Digital Commons Network^™

Exploring The Relationship Between The Epigenome And Metabolism In Mycn-Amplified Neuroblastoma, Krista M. Dalton

Theses and Dissertations

High risk neuroblastoma (NB) is responsible for nearly 15% of all cancer related deaths in the pediatric population. The transcription factor MYCN is the most studied oncogene in NB, automatically conferring high-risk and has been found to be difficult to target. One way that MYCN amplification in NB functions to support tumorigenicity is through altered metabolism, satisfying the demand for rapid proliferation by increasing the nutrient flux through biosynthetic pathways. We performed an unbiased screen on select metabolic targeted therapy combinations and correlated sensitivity with over 20 subsets of cancer. We found that MYCN-amplified NB is hypersensitive to the …

Advancing Social Equity And Promoting Black Self-Determination: A Community Garden Opportunity Plan For Richmond, Va, Alessandro U. Ragazzi

Master of Urban and Regional Planning Capstone Projects

Urban agriculture provides a variety of economic, environmental, and social benefits. Recognizing these benefits, the City of Richmond administers a community garden program known as “Richmond Grows Gardens.” Through this program, underutilized city properties are permitted for use as community gardens. However, an emerging concern is the potential for community gardens to perpetuate underlying structures of social and racial inequality through displacement and social exclusion. Considering these concerns, this plan investigates the implementation of community gardens in Richmond and establishes a methodology for ranking existing and available community garden sites based on the social and racial demographics of their surrounding …

A Three-Dimensional In Vitro Model Of Disease That Improves Preclinical Research By Incorporating Genetic Diversity And Increasing Physiological Accuracy, Akash Jagdeesh

Undergraduate Research Posters

Biomedical research is essential for the discovery of new medications and treatments, and is built upon the cooperation of preclinical (in vitro/vivo) research and clinical trials. However, 85% of treatments previously successful in vitro/vivo fail in clinical trials, suggesting that in vitro models are poor indicators of clinical success. The issue lies in conventional “two-dimensional” in vitro models containing genetically identical cells grown on a flat plate, which lack the variety of cell types and cooperation/structure found in real tissue. Moreover, 2D in vitro models do not simulate humans’ genotypic variability, which affects both …

Proposing An Rna Interference (Rnai)-Based Treatment For Human Immunodeficiency Virus (Hiv) By Analyzing The Post-Transcriptional Gene Targeting Of Sars-Cov-2, Hepatitis C Virus, And A549 Lung Cancer Cells, Arjun Jagdeesh

Undergraduate Research Posters

Human Immunodeficiency Virus (HIV) is a retrovirus that infects CD4+ T cell lymphocytes in humans, leading to the development of Acquired Immunodeficiency Syndrome (AIDS) if left untreated. While current treatment methods, including antiretroviral combination treatments, effectively limit HIV replication, HIV can evade these treatments due to its high mutation rate. Long-term antiretroviral treatment can also be toxic to patients, meaning patients would benefit from a new mechanism of HIV treatment. RNA interference (RNAi) is an antiviral pathway found in mammals, plants, and insects that involves a small-interfering RNA that is incorporated into a protein complex called the RNA-induced Silencing Complex …

Isoprenylation Inhibition Suppresses Fcεri-Mediated Mast Cell Function And Allergic Inflammation, Aditya Kotha, Jordan M. Dailey, Aslamuzzaman Kazi, Said Sebti, John J. Ryan

Undergraduate Research Posters

Allergic disease is driven by cell signaling cascades that activate immune cells. One key player is mast cells, which is activated by IgE antibodies signaling through the high affinity IgE receptor, FceRI. Therefore, targeting FceRI-mediated cascades can offer for novel treatments for allergic disease. Statins have been demonstrated to reduce the severity of asthma, a common allergic airway disease. Statins are an FDA approved class of drugs with the intended purpose of lowering blood cholesterol. We previously found that while statins inhibit mast cell function in allergic disease, these anti-inflammatory effects vary widely amongst differing mouse strains and human donors, …

