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The Effects Of Saha And Egcg On Metastatic Potential In Triple-Negative Breast Cancer Cells, Kayla Lewis Steed Jan 2019

The Effects Of Saha And Egcg On Metastatic Potential In Triple-Negative Breast Cancer Cells, Kayla Lewis Steed

All ETDs from UAB

About 1 in 8 women will be diagnosed with breast cancer at some time in their lives, and more than 40,000 women will die due to breast cancer this year. Women do not die from localized breast cancer cases but from metastatic, or Stage IV, breast cancer (MBC). Over 150,000 women are currently living with MBC, and treatments focus on length and quality of life considering there is no cure. Triple-negative breast cancers (TNBC) do not respond to targeted therapies as they are lacking estrogen receptor alpha (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). They …

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Bmp2-Derived Molecules For Increasing Osteoinductivity Of Bone Grafts To Enhance Bone Regeneration, Andrew Scott Curry Jan 2019

Bmp2-Derived Molecules For Increasing Osteoinductivity Of Bone Grafts To Enhance Bone Regeneration, Andrew Scott Curry

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The “gold standard” of bone grafting materials is autograft. Unfortunately, autogenous bone must first be harvested from the patient, leading to complications such as donor site morbidity. Because of this, many surgeons rely on non-autogenous bone grafting materials. While these grafts are more available than autogenous bone, they require extensive processing which significantly reduces their osteoinductivity. Therefore, there is substantial interest in finding ways to add osteoinductive molecules to these grafts. Previously, our lab has focused on utilizing molecules derived from bone morphogenetic protein 2 (BMP2) with an attached hydroxyapatite-binding domain (polyglutamate) to anchor them onto bone grafting materials. Previous …

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Racial And Gender Differences In The Relationship Between Adverse Childhood Experience And Chronic Health Conditions In Adulthood, Jalal Uddin Jan 2019

Racial And Gender Differences In The Relationship Between Adverse Childhood Experience And Chronic Health Conditions In Adulthood, Jalal Uddin

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A growing body of studies highlights that many adult diseases and health disparities in late-life are rooted in childhood adversities. However, there is little research that examines how social stratification processes structure the inequality in early-life stress exposure, and the effects of stress exposure on health outcomes may vary based on the intersections of social stratification categories. Drawing on an integrated framework of the life course stress process and intersectionality theory, this study examines the patterns in childhood adverse experiences (ACEs) by race/ethnicity and gender and how race/ethnicity, gender, and adult socioeconomic status (SES) combine to modify the effects of …

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Quantifications Of Theranostic Polymer-Based Particles For Image-Guided Drug Delivery, Sithira Ratnayaka Jan 2019

Quantifications Of Theranostic Polymer-Based Particles For Image-Guided Drug Delivery, Sithira Ratnayaka

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Modern medicine employs many drugs in its disease treatment methods. This is because they provide the best permanent solutions to complicated ailments. However the usefulness of these drugs is mitigated by several factors, namely that of specific release. Common drug delivery mechanisms lack the specificity needed to ensure that release is limited to the diseased area, which can lead to unnecessary side effects. By utilizing medical imaging, both drug delivery devices and physiology can be observed by physicians, which can greatly increase the specificity of drug delivery. Specifically, utilizing a very inert medical imaging modality, such as ultrasound, guarantees minimum …

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O-Glcnac Regulation Of Inhibitory Circuits, Kavitha Abiraman Jan 2019

O-Glcnac Regulation Of Inhibitory Circuits, Kavitha Abiraman

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Post translational modification of proteins plays a crucial role in regulating their function, and the role of one such modification, termed O-GlcNAcylation, is understudied. O-GlcNAcylation involves the dynamic cycle of adding and removing an O-linked N-acetylglucosamine (O-GlcNAc) by the enzymes O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), which are highly expressed in the hippocampus. Enzymes that catalyze O-GlcNAcylation are found at both presynaptic and postsynaptic sites, and O-GlcNAcylated proteins localize to synaptosomes. We have shown that acute and selective increase in O-GlcNAcylation of AMPAR GluA2 subunits underlies expression of a novel form of LTD at CA3-CA1 synapses (O-GlcNAc LTD), as well …

