our global PANDER knockout mouse on a C57BL/6J background (PANKO-C57) where …