Life Sciences Commons^™

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 …

Stage-Structured Predator-Prey Interactions In A Warming World: A Case Study In Riverine Rock Pools, Andrew T. Davidson

Theses and Dissertations

Warming can impact predator-prey interactions through a variety of mechanisms. For example, warming can both alter the rate at which predators consume prey and the rate prey develop through vulnerable life stages. Thus, the overall effect of warming on consumer-resource interactions will depend upon the strength and asymmetry of warming effects on predator and prey performance. Here, we describe the consequences of these asymmetrical responses to temperature by first developing a simple stage-structured modeling framework, then applying that framework to predation of American rock pool mosquito larvae, Aedes atropalpus, by several common predators in riverine rock pools. We then …

Integrative Post-Gwas Analyses Of Psychiatric Disorders: Identifying Putative Risk Genes And Gene Sets Using Transcriptome, Proteome And Methylome Information, Huseyin Gedik

Theses and Dissertations

Genome-wide association studies (GWAS) of psychiatric disorders (PD) yield numerous loci with significant signals, but often they do not implicate specific protein coding genes. Because GWAS risk loci are enriched in expression/protein/methylation quantitative loci (e/p/mQTL, hereafter xQTL), transcriptome/proteome/methylome-wide association studies (T/P/MWAS, hereafter XWAS), which integrate information from GWAS and x-level (mRNA, protein or DNA methylation levels) coming from largest xQTL studies, can link GWAS signals to effects on specific genes. For gene level analyses, researchers use mendelian randomization (MR) methods to fine-map the association between x-levels and trait. However, none of the previous studies ever jointly analyzed XWAS of multiple …

Association Of Interpersonal Trauma And Polygenic Risk Scores With Depressive Symptoms In College Students, Rowan K. O'Hara

Theses and Dissertations

Major depression is considered a complex trait influenced by both polygenic risk factors and environmental exposures, such as childhood trauma. This study applied statistical genetic methods to calculate aggregate genetic risk for major depression to predict depressive symptoms scores in a college student sample. Data were from the Spit for Science (S4S) study in which college students from a large urban university self-reported interpersonal trauma (IPT) exposure prior to college and depressive symptoms from the past month (N = 7502; ancestry group: 20% African [AFR], 12% Admixed Americas [AMR], 10% East Asian [EAS], 49% European [EUR], 8% South Asian [SAS]). …

The Impact Of Hiv-1 Tat And Morphine On Spatial Distribution Of Drugs In The Brain., Austin M. Jones

Theses and Dissertations

Despite combination antiretroviral therapy effectively suppressing HIV within the periphery, the central nervous system (CNS) remains affected by the virus. Approximately half of people living with HIV will experience HIV-associated neurocognitive disorders (HAND) or neuroHIV. Concurrent opioid use exacerbates neuroHIV by promoting neuroinflammation, viral replication, and potentially altering the antiretroviral concentrations within the brain.

Using a transgenic mouse that expresses the HIV-1 Tat protein, we examined the effects of Tat and morphine on antiretroviral accumulation and distribution and the effects of Tat on morphine accumulation within the brain using infrared matrix-assisted laser desorption electrospray ionization with mass spectrometry imaging (IR-MALDESI-MSI). …

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 …

Genomic Comparison Of Dba/2j And C57bl/6j Strains Of Mus Musculus And Best Practice Of Genome Alignment For Bioinformatics Analyses, Dustin J. Zeliff

Theses and Dissertations

Alcohol use disorder is known to have significant genetic components that contribute to an individual’s susceptibility to the disease. Mouse models are commonly used to study the mechanisms underlying alcohol use disorder, with C57BL/6J (B6) and DBA/2J (D2) being two of the more prominently used inbred strains. Research in the Miles Laboratory has used these two strains, and genetic panels of mice derived from them, to identify potential genes associated with variance in ethanol-related behaviors using quantitative trait loci (QTL) analysis. For example, Ninein (Nin) was identified as a potential candidate gene for the anxiolytic effects of ethanol, discovered because …

Novel Strategies In Head And Neck Tumor Therapy; Contribution Of Senescence In Therapy Response, And Resistance Development After Cisplatin Treatment, Fereshteh Ahmadinejad

Theses and Dissertations

Therapeutic outcomes achieved in head and neck squamous cell carcinoma (HNSCC) patients by concurrent cisplatin-based chemoradiotherapy initially reflect both tumor regression and tumor stasis. However, local, and distant metastasis and disease relapse as well as cisplatin-induced resistance are common in HNSCC patients. In the current work, we demonstrate that cisplatin treatment induces senescence in both p53 wild- type HN30 and p53 mutant HN12 head and neck cancer models. We also show that tumor cells can escape from senescence both in vitro and in vivo. We further established a cisplatin-resistant cell line from HN30 parental cell line that underwent brief senescence …

