Medicine and Health Sciences Commons^™

Evaluation Of Spliceai For Improved Genetic Variant Classification In Inherited Ophthalmic Disease Genes, Melissa Reeves

Theses and Dissertations

ABSTRACT

EVALUATION OF SPLICEAI FOR IMPROVED GENETIC VARIANT CLASSIFICATION IN INHERITED OPHTHALMIC DISEASE GENES

By Melissa Jean Reeves, Ph.D.

A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University.

Virginia Commonwealth University, 2023

Major Director: Melissa Jamerson, PhD, MLS(ASCP)

Associate Professor, Department of Medical Laboratory Sciences

Inherited ophthalmic diseases impact individuals around the globe. Inherited retinal diseases (IRDs) are the leading cause of blindness in individuals aged 15 to 45. The personal, social, and economic impact of vision loss is profound. Due to individual differences, symptoms can be variable, and …

Protacs – A Novel And Rapidly Developing Field Of Targeted Protein Degradation, Hannah R. Gatley

Theses and Dissertations

There is a continued need for new technology and strategies for tackling cancer and other diseases, and within the current century a novel therapeutic strategy has emerged in the realm of targeted protein degradation called Proteolysis-Targeting Chimeras (PROTACs). This technology specifically targets and degrades disease-causing proteins via the ubiquitin-proteasome system, and has seen an explosion of research and intrigue in both academia and industry over the past two decades. The diversity of PROTAC classes based on the E3 ligase recruiting ligand and the target protein allows for a universal molecular structure that can be customized for a specific target and …

Interactions Between Hiv And Opioids On Antiretroviral Accumulation, The Blood Brain Barrier, And The Inflammatory Response In The Brain., Kara Rademeyer

Theses and Dissertations

The complex mechanisms related to HIV infection, neurodegeneration, and chronic neuroinflammation collectively describe neuroHIV (Hauser et al. 2007; Chang et al. 2014; Smith et al. 2014). Specifically, opioid abuse, poor penetration of antiretroviral (ARV) drugs, chronic inflammation and neuronal injury/degeneration are all implicated in neuroHIV (Fantuzzi et al. 2003; Letendre et al. 2004; Verani et al. 2005; Duncan and Sattentau 2011; Hong and Banks 2015; Simoes and Justino 2015; Olivier et al. 2018; Murphy et al. 2019; Osborne et al. 2020). For the first time, we demonstrate that morphine, fentanyl, and methadone in vivo alter the brain accumulation of ARVs, …

Probing The Porphyromonas Gingivalis Nitrosative Stress Response Network, Alexandra Galina

Theses and Dissertations

Objective: To persist in the oral cavity, the perio-pathogen Porphyromonas gingivalis must have an efficient nitrosative stress response mechanism. To better understand how P. gingivalis responds to nitrite (NO₂^-) we must determine what genes are involved in the nitrosative stress response network.

Methods: Through genomic screening, a list of genes was generated that were hypothesized to be part of the nitrosative stress response network and believed to be involved in nitrate/nitrite metabolism or redox state of the cells. Protein coding regions were replaced with the ermF sequence by allelic exchange mutagenesis. 15 mutants were created …

Characterizing The Effects Of Antiandrogens And Senolytics To Enhance The Therapeutic Response To Castration-Resistant Prostate Cancer, Justin M. Silverman

Theses and Dissertations

Prostate cancer is the most frequently diagnosed cancer in males and the second most common cause of cancer deaths. Androgen deprivation therapy, whether through surgical or chemical castration, is the mainstay for treatment of advanced prostate cancer; however, despite an initial response, most patients eventually develop a progressive PSA rise, and castration- sensitive prostate cancer gives rise to castration-resistant prostate cancer. The standard of care therapy includes the antiandrogens such as enzalutamide and abiraterone acetate as well as the microtubule poison, docetaxel, and various immunotherapies; however, while prostate cancer research is progressing, there continues to be a compelling need for …