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

Undergraduate Research 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 …

Gestational Vulnerability To Ozone Air Pollution - A Placental Story, Vishnupriya Alavala, Sarah Brent, Russell Hunter, Matthew J. Campen, Andrew Ottens

Undergraduate Research Posters

About 99% of the global population resides in areas with air pollution surpassing World Health Organization standards. Air pollution is associated with adverse neonatal health outcomes such as low fetal birth weight and an increased risk for maternal pre-eclampsia. A particularly reactive air pollutant is ozone, which forms reactive oxygen species that induce cellular damage. Research exists on the dispersion of reactive oxygen species through the bloodstream leading to fetal vulnerability during pregnancy, specifically via the placenta. Yet, placental and fetal development is a temporal process with varied susceptibility to negative gestational outcomes.

To addressing this gap, our laboratory utilized …

Structural Analysis Of Predicted Proteins Using Alphafold, Brydon P. Wall

Undergraduate Research Posters

The function of around 67% of predicted proteins from genes in Mycobacteriophage CheetoDust can not be confidently predicted using traditional techniques and can only be functionally labeled “hypothetical proteins”. However, a new approach using AlphaFold, an artificial intelligence tool to generate a structural prediction from a sequence, can take advantage of structurally conserved regions that were previously obfuscated to gain new insights and visualize data in new ways.

Since amino acid sequences are more conserved than its corresponding DNA sequence, amino acid sequences are used when predicting the function of the corresponding translated protein. Until recently, predicting structure from an …

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

Undergraduate Research 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 …

Investigation Of The Dyrk1a Regulation By Lzts2-Sipa1l1 Complex, Rebecca Gunnin, Austin Witt B.S., Larisa Litovchick M.D.,Ph.D.

Undergraduate Research Posters

A region on chromosome 21, the Down Syndrome critical region (DSCR), is associated with major defects found in Down Syndrome, such as craniofacial malformations. DYRK1A is a gene found on chromosome 21 within the DSCR that encodes an enzyme, dual specificity tyrosine-phosphorylation-regulated kinase 1A. DYRK1A is known to phosphorylate many substrate proteins and is thought to be involved in tumor suppression, neurological development, cell cycle regulation, and aging. Recently, the Litovchick lab and others reported that DYRK1A also plays a role in the double-strand break repair of DNA, which could lead to mutations and tumorigenesis, if deregulated.

The Litovchick lab …

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

Undergraduate Research 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

Undergraduate Research 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 …

Molecular Target And Circuitry Underlying The Preclinical Effects Of Psychedelics In Models Of Opioid Use Disorder, Alaina M. Jaster

Theses and Dissertations

Opioid use disorder (OUD), like other substance use disorders (SUD), is characterized by maladaptive behavioral allocation away from other rewarding aspects of life following prolonged use, as well as large rates of relapse. While pharmacotherapies exist for OUD, they tend to only target the opioid receptors rather than the underlying mechanisms behind the maladaptive behaviors. Serotonin (5-hydroxytryptamine; 5-HT) is involved in modulation of cravings and regulation of motivational reward-related behaviors, thought to be due to a top-down processing method of external and internal stimuli. Serotonin 2A receptors (5-HT_2AR) are widespread throughout the brain and most densely populate layer …

The Age And Primary Reason For The First Dental Visit In Children With Special Health Care Needs, Amanda Dickerson

Theses and Dissertations

Purpose: The aim of this project is to evaluate the average age and primary reason for the first dental visit among patients with special health care needs as well as to examine socioeconomic factors and other barriers related to children with special health care needs accessing care.

Methods: This is a cross-sectional survey that was distributed to caregivers of children with special health care needs. Study data was collected through REDCap, a secure web-based survey application. The inclusion criteria for participating in the survey included having a child with a special health care need that presented for a recall or …

Dental Treatment Planning: Decisions With Interdisciplinary Cases, William W. Porzio

Theses and Dissertations

Purpose: To explore the variance in treatment planning options with interdisciplinary cases that involve a combination of endodontic, periodontic, and prosthodontic factors.