A Standardized Pipeline For Isolation And Assembly Of Genomes From Symbiotic Bacteria In Whole Louse Genomic Sequence Data., Mohammad Mikail I. Bala

Theses and Dissertations

Many insects are known to harbour intracellular and heritable bacteria (endosymbionts), which provide their hosts with adaptive traits. Whole insect gDNA shotgun sequencing projects often sequence the genome of endosymbiont, in addition to the insect’s genome. There are approximately 600 whole genome shotgun libraries from insects available on the public repository (NCBI), which can be mined to obtain endosymbiont genomes. The assembly and annotation of endosymbiont genomes can contribute towards the exploration of their role as obligate symbiotic partners. However, de novo assembly of an endosymbiont genome, continues to be challenging, when the host and/or enteric bacterial gDNA is present …

Salinization Impacts On Heterotrophic Respiration, Ecosystem Respiration, And Plant Productivity In Tidal Freshwater Marshes, Kelsie J. Moses

Theses and Dissertations

Tidal freshwater marshes have preserved substantial stocks of soil carbon, which represents carbon dioxide that is no longer in the atmosphere. There is conflicting evidence in the literature about how disturbances such as sea level rise and associated wetland salinization impact the accumulation and long-term stability of this stored carbon. The goal of this experiment was to quantify how salinization impacts total ecosystem respiration and its component parts, autotrophic and heterotrophic respiration. This was a microcosm experiment using a C4 plant (Spartina cynosuroides) grown in soil derived from C3 plant matter and exposed to different salinities (0 to …

Examining Genetically-Informed Etiologic Models Of Co-Occurring Posttraumatic Stress Disorder And Recreational Cannabis Use Among College Students, Terrell A. Hicks

Theses and Dissertations

The college years encompass a period of increased risk recreational cannabis use (RCU), as well as a time of increased risk for trauma exposure and developing posttraumatic stress disorder (PTSD). Given the high co-occurrence between RCU and PTSD, and the potentially negative consequences of the two (e.g., worse academic outcomes), there is a need to understand the etiologic mechanisms of these commonly co-occurring conditions. Two primary phenotypic models exist: self-medication model (i.e., PTSD to RCU) and the high-risk model (i.e., RCU to PTSD). To date, there are two existing studies longitudinally examining the etiologic models proposed to explain co-occurring RCU …

Population Demography Of A Neotropical Migratory Songbird In The Face Of A Changing Climate, Adele Balmer

Theses and Dissertations

This dissertation investigates the population dynamics and demographic trends of the Prothonotary Warbler (Protonotaria citrea), a migratory songbird that breeds in North America during the spring and summer and overwinters in Central and northern South America. The primary objective of this dissertation is to examine the combined implications of variation in weather and individual traits on demographic traits and to project the effects of climate change on population trajectories of the Prothonotary Warbler.

The analyses conducted in this dissertation centered around female Prothonotary Warblers; however, visual identification of a nestling’s sex is impossible in most altricial bird species, …

Comparing The Microbiomes Of Dental Plaques In 19th Century Ancestral Remains, Ananya Udyaver

UROP Posters

During the construction of VCU’s Hermes A. Kontos Medical Sciences Building in April 1994, nineteenth century ancestral remains were found in an abandoned well on the Medical College of Virginia (MCV) campus. This well, now known as the East Marshall Street Well (EMSW), is thought to have been used as a disposal location for cadaver dissection for surgical and other medical waste in the past. VCU is now seeking to use DNA sequencing technology to match and assemble bones from each individual for a proper burial, uncover the cultural and historical context in which these people lived, and bring a …

Cellular Glycosphingolipid Imbalance Modulates Emt In Cancer Cells, Laura E. Clark, Amanda Dickinson, Santiago Lima

UROP Posters

Sphingolipids are key components of the plasma membrane and are regulators of complex biological processes often altered in cancer cells. In human tumors, genes of key enzymes that regulate levels of glucosylceramide and lactosylceramide are often amplified. However, it is unknown why these traits are positively selected in transformed cells. In this work, we used CRISPR-Cas9 to knockout two key enzymes amplified in tumors in HeLa and H1703 tumor-derived cell-lines. As expected, the knockout lines had dramatic accumulation of GlcCer and LacCer. However, unexpectedly, they showed significantly decreased in-vitro wound-healing capacity and an almost complete loss of in-vitro extra-cellular matrix …

Respire: A Technological Tool To Navigate Mechanical Ventilation In Patient Care And Educational Settings, Swara Chokshi

UROP Posters

Around the world, more than 20 million patients rely on mechanical ventilators annually; however, not enough individuals understand how to operate ventilators, posing a risk to the health of many. Moreover, it is increasingly difficult to determine optimal mechanical ventilator settings in a timely fashion, especially in low-resource countries and critical care areas. Respire is a mobile application that bridges this gap in a twofold manner: it is designed to assist healthcare workers around the world navigate and use mechanical ventilators effectively as well as educate the general public about mechanical ventilation. Respire offers a user-friendly yet educational interface that …

