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The Regulation of Ceramide Generation and Its Downstream Metabolites as Targets for Cancer Therapy
No full textSphingolipids, a class of bioactive lipid signaling molecules, have been shown to play vital roles in cancer and other human diseases. The central sphingolipid molecule, ceramide, is known to play primarily growth-inhibitory roles in tumors, while its downstream metabolites, such as sphingomyelin, glycosphingolipids, and sphingosine-1-phosphate, are known to play growth-promoting roles. Their metabolism, then, plays a pivotal role in tumor progression and metastasis. Although much work has been done in understanding the mechanistic underpinnings of sphingolipid metabolism in cancer, the various ways in which ceramide and its downstream metabolites control tumor growth remain elusive. The works presented here reveal novel regulatory mechanisms of sphingolipid generation as well as the biological consequences of dysregulated sphingolipid metabolism.
The first chapter provides an overview of sphingolipid metabolism as well as the established roles of sphingolipids in human health and disease. The second chapter investigates the role of post-translational modifications on ceramide synthase 6 (CerS6) activity in HCT116 colon cancer cells. The data presented demonstrates that glycosylation of CerS6 at N18 is essential for its activity, and ablated glycosylation results in modulation of cellular signaling pathways. Work presented in the third chapter shows a novel role for glycosphingolipids in lysosomal turnover and autophagy, and proposes a mechanism by which glucosylceramide synthase (GCS) inhibition induces tumor cell death in colon, cervical, and ovarian cancers. Further, these data provide critical mechanistic insights into the use of the GCS inhibitor, eliglustat, in combination with immunotherapies in cancer patients. The fourth chapter provides preliminary characterizations of subcellular pools of sphingolipids using mitochondrial and lysosomal rapid-immunoprecipitation and LC/MS-MS lipidomics analysis in HCT116 colon cancer cells. These results serve as a proof-of-concept for the use of rapid-immunoprecipitation in studying the regulation and biological impacts of subcellular pools of sphingolipids species. The final chapter offers analysis of the data presented and future directions.
Together, the work presented in this dissertation shows novel regulatory mechanisms of sphingolipid generation, and the biological consequences of sphingolipid dysregulation. These mechanistic insights may be critical for developing novel chemotherapeutics to be used for the treatment of patients suffering from various cancers
Examination of Caregiver Knowledge, Attitudes, and Practice (KAP) Concerning Consumption of Omega-3 in Youth with Sickle Cell Disease
No full textSickle cell disease (SCD) is the most common genetic blood disorder in the US. Inflammatory processes trigger and maintain pain (acute and chronic) and lead to multi-system complications. Randomized controlled trials have indicated that omega-3, a healthy dietary fatty acid, reduces pain frequency and inflammation in youth with SCD. Despite evidence of it as a promising complementary pediatric SCD pain treatment, there is limited information on omega-3 consumption knowledge among caregivers of youth with SCD, and rates of consumption among youth with SCD. The current study examined caregiver knowledge of and attitudes toward SCD-related omega-3 benefits, and consumption among youth with SCD. Caregivers (N = 57, M age = 38.65) of youth (aged 5-17) with SCD were recruited from VCU’s Pediatric SCD clinic. Participants completed surveys via REDCap on demographics; SCD Omega-3 Knowledge, Attitudes and Practice (K.A.P.); and pain. Overall K.A.P. scores were low. Approximately 80% of caregivers reported they had not heard of omega-3 as a complementary pain treatment option. While overall attitudes were low, caregivers reported low perceived barriers and high perceived severity and self-efficacy, all indicative of positive attitudes. Youth consumption was significantly predicted by caregiver knowledge (β = .92, t = 2.88) and perceived barriers (β = -.57, t = -2.43, p = .02). The findings highlighted the lack of awareness of omega-3 benefits among caregivers of youth with SCD. These findings indicate a need for dissemination efforts to raise awareness of omega-3 as an evidence-based complementary treatment option for pediatric SCD pain
Wondering and Wandering
Get PDFFor my thesis, I have taken the concept of excavation and used it as a visual metaphor for my artistic process. Using my recurring motifs of a hole, ladder, and the gem, I break down the writing into three sections. First, the hole, a metaphor for entering an image; second, the ladder, process as investigation; and lastly, the gem, which represents wonder and delight. This work is influenced by childhood fantasies, video games, and believing in magic
Acer rubrum: Descending towards forest dominance