Methods: A REDCap survey was emailed to Virginia based American Academy of Periodontology (AAP) members, American College of Prosthodontists (ACP) members, and periodontal residents to assessing various treatment planning options for six interdisciplinary cases.

Results: A total of 56 individuals responded to the survey; 10 periodontal residents, 35 practicing periodontists, 11 practicing prosthodontists. Response rate was not able to be evaluated based on the fact that third-party organizations were used to disseminate the survey in …

Histone Acetylation In Periodontal Diseases, Sarang Saadat

Theses and Dissertations

Background: Emerging data has indicated the significant role of epigenetic control in inflammation. Acetylation of lysine residues on histones is a major epigenetic modification of chromatin, which is required for cytokine gene expression and regulated in inflammatory diseases. It has been shown that periodontal bacteria induce histone acetylation in oral epithelial cells and experimental periodontitis in rodents. In this study, we investigated the acetylation level of histone 3 (H3) in gingival tissue from healthy and periodontitis patients. We hypothesize that cytokine over-production in periodontitis is associated with the hyper acetylation of histones. Methods: Periodontitis and healthy subjects who need periodontal …

The Wound Healing And Antibacterial Properties Of Mesenchymal Stromal Cell Extracellular Matrix Nanoparticles, Emily N. Wandling

Theses and Dissertations

Treatments for acute respiratory distress syndrome (ARDS) are still unavailable and the prevalence of the disease has only increased due to the Covid-19 pandemic. Mechanical ventilation regiments are still utilized to support declining lung function, but they also contribute to lung damage and increase the risk of bacterial infection. The anti-inflammatory and pro-regenerative abilities of mesenchymal stromal cells (MSCs) have shown to be a promising therapy for ARDS. We propose to utilize the regenerative effects of MSC secretome and the extracellular matrix (ECM) into a nanoparticle. Our mouse MSC (MMSC) ECM nanoparticles were characterized using size, zeta-potential, and mass spectrometry …

Combining Novel Direction Modulated Brachytherapy Tandem-And-Ovoids Applicators For Treatment Planning Of Multi-Institutional Cervical Cancer Cases: Removing Needles In Intracavitary-Interstitial Techniques, Sharmin Alam

Theses and Dissertations

Lack of standard guidelines for optimal needle insertion during high-dose-rate (HDR) intracavitary-interstitial (IC-IS) brachytherapy of the cervix means a sophisticated and technical skillset of inserting needles next to IC applicators must be developed to enhance plan quality. This study sought to evaluate the performance of two separate direction modulated brachytherapy (DMBT) tandem applicators used in conjunction with one set of novel DMBT ovoids, to effectively obviate the need for IS needles.

A cohort of 32 retrospective clinical HDR brachytherapy plans was re-planned with Varian’s BrachyVision^® treatment planning system, using VEGO^® inverse optimization algorithm, with dose heterogeneity accounted for …

Dune Building Dynamics Impact Cross-Island Connectivity And Barrier Island Characteristics, Alexander Sabo

Theses and Dissertations

Located at the land-sea interface, barrier islands are important protective features that reduce wave energy and erosion from mainland areas. Further, barrier islands provide habitat for many different organisms and serve as popular areas for recreation and tourism. As sandy landforms, barrier islands are easily disturbed, but often recover after disturbance as a result of island plant communities, specifically dune building grasses. Disturbance on barrier islands is driven by storms, tides, and overwash events. After disturbance has occurred, dune grasses colonize the dunes allowing for dune building and habitat restoration. On the Virginia barrier islands, there are three dominant dune …

Pre-Clinical Trials With Precision-Medicine Based Therapeutics In Basal-Like Patient-Derived Xenografts, David C. Boyd

