Pharmacy and Pharmaceutical Sciences Commons^™

Application Of Informatics Tools To Facilitate The Practice Of Precision Medicine With Genomic Testing And Clinical Data, Michael Sayer

Pharmaceutical Sciences (PhD) Dissertations

The practice of precision medicine considers a variety of sources of information to optimize patient care. Factors such as patient demographics, clinical history, and lab test values have well understood effects on treatment outcomes and influence decision making. However, effective inclusion of biomolecular data such as protein expression and DNA sequencing data within the practice of precision medicine needs continued study. Informatics tools offer solutions to allow these complex data sources to be effectively embraced. Utilization of informatics tools to visualize data pertaining to the gene selection practices of pharmacogenomic (PGx) tests effectively communicated large amounts of information into concise …

Genetic Mutations Of KCa2.3 And KCa3.1 Channels Affect Ca2+ Sensitivity, Razan Orfali

Pharmaceutical Sciences (PhD) Dissertations

The Ca²⁺-activated potassium channels K_Ca channels are a unique family of potassium channels activated by intracellular calcium. K_Ca channels are critical for maintaining K⁺ homeostasis and modulate several physiological processes, from the firing properties of neurons to the control of the transmitter release. The Ca²⁺ sensitivity of these channels allows intracellular Ca²⁺ to regulate the electrical activity of the cell membrane. Increased Ca²⁺ sensitivity of K_Ca channels caused by gain of function mutations (GOF) in the KCNN genes results in a broad spectrum of human channelopathies, including Zimmermann- Laband syndrome (ZLS), …

Influences Of Host Cytokine Signaling On Kshv Infection In Tonsil-Derived B Lymphocytes, Nedaa Alomari

Pharmaceutical Sciences (PhD) Dissertations

Kaposi sarcoma-associated herpesvirus (KSHV) is the etiologic agent of kaposi sarcoma. It is also associated with the B cell lymphoproliferative disorders, primary effusion lymphoma (PEL), multicentric Castleman disease (MCD) and KSHV inflammatory cytokine syndrome (KICS). Existing research reveals that KSHV has developed numerous strategies to alter host cytokine signaling activities to facilitate viral persistence and escape host immune surveillance.

Despite three decades of research, there are still many questions in this field awaiting further investigation. This dissertation will investigate host cytokines as factors influencing the establishment of KSHV infection in the human tonsil. We have identified and characterized different cytokines …

Prg4/Cd44/Pp2a Signaling Axis: A Significant Regulator Of Gout Arthritis, Sandy Elsayed

Pharmaceutical Sciences (PhD) Dissertations

Introduction: Gout is a common chronic arthritis caused by monosodium urate (MSU) crystal deposition in joints leading to activation of synovial resident macrophages and downstream production of interleukin-1b (IL-1b). Xanthine oxidase (XO) catalyzes purines into uric acid (UA) and reactive oxygen species (ROS) that activate NLRP3 inflammasome. Protein phosphatase-2A (PP2A) may be involved in regulating inflammatory pathways in macrophages. Proteoglycan 4 (PRG4) and its receptor CD44 and its transducer PP2A signaling axis play a biologically significant role in regulating urate crystal inflammation.

Methods: Monocytes and macrophages were primed with TLR2 agonist and stimulated with MSU crystals. Fingolimod (PP2A …

Identifying A Glucocorticoid-Activated Gpcr That Rapidly And Non-Genomically Increases Camp Levels In Mammalian Cells, Francisco Nunez

Pharmaceutical Sciences (PhD) Dissertations

Glucocorticoids (GCs) are steroid hormones that regulate diverse physiological processes. Synthetic versions of GCs are commonly used to treat inflammatory diseases such as asthma by modulating gene expression to suppressing several inflammatory activities. However, it is estimated that 5-10% of asthmatics are unresponsive to GCs, which may be explained by receptor desensitization and/or the presence of a neutrophilic endotype. One understudied phenomenon of GCs is their ability to induce rapid, non-genomic actions. For example, GCs can acutely modulate calcium concentrations levels, induce smooth muscle relaxation and modulate nitric oxide synthase activity, within minutes and sometimes seconds, which is too rapid …

