UMB Digital Archive

Scholarship & History

The UMB Digital Archive is a service of the Health Sciences and Human Services Library (HS/HSL) that collects, preserves, and distributes the academic works of the University of Maryland, Baltimore. It is a place that digitally captures the historical record of the campus.

 

  • Tumor Microenvironmental and Cell-Intrinsic Mechanisms of Microtubule Stabilization in Breast Cancer

    Stemberger, Megan; Martin, Stuart S. (2024)
    Metastasis accounts for over 90% of breast cancer-associated mortality. Elucidating the pro-metastatic changes that occur within breast tumor cells and the surrounding tumor microenvironment (TME) is imperative for the development of antimetastatic therapies. This dissertation characterizes the effects of elevated H2O2 in the breast TME and cell-intrinsic alterations in the microtubule cytoskeleton for their impact on metastatic potential. H2O2 exposure induces -tubulin detyrosination and acetylation, two markers of poor patient prognosis, via a conserved Ca2+-dependent mechanotransduction pathway. H2O2 induces the formation of microtubule-based microtentacles (McTNs) which are enriched in detyrosinated-tubulin and acetylated-tubulin, but inhibits McTN-mediated functions of cell clustering and reattachment. This dissertation also elucidates the function of specific subsets of microtubules that have been post-translationally detyrosinated in breast cancer. Detyrosinated microtubules may provide an improved therapeutic target compared to current microtubule-stabilizing agents, which indiscriminately target all microtubules and are associated with broad side effects and inadvertently increase metastasis. Leveraging the recent discovery of the tubulin carboxypeptidase (TCP) enzyme, this study demonstrates the feasibility and functionality of lentiviral-based, constitutive TCP overexpression in mammary epithelial cells. TCP overexpression increases detyrosinated-tubulin, which is accompanied by morphological changes and enhanced cellular reattachment and migration. Collectively, this dissertation establishes that H2O2 signals in the TME induce microtubule stabilization and affect metastatic phenotypes, and provides the tools and preliminary data to continue investigating the therapeutic potential of targeting -tubulin detyrosination to reduce breast cancer metastasis.
  • Characterizing HIV-1 Genome Dimerization

    Yasin, Saif; Summer, Michael F. (2024)
    Like nearly all retroviruses, HIV-1 selectively packages two copies of its full-length genome after the formation of a dimer – a process essential not only to packaging but also reverse transcription and recombination. The dimerization process has been found to be mediated by the untranslated region of the HIV-1 transcript, the 5′-Leader, a nearly 400 nucleotide region of the RNA genome that is found to be responsible for regulating RNA fate and function. Structural methods on large RNAs like the dimeric leader (~800 nts) are notoriously limited due to the their inherent flexibility and size; however, more recent methodologies within the Summers lab have allowed us to characterize secondary structure domains within the intact leader. Using these defined structures, we can analyze how different domains of the leader influence RNA function and affect the viral life cycle. The goal of this thesis is to characterize the HIV-1 genomic dimer. We specifically looked at different domains and how they regulate dimerization and subsequent functional processes. We were specifically able to study the function of the 5′-polyadenylation signal, protein coding sequence downstream of the leader, the dimerization initiation site, and the major splice donor. We aimed to characterize processes such as dimerization, packaging, and even translation. Our work also sought to answer a long-standing question about the HIV-1 retroviral lifecycle: how could a single RNA transcript produce protein and also serve as the viral genome? We believe the process relies on the production of two different transcripts with different start sites, which modulate dimerization, but more importantly the structure at the 5′-cap which seems to subsequently dictate RNA fate. Overall, this work highlights the dynamic nature of RNA processes and how small changes in sequence can lead to dramatic changes in the HIV-1 lifecycle. We show that the role of dimerization within the HIV lifecycle is misunderstood, and still requires further characterization to understand how this structure dictates all its necessary functions. Our hope is that understanding the RNA processes involved in HIV-1 replication will allow the development of new therapeutic targets for treatment of the still ongoing HIV epidemic.
  • Recovery Support Services for Opioid Use Disorder in Maryland: A Mixed Methods Study with a Two-Paper Dissertation

    Park, Eunsong; Unick, George Jay (2024)
    The alarming fatality rates associated with opioid use disorder (OUD) in the United States have triggered an increased level of public concern and awareness. Recognizing the urgency of addressing this crisis, adopting a fundamental proactive approach becomes imperative. Offering recovery support services (RSS) for individuals with OUD, in addition to treatment, emerges as a strategic pathway to guide society away from the opioid crisis. This two-paper dissertation is dedicated to comprehensively exploring RSS for individuals with OUD within Maryland. The first paper investigated the provision status of RSS across the local jurisdictions in Maryland. This investigation involved virtual interviews with key informants, examination of pertinent written documents, and online searches. While all jurisdictions had at least one service provider offering services for Mutual Support Groups, Care Coordination/Case Management, Medical Assistance Transportation, Harm Reduction, and Peer Support Services, considerable disparities in provision were observed among the twenty-four jurisdictions for the remaining RSS categories, RCC, WRC, Recovery Housing, Homeless Shelters, and Supported Employment Services. The second paper examined the associations between the provision of RSS, county-level covariates, and opioid overdose admission among jurisdictions in Maryland. In the second paper, the analysis incorporated the provision of RSS, the results from the first paper and secondary data including the Maryland State Emergency Department Database, Healthcare Cost and Utilization Project (2016-2020). Counties with more RSS were positively associated with opioid overdose admissions, compared to counties with fewer RSS. Drug overdose death rate, patient capacity rate, single-parent household rate, and non-Hispanic White rate were also positively associated with opioid overdose admissions. Notably, a significant reduction in opioid overdose admissions was observed in the year 2020 compared to the reference year, 2016.
  • Electromyographic activity and perceived exertion during the performance of a training protocol with internal focus direction in the bench press exercise

    Nascimento, P.H.F.; Lanza, Marcel B.; Andrade, A.G.P.; Caldeira, C.N.; Diniz, R.C.R.; Chagas, M.H.; Lima, F.V (2024-06-26)
  • Differences in Neuromechanical Factors Affecting Explosive Torque Production During Knee Extension: A Preliminary Comparative Study of Males and Females.

    Lanza, Marcel B.; Frakes, Nathan; Lateef, Shabnam; Baghi, Raziyeh; Rao, Sanjana; Zhang, Li-Qun; Gray, Vicki L. (2024-06-26)

View more