Get PDFAcer rubrum, more commonly known as the red maple, is a hardwood, late successional species of tree commonly planted for its deciduous nature and vibrant coloring of its leaves in the beginning of autumn (Abrams, 1998). The species is very tolerant of varying light and soil moisture levels and often dominates sub and mid-canopy levels of hardwood forests (Missouri Botanical Gardens). It was hypothesized that as the I moved from an upland location to a lowland location near a wetland that the A. rubrum trees would be more productive and have a greater above ground biomass. This was not supported by the data collected and a T-test comparing average percent slope and above ground biomass (p = 0.0002949) indicated that these results were significant. An inverse relationship between the two variables suggested that A. rubrum was more productive in drier, upland regions compared to the moist soils closer to the wetland. These results, while significant, did not have the best representation of the sample due to the varying number of trees in each transect region.https://scholarscompass.vcu.edu/uresposters/1484/thumbnail.jp
DEVELOPMENT OF NOVEL CHIMERIC EPITOPE-BASED DIAGNOSTIC ANTIGENS FOR EHRLICHIOSIS AND ANAPLASMOSIS
No full textEhrlichiosis and anaplasmosis are increasingly prevalent tick-borne diseases with limitations in current diagnostic methods. This study aimed to develop novel chimeric epitope-based diagnostic antigens with enhanced sensitivity and specificity for detecting Ehrlichia and Anaplasma infection in canines. Potential diagnostic antigens were identified using immunoprecipitation followed by liquid chromatography-mass spectrometry (IP-LC/MS). Chimeric diagnostic constructs were designed incorporating epitopes from identified antigens, epitope localization studies and bioinformatic predictions aided in the selection of antigenic regions. Constructs were evaluated using indirect enzyme-linked immunosorbent assays (ELISA) against well-characterized canine serum panels, including naturally and experimentally infected samples. The results demonstrated the successful development of EDC4, which exhibited 98.46% sensitivity and 96.83% specificity for detecting Ehrlichia spp., including enhanced detection of E. ewingii. Furthermore, ADC1 showed 100% sensitivity and 98% specificity for detecting A. phagocytophilum and A. platys. These novel chimeric constructs outperformed commercially available diagnostic tests, such as SNAP4DX Plus. Future directions include expanding serum panels, investigating additional antigens, conducting time-course infection studies, and exploring the potential for a multiplex assay. This research highlights the potential of chimeric epitope-based antigens for improving the accuracy and breadth of diagnostics for canine ehrlichiosis and anaplasmosis
How to Remain a Stranger / Encountering, in a Basement
Get PDFHow to Remain a Stranger / Encountering, in a Basement consists of two parallel essays. On the lefthand side of the page, How to Remain a Stranger explores the ways that the legend of the Wandering Jew, the Tradescantia genus of plants, peddlers, and exile relate to my practice of collecting, sorting, and combining found objects. On the righthand side, Encountering, in a Basement describes my thesis exhibition at the Institute for Contemporary Art at Virginia Commonwealth University. Focusing on the idea of the encounter, I detail the materials, considerations, and processes behind four of the ten sculptures in the show. Together, the two texts meander, mimicking the movement of objects and the paths I take as I encounter them in the world
A Call To Action For Transport Justice: Exploring Transportation Disadvantages Faced By Justice-Impacted Individuals Reintegrating Into Rural Communities
Get PDFThis study explores the intersection of rural reentry and transportation planning, emphasizing the importance of Transport Justice in overcoming barriers faced by transit-dependent populations, particularly formerly incarcerated individuals. While urban transportation planning is widely discussed, this research highlights the overlooked challenges that rural environments pose for individuals reentering society. Through a multi-method approach that involved document analysis, participant observations, and informal discussions, this study uncovers a range of themes related to accessibility, reliability, vulnerability, and the quality of commuting experiences. The findings underline the necessity for transparency, accountability, and collaboration across sectors to address these gaps and inform policies that promote transportation equity. This study further highlights the importance of interdisciplinary partnerships involving urban planning, criminal justice, and social work to ensure that marginalized populations can successfully reintegrate into society. Ultimately, this research affirms that Transport Justice, a framework for equitable transportation, remains at a distant goal for rural reentry landscapes, underscoring the need for systemic change in both infrastructure and policy to bridge longstanding disparities