The Collaboration Between Art And Botany, Hee So, Sierra Beecher

UROP Posters

Using past research from my work study with Dr. Beecher where a team of students focused on quantitative and diagnostic anatomies of salt marsh and beach grasses on the Atlantic coasts, I used the research collected and created vector-based diagrams that were easily readable for Biology students at VCU. These illustrations were used in a manuscript we have been preparing, which has been accepted by the “Castanea” scientific journal. During the research fellowship, I was able to design a poster that portrayed the benefits of collaboration between art and botany, and Dr. Beecher presented the poster at the ASPB conference …

Glyphosate And Dopaminergic Neurotoxicity: Herbicide Impacts On Parkinson's Disease Development, Lojy Hozyen

UROP Posters

Nearly one million individuals in the United States are living with Parkinson’s disease (PD). In the past two decades, the death rate from PD has risen by about 63 percent in the United States. Major findings have been made in the past five years about the potential impact of glyphosate (N-(phosphonomethyl) glycine) exposure on the onset of PD symptoms. The purpose of this meta-analysis is to provide a compiled update on the chemical and biological alterations that glyphosate imposes on the human brain. A meta-analysis was conducted to create a quantitative estimate of the connection between PD and glyphosate. Findings …

Applications Of Urban Land Evaluation And Site Assessment (Ulesa) In Chesterfield County, Virginia, Emily Hastings

Theses and Dissertations

Urban and suburban agriculture is increasing in popularity across the United States. However, many of these farms are short-lived due to a combination of human factors (e.g., managerial, economic, cultural) and environmental or spatial factors (e.g., zoning, soil quality, distance to markets). Geospatial analysis, in the form of suitability modeling, could aid in locating suitable sites for these activities. Land Evaluation and Site Assessment (LESA) is a suitability modeling technique that generates a score for agricultural land use in traditionally rural spaces. This research explores adapting this method to encompass the complexities of placing diverse, in-ground agriculture in urban and …

Boxed Lunches, Lunch

Biology and Medicine Through Mathematics Conference

No abstract provided.

Mathematics Of A Single-Locus Model For Assessing The Impacts Of Pyrethroid Resistance And Temperature On Population Abundance Of Malaria Mosquitoes, Jemal Mohammed-Awel

Biology and Medicine Through Mathematics Conference

No abstract provided.

Mixed Mode Oscillations In Three-Timescale Coupled Morris-Lecar Neurons, Ngocanh Phan, Yangyang Wang

Biology and Medicine Through Mathematics Conference

No abstract provided.

Modeling The Cardiovascular Dynamics Of Postural Orthostatic Tachycardia Syndrome, Justen Geddes

Biology and Medicine Through Mathematics Conference

No abstract provided.

Modeling Acute And Chronic Vascular Adaptations To A Major Arterial Occlusion, Erin O. Zhao

Biology and Medicine Through Mathematics Conference

No abstract provided.

Mathematical Model Of Subthalamic Nucleus Neuron - Characteristic Activity Patterns And Bifurcation Analysis, Choongseok Park, Sungwoo Ahn, Leonid Rubchinsky

Biology and Medicine Through Mathematics Conference

No abstract provided.

Modeling The Dynamics Of Usutu Virus Infection In Birds, Nora G. Heitzman-Breen

Biology and Medicine Through Mathematics Conference

No abstract provided.

Universality And Synchronization In Complex Quadratic Networks (Cqns), Anca R. Radulescu, Danae Evans

Biology and Medicine Through Mathematics Conference

No abstract provided.

Epidemiological Assessment Of Wolbachia-Based Biocontrol For Reduction Of Dengue Morbidity, Olga Vasilieva, Oscar E. Escobar, Hector J. Martinez, Pierre-Alexandre Bliman, Yves Dumont

Biology and Medicine Through Mathematics Conference

No abstract provided.

Mechanical Parameters Fitting For Layer-Reduced Umbilical Arteries Used For Grafting, Kun Gou

Biology and Medicine Through Mathematics Conference

No abstract provided.

Mathematical Model Of Triple-Negative Breast Cancer In Response To Combination Chemotherapies, Angelica Davenport, Yun Lu, Carlos Gallegos, Adriana Massicano, Katherine Heinzman, Patrick Song, Anna Sorace, Nick Cogan

Biology and Medicine Through Mathematics Conference

No abstract provided.

Model Of Quarantine Implementation In An Animal Shelter For Canine Distemper Outbreak, Virginia Parkman, Nick Cogan

Biology and Medicine Through Mathematics Conference

No abstract provided.