Evaluation of viral sensitizer technology for improving influenza vaccine in an egg-basedmanufacturing process

Vaccination remains the most effective preventative measure for influenza infection. Seasonal influenza epidemics and the emergence of pandemic strains have increased the global demand for influenza vaccines, putting significant pressure on vaccine manufacturers. However, current vaccine manufacturing strategies rely primarily upon production in eggs, an age-old method that needs to be significantly improved. Recently, research from our lab identified a panel of novel compounds termed viral sensitizers (VSes) that increased virus production up to 1000 fold in cultured cells.

Design and synthesis of novel influenza M2 proton channel inhibitors with drug resistant antiviral activity

Seasonal influenza causes significant mortality and morbidity worldwide, and we are currently unprepared to mitigate a fatal pandemic outbreak like the 1918 Spanish Flu. A proven influenza antiviral target is the M2 viroporin, or viral ion channel. Amantadine, an M2 inhibitor was an effective antiviral for 20 years. However, current influenza antivirals are increasingly ineffective as viruses develop resistance. For example, the M2 mutation S31N is now present in >90% of influenza strains and confers resistance to adamantanes.

Radiochemistry for the Pharmacokinetic Evaluation of Novel Bone-Targeting Peptide Hormone Derivatives Year Two

This proposed research project is about development of new bone-targeting drug called PTHPEG- BP, this new compound will overcome shortages of current clinical peptide hormone PTH, and show better treatment efficacy and lower price then the latter; several new technologies will be used on research of this PTH, such as micro Positron Emission Tomography (PET/CT), and several of its characteristics will be identified such as structure, bioactivity, and metabolism inside body.

Investigating the biophysics and structural basis for state dependent drug blockade of persistent/late sodium current (INa(P)) in the heart using photoactivatable crosslinking unnatural amino acidsYR2

Electrical activity in the heart is controlled by the concerted activity of many proteins called ion-channels that regulate the transfer of different ions across cell membranes. Recently, researchers in biomedical science have identified that a particular component of sodium carrying ion-channel activity (called the persistent or late sodium current also known as INa(P)) played a major role in controlling the electrical activity of the heart. More recent research suggests that this late sodium current may be involved in various cardiac diseases.

The evaluation of pain management strategies for either caustic paste or cautery disbudding in dairy calves Year Two

Destruction of the horn bud in 4-6 wk old calves using either hot-iron or chemical disbudding is a common practice in the dairy industry. There is a limited body of research on the effects of chemical disbudding and the pain it causes to the animal as well as research on appropriate methods to mitigate the pain following this procedure, and research to identify appropriate pain managements is needed.

An omics study of plant responses to non-oncogenic Agrobacterium infection

ime-course biochemical and transcriptomic (gene expression) analysis of Nicotiana benthamiana in response to Agrobacterium infection and monoclonal antibody (mAB) expression. Host response to Agrobacterium infection may provide insight into novel approaches to increase recombinant protein production. Understanding changes in host gene expression may help identify targets for future engineering to limit negative impacts on the host due to infection and recombinant gene expression. Differential gene expression analysis may also reveal specific up-regulated host defenses (e.g.

Next-generation preclinical development andassessment of engraftment efficiency of Sernova’s Cell Pouch System™ in clinical islet transplantation

This fellowship will develop next generation Cell Pouch™ technology, through testing novel animal study (anti-cell death agents, insulin-producing mouse stem cells and islet health (metabolic engraftment efficiency) in parallel to a safety and efficacy (Phase I/II) clinical study of the Cell Pouch™ in Type 1 diabetic in which an in vitro measure of islet health will be correlated to in vivo graft function.

"Indanio Fellowship Year Two *Renewal, previous title ""Indanio Fellowship"""

The proposed project goals are five fold:

1) Generate and lead initiatives in drug discovery especially in the area of target identification/validation.

2) Generate transgenic zebrafish lines for nuclear receptor diseases related to oncology and metabolic diseases

3) Apply and supervise drug discovery on nuclear receptor ligand trap fish lines in the area of metabolic disease / cancer to extend state of the art research that leads to the discovery of new therapies

Development of an Integral Strategy for Model-based Dose Adaptation in Chemotherapy

The overall objective of this PDF project is to propose an integrated dose adaptation strategy that can be used in anticancer drug treatment. Indeed, many chemo agents used to treat tumors often induce dangerous side effects or toxicity, such as neutropenia [Crawford et al.] and hand-foot syndrome [Janusch et al.]. Since some tumors can only be destroyed by sufficiently high doses of chemotherapeutic agents, these harmful and lethal toxicities have become a main obstacle that limit the full use of the dosage of anticancer drugs or even force the discontinuation of chemo treatment.

Tumor Reduction and Enhanced Responsiveness to Radiation Therapy and Chemotherapy Via Selective Removal of Iron: Mechanism and Preclinical Evaluation

Objectives: The objectives of this study are to use in vitro and in vivo models to validate the hypothesis that the ironchelator, DIBI, can selectively inhibit the proliferation and survival of breast cancer cells and that the combination of this chelator with radiation or standard chemotherapeutic agents (e.g., cisplatin and docetaxel) increases the sensitivity of breast cancer cells to the treatment regime. In collaboration with Chelation Partners Inc.

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