Senior Recital, Arianna Greggs, violin, video
Get PDFSenior recital videoArianna Greggs, violinDaniel Stipe, pianoMagdalena Adamek, pianoMonday, April 28, 2025 at 4:00 p.m.W.E. Singleton Center for the Performing Arts922 Park Avenue | Richmond, VirginiaThe presentation of this senior recital will fulfill in part the requirements for the Bachelor of Music degree in Performance. Arianna Greggs studies violin with Prof. Susanna Klein
HEALTH AFTER RESETTLEMENT: PREDICTORS OF PRIMARY CARE UTILIZATION AMONG SOMALI REFUGEES LIVING WITH CHRONIC ILLNESS
No full textAs the leading cause of death globally, chronic conditions have come under major focus in recent years, with refugees–particularly from Africa–confronting documented disparities in disease burdens and premature deaths. Health service utilization (HSU) is cited as an effective point of intervention for both mitigating complications arising from chronic illnesses and alleviating related health disparities. While the decision and ability to utilize health services are complex, self-assessed health status consistently emerges as a powerful predictor. Evaluation of key contextual factors associated with health status and primary care utilization can support migrant wellbeing. Adopting an integrative model merging Andersen’s Expanded Behavioral Model, the Basic Behavioral Epidemiological Model, and the Immigrant Health Service Utilization Framework, within a broader socio-ecological perspective, this study utilizes a cross-sectional, structured survey design to examine health status and HSU among Somali migrants living in the U.S (n=165). Given the complexity of migrant health experiences, a multifactorial and ecological analysis of the drivers of health status and service use is essential. The purpose of this dissertation study is to: (a) identify the predisposing, enabling, and need factors at both the contextual and individual levels that are associated with HSU among Somali refugees with chronic conditions, and (b) explore the effects of pre and post migration stress on HSU for this population. Findings revealed that insurance coverage and health status are the strongest direct predictors of health service use, with individuals who were insured and those reporting moderate health status more likely to access care. Additionally, participants who perceived elevated levels of illness within their ethnic community were less likely to seek care, suggesting that perceived normalization of illness may discourage care-seeking behavior. While post-migration stress did not directly predict healthcare utilization, it significantly increased unmet healthcare needs, which in turn were associated with lower utilization. Finally, state of residence was a significant moderator in the relationship between post-migration stress and unmet healthcare needs, suggesting geographic differences in experiences with post-migration stress and healthcare access. The results from this dissertation study underscore the importance of considering the health effects from forced displacement, community-level perceptions, and contextual disparities—such as state-specific differences—in shaping the health experiences of Somali refugees with chronic conditions
Elements of a Talent Information System for the Shenandoah Valley Partnership
Get PDFThis study examines the development of a comprehensive talent information system for the Shenandoah Valley Partnership (SVP), addressing the region’s prioritized need for talent attraction and retention. Through a mixed-methods approach combining literature review, demographic analysis, and qualitative interviews with comparable regional economic development organizations, the research identifies effective strategies for collecting, managing, and analyzing workforce data. The Shenandoah Valley region, comprising twelve localities in Virginia, faces challenges in educational attainment and healthcare provision despite possessing significant natural and cultural assets. Findings reveal three key components for effective talent information systems: (1) ambassador programs that provide qualitative insights on regional attraction factors, (2) structured data collection from departing and potential talent to understand migration motivations, and (3) comprehensive inventories of quality-of-life amenities that differentiate the region. The research indicates that successful talent information systems balance sophisticated data needs with practical implementation constraints, often utilizing accessible public data sources rather than exclusively relying on costly proprietary databases. Based on these findings, the study recommends a three-goal implementation strategy: enhancing SVP’s ambassador program to collect richer qualitative data, establishing systematic approaches to understanding talent outflow, and leveraging collected data to highlight regional strengths. This framework offers a replicable model for rural and small metropolitan regions seeking to enhance talent attraction efforts through evidence-based approaches that align with organizational capacity constraints