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Metal Complexation In Hydrogen-Bonded Microcapsules Of Poly(N-Vinylpyrrolidone) And Tannic Acid For Medical Imaging And Controlled Drug Delivery, Patrick Aaron Alford Jan 2019

Metal Complexation In Hydrogen-Bonded Microcapsules Of Poly(N-Vinylpyrrolidone) And Tannic Acid For Medical Imaging And Controlled Drug Delivery, Patrick Aaron Alford

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Even the most effective and widely used drugs in modern disease treatment can be compromised by low bioavailability and off-target damage which leads to detrimental side effects. Polymeric drug carriers have been developing in recent times with the aim of rendering the therapeutic cargo inert and protecting it from the body’s natural defense mechanisms until arrival at the target site, upon which a specific stimulus will cause the drug to release from the carrier locally. To this end, antioxidant capability in drug carriers can help mediate the cascade of reactive oxygen species that meet injected materials and, in doing so, …

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Mechanisms Of Acute Kidney Injury: The Role Of Ferritin Heavy Chain In Renal Heme-Unology, Laurence Marie Black Jan 2019

Mechanisms Of Acute Kidney Injury: The Role Of Ferritin Heavy Chain In Renal Heme-Unology, Laurence Marie Black

All ETDs from UAB

The kidneys are complex, multi-faceted organs that are responsible for regulatory processes, such as fluid homeostasis, hormone production, blood pressure regulation, and systemic toxin removal. Sudden disruption of these processes by acute kidney injury (AKI) causes rapid decline in renal function as well as significant morbidity and mortality. AKI is a significant clinical concern, affecting up to 13.3 million people globally each year and has the propensity to progress to chronic kidney disease (CKD), though the mechanism remains undefined. One reason for this is due to the lack of understanding of models used to study both AKI and CKD, hindering …

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An Ex Vivo Model Of Neuroendocrine Tumors: A Net Gain, Brendon R. Herring Jan 2019

An Ex Vivo Model Of Neuroendocrine Tumors: A Net Gain, Brendon R. Herring

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Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms that originate in a diverse array of anatomical locations and have widely variable clinical presentations and responses to treatment. Patient-derived xenografts and cell lines are valuable models of tumor biology and for testing personalized therapeutics on tumors prior to their administration to patients. However, as PDX models and cell lines for neuroendocrine tumors are lacking in both number and validity, we have developed a 3D flow perfusion polydimethylsiloxane (PDMS) bioreactor model for the purpose of culturing patient derived NETs. The goal of this thesis is to determine the ability to use …

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We Never Considered Teaching: A Critical Narrative Of African American Stem Majors’ Identity As Stem Educators, Paulette Georgina Evans Jan 2019

We Never Considered Teaching: A Critical Narrative Of African American Stem Majors’ Identity As Stem Educators, Paulette Georgina Evans

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The need to diversify and retain non-White STEM teachers in the educator workforce has brought to surface the need to more deeply understand why non-White educators choose teaching as a profession and, equally as important, why they choose to stay. Although there is literature documenting the shortages of African American teachers including how African Americans can be recruited and retained, there is a need to look more closely at how African American undergraduate STEM majors who are in innovative teacher preparation programs articulate their affinity to teaching. The following critical narrative study focuses on how pre-service non-White teachers, particularly African …

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St6gal-I Mediated Sialylation Promotes Pancreatic Ductal Adenocarcinoma Progression And Chemoresistance, Asmi Chakraborty Jan 2019

St6gal-I Mediated Sialylation Promotes Pancreatic Ductal Adenocarcinoma Progression And Chemoresistance, Asmi Chakraborty