Theses and Dissertations

Breast cancer treatments have improved over time, but the diseases seeing the most benefit from these improvements have the estrogen receptor, progesterone receptor, or are positive for HER2. Basal-like breast cancer tends to not have these biomarkers, which necessitates their treatment to be traditional, untargeted therapeutics which are less effective and tend to have harsh adverse effect profiles – this is an important unmet need. These studies utilize a variety of techniques, including tissue culture, viability assays, high-throughput screening, in vivo drug treatments and imaging, pathway analyses, molecular techniques such as Western blot, antibody arrays, RNA sequencing, sc RNA sequencing, …

The Type Iv Pilus Secretin Bfpb: Structural Analysis And Binding Interactions, Janay I. Little

Theses and Dissertations

Enteropathogenic Escherichia coli (EPEC) causes severe diarrhea in young children. The type IV pilus (T4P) of EPEC, known as the bundle-forming pilus (BFP), plays an important role in EPEC pathogenesis. T4Ps are a family of surface appendages that are important for adhesion, colonization, biofilm formation, virulence, twitching motility and many other functions. One essential component of the BFP system is the secretin, BfpB. Secretins are a large family of integral outer membrane proteins found in T4Ps as well as type II and type III secretion systems, and filamentous phages. Details of the secretin structure have been limited to the overall …

Pms And Gas Pollutants Removal By Electret Filter Media And Metal-Organic Frameworks (Mofs), Yu Zhang

Theses and Dissertations

Indoor air quality (IAQ) has been becoming a major concern worldwide because statistical data showed that the indoor concentrations of gas pollutants, e.g., volatile organic compounds (VOCs) and particulate matters (PMs) are often 2–5 times higher than that of outdoors. Especially, people spend 87% of their time indoors and increasing to more than 90% during COVID-19 pandemic. The high concentration of these indoor air pollutants is mainly due to the reduced air exchange rate for the design of energy-efficient building construction and the increased usage of furnishings, glues, paints, furnaces, etc., leading to VOC outgassing and particle emission. Evidence has …

Patterns, Mechanisms, And Characterization Of Carbon Cycling Stability Following Partial Forest Disturbance, Kayla C. Mathes

Theses and Dissertations

Among the most essential questions in the era of climate change is how the forest carbon (C) cycle will respond to an increase in the extent of biotic disturbances from insects and pathogens. While research has focused on stand-replacing disturbance regimes, less is known about C cycling stability following partial disturbances that produce gradients of disturbance severity. Belowground C cycling responses to disturbance are especially poorly understood, even though temperate forest soils contain up to 50% of total ecosystem C and soil respiration (R_s) accounts for more than half of temperate forest C loss. Interpreting trends and mechanisms …

Intrinsic Efficacy As A Determinant Of Opioid Effectiveness In Treatment Of Pain-Depressed Behavior, Edna Santos

Theses and Dissertations

Pain is a major public health concern that is commonly associated with behavioral depression, and a major goal in pain treatment is alleviation of pain-related behavioral depression. High-efficacy mu opioid receptor (MOR) agonists (e.g. fentanyl, morphine, oxycodone) are effective to treat pain, but their use is limited by side effects that not only endanger the patient but may also obscure analgesic rescue of pain-depressed behavior. The ongoing epidemic of opioid abuse and overdose deaths has stimulated research to discover non-opioid alternative analgesics; however, this search neglects the clinical potential of safer intermediate-efficacy MOR agonists (e.g. buprenorphine). The objective of the …

X-Ray Crystallography: A Tool For Understanding Protein Function And Drug Discovery, Akua K. Donkor

Theses and Dissertations

Structural biology has become an indispensable tool for determining the 3D structures of proteins for a comprehensive understanding of their functions on molecular level, and for elucidating binding cavities that can be targeted for structure-based drug discovery. X-ray crystallography, the most widely used structural biology technique was utilized in addition to other techniques to: (1) understand the role of pyridoxal reductase (PDXI) in pyridoxal 5’-phosphate (PLP) homeostasis; (2) Determine whether the putative PLP binding protein, YggS, is involved in PLP homeostasis; (3) Elucidate the molecular basis underlying Agrobacterium receptor VirA pathogenesis; and (4) Elucidate the structural basis of aromatic aldehydes …