The Use Of Spectral Imaging To Reveal Inorganics And Organics Identity In The Biological Samples, Qamar Alshammari

Pharmaceutical Sciences (PhD) Dissertations

The wavelength is used to identify the exact location and quantify the number of molecules in the spectral imaging system. It aids in identifying materials and studying their quantities by examining how they interact with light. A traditional spectrometer provides spectrum information of chemical compounds, while standard imaging provides the intensity at each pixel of the image. Spectral imaging (SI) combines these two aspects by equipping intensity and spectral data for each pixel. In biomedical research, it is important to assess the inorganics/organics molecules to understand drug activity, cellular toxicity, and distribution. Using the microscopy technique, we found for the …

Kshv Susceptibility And Transmission Within Tonsillar Specimens, Farizeh Aalam

Pharmaceutical Sciences (PhD) Dissertations

Despite nearly three decades of research, not much is known regarding the early stages of development for KSHV lymphoproliferative disorders, hindering our ability to develop prophylactic measures or effective treatments. This dissertation will focus on the host and viral factors influencing the magnitude and dynamics of KSHV infection in the human tonsil to pave the way for future interventions directed at limiting person-to-person transmission of KSHV.

To understand the contribution of host factors to KSHV susceptibility in B lymphocytes, we generated a library of 40 tonsillar specimens. Our results indicate that the immunological composition of tonsillar lymphocytes varies across our …

Design, Synthesis, And Evaluation Of A Novel Cytotoxic Peptide-Doxorubicin Conjugate Targeting Triple-Negative Breast Cancer, Elmira Ziaei

Pharmaceutical Sciences (PhD) Dissertations

The aim of this thesis was to design, synthesize, and characterize a novel peptide-doxorubicin conjugate, evaluate in vitro stability and cytotoxicity properties of the conjugate and study its mechanism for uptake into the triple-negative breast cancer (TNBC) cells. For the synthesis of the conjugate, first, doxorubicin (Dox) was conjugated to a highly efficient established cross-linker, MCC, to give an intermediate product, MCC-Dox. MCC-Dox was characterized using NMR spectroscopy, mass spectrometry, and RP-HPLC and purified for subsequent reaction. Second, the 11-mer peptide 18-4 (NH₂-CWxEAAYQrFL-CONH₂) with high proteolytic stability and specificity for breast cancer cells was reacted with …

Viral Factors Influencing Early Infection Events During Ex-Vivo Kshv Infection, Ramina Nabiee

Pharmaceutical Sciences (PhD) Dissertations

The enigma of Kaposi Sarcoma Herpes Virus infection, and its persistence despite a quarter century of research on the virus, has given rise to an immediate need for addressing fundamental questions about basic immunology and virology knowledge regarding this virus. Kaposi Sarcoma Herpes Virus (KSHV), also known as Human Herpesvirus 8 (HHV8), is the etiological agent of Kaposi Sarcoma (KS) and other lymphoproliferative cancers, such as Multicentric Castleman’s Disease (MCD), Primary Effusion Lymphoma (PEL), and a newly discovered rare disease called KSHV Inflammatory Cytokines Syndrome (KICS). Epidemic KS, also known as AIDS-KS, is the most common cancer in untreated HIV …

The Roles Of Primary Cilia In Cardiovascular Diseases And Cancer, Maha Jamal

Pharmaceutical Sciences (PhD) Dissertations

Primary cilia are sensory organelles present in most mammalian cell types and regulate cell cycle and signaling pathways. Biochemical and molecular dysfunctions of primary cilia are associated with a wide range of diseases, including cancer, ciliopathies polycystic kidney disease (PKD, liver disorders, mental retardation, and obesity to cardiovascular diseases. Dysfunction in endothelial cilia contributes to aberrant fluid-sensing and results in vascular disorders, such as hypertension, aneurysm, and atherosclerosis. In this dissertation, the most recent outcomes on the roles of endothelial primary cilia within vascular biology have been summarized. Moreover, we evaluate the correlation between cilia formation or length and cell …