Family-Based Support As Social Determinants Of Health Protective Factor On Depression Of Parents Of Children With Autism Spectrum Disorder, Bisola E. Duyile

Theses and Dissertations

All parents experience challenges in their caregiving roles (Barańczuk & Pisula, 2020). However, parents raising a child/children with disabilities experience different social barriers (Oliver, 1996) that may also contribute to additional stressors in their caregiving role (Tomeny, 2016). Although these parents, on average, have reported greater symptoms of depression than parents of typically developing children, research shows that parents who reported receiving social support had lower symptoms of depression and stress (Das et al., 2017; Singh et al., 2017). Through the social determinants of health (SDOH) framework (ODPHP, 2022), the present study investigated informal/family-based support and its protective impact on …

Investigating The Dynamics And Fragmentation Of Nitroaromatic Radical Cations Through Femtosecond Time-Resolved Mass Spectrometry And Computational Chemistry, Hugo Andres Lopez Pena

Theses and Dissertations

Chemists have sought to control molecular dissociation with lasers for decades. Effective control of unimolecular dissociation was only achieved with the development of high-intensity ultrashort pulsed lasers and coherent control techniques that operate on timescales faster than vibrational energy redistribution. In view of this, our lab has specialized in the study of polyatomic radical cations using femtosecond time-resolved mass spectrometry (FTRMS). The interest in radical cations stems from the fact that they are highly reactive species that contribute to many physical, chemical, and biological processes. For instance, radical cations participate in shock initiation of detonated energetic materials used as explosives …

Asymmetric Cuh-Catalyzed Reductive Coupling Of Allenamides With Carbonyl Electrophiles & Development Of Nanocatalysts For Heterogeneously Catalyzed Buchwald-Hartwig Amination, Raphael K. Klake

Theses and Dissertations

Many drugs and natural products contain multiple stereogenic carbons bearing heteroatoms throughout their carbon framework. Therefore, methods that can efficiently install multiple heteroatoms on a molecule are valuable. Reductive coupling reactions have been extensively studied, and the allylation of carbonyls via the reductive coupling approach has been a key method for generating chiral tertiary and secondary allylic alcohols. This work utilizes inexpensive Cu for the asymmetric reductive coupling of allenamides with carbonyls to simultaneously install two heteroatoms (oxygen and nitrogen) on the product. These molecules have a polarity profile that make them difficult to make using traditional methods. Herein, we …

Addressing Death Distress In Caregivers Of Patients With Malignant Glioma, Kelcie D. Willis

Theses and Dissertations

The field of psychosocial oncology seeks to improve the quality of life of patients and families affected by cancer. This task becomes increasingly important when there are limited, non-curative treatment options, a high probability of recurrence, and rapid functional decline, such as in the case of a malignant glioma (MG). Indeed, the diagnosis of a MG is associated with negative sequalae that often translates to higher caregiver burden. Caregivers—who must manage the functional decline of the patient, changes within the family, and a complicated medical system—often feel overwhelmed, isolated, and ill-equipped to handle these myriad responsibilities. While they also report …

Quantitative Changes In Hippocampal Ccr5+ Microglia With The Administration Of Maraviroc (Mvc): Does Sex Matter?, Ama S. Boakye-Agyei

Theses and Dissertations

Human immunodeficiency virus type-1 (HIV-1) has been greatly studied in recent decades. Combined anti-retroviral therapy (cART), the development of drug treatments such as maraviroc, and the wider availability of support for those in resource-rich environments have been instrumental in improving the prospects of people living with HIV (PLWH). It is well- documented that PLWH can suffer from a host of cognitive deficits collectively known as HIV- associated neurocognitive disorders (HAND). Moreover, the role of biological sex in the development of HAND and other cognitive deficits is still being studied. C-C chemokine receptor type 5 (CCR5) is one of the two …