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ST6Gal-I adds α2-6 sialic acids to select N-glycosylated cell surface receptors, thereby modulating receptor function and intracellular signaling. ST6Gal-I is upregulated in various carcinomas and confers cancer stem cell (CSC) properties evidenced by tumorspheroid growth, chemoresistance and tumor initiating potential. In pancreatic ductal adenocarcinoma (PDAC), ST6Gal-I conferred gemcitabine resistance by abrogating DNA damage and altering expression levels of gemcitabine metabolism genes. Further, ST6Gal-I promoted resistance to chronic gemcitabine treatment. Additionally, metastatic clones of a PDAC cell line had increased ST6Gal-I expression and ST6Gal-I knockdown enhanced gemcitabine sensitivity. To investigate the physiological consequences of ST6Gal-I in PDAC, murine models were used. …

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Modeling Resilience In Resetttled Syrian Refugees With Disabilities Living In The United States, Nicholas Ryan Sherwood Jan 2019

Modeling Resilience In Resetttled Syrian Refugees With Disabilities Living In The United States, Nicholas Ryan Sherwood

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Since 2011, the ongoing conflict in Syria displaces millions of individuals, many of whom have resettled across foreign borders. The US currently hosts 21,000 Syrian refugees, and of these, approximately 5,000 have at least one type of disability. This thesis asks of these individuals: given your experience as a person with a disability who has survived state-sanctioned violence and navigated forced migration, what have been your greatest sources of strength and resilience? Utilizing systems theory and a transdisciplinary approach, this thesis examines how three forms of identity promote community, interpersonal, and intrapersonal resilience within the target population.

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Transition Into Adulthood: Cannabis Use And Mental Health, Katie Mcintyre Jan 2019

Transition Into Adulthood: Cannabis Use And Mental Health, Katie Mcintyre

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The US is currently experiencing sweeping changes in the legal status of cannabis, the most common illicit drug used in America. Due to its classification as a Schedule I substance we know very little about how cannabis use impacts mental health since illicit drugs are not legally allowed to be researched in a laboratory setting. The current research on cannabis use (CU) and mental health (MH) is expansive and conflicting. One side of the debate suggests CU in adolescence has a direct effect on MH, the other side suggests CU could be an indirect coping mechanism of poor MH. One …

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Biopsychosocial Correlates Of Pain In Youth With Eosinophilic Esophagitis: A Comparison To Other Pediatric Patients, Mary Kenna Lynch Jan 2019

Biopsychosocial Correlates Of Pain In Youth With Eosinophilic Esophagitis: A Comparison To Other Pediatric Patients, Mary Kenna Lynch

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EoE is a chronic, clinico-pathological, esophageal disease with symptoms that include dysphagia, reflux, vomiting, feeding aversion, and epigastric pain. Diagnosis requires clinical symptom presentation and histologic findings of eosinophil-predominant inflammation of the esophagus. While the pediatric patient’s epigastric pain is predictive of their quality of life, little is known about their pain experience. Through two studies, the pain experience, sleep quality, and internalizing symptoms of youth with Eosinophilic Esophagitis (EoE) have been examined. Through individually evaluating each of these factors as well as testing their relations with each other, the model proposed by Lynch and colleagues (2015) to understand the …

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An Investigation Of Histocompatibility Testing And Mhc Class I In Xenotransplantation, Gregory Ryan Martens Jan 2019

An Investigation Of Histocompatibility Testing And Mhc Class I In Xenotransplantation, Gregory Ryan Martens

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In the United States, hundreds of thousands of patients suffer from end-stage organ failure or terminal diseases without the option of a life-saving transplant because of severe organ shortages. Xenotransplantation offers a possible solution by using genetically engineered pigs as organ donors. Application of pig-to-human organ transplantation has been limited by antibody-mediated rejection (AMR), but recent genetic engineering advances have eliminated pig glycan xenoantigens and dramatically reduced antibody binding. In human-to-human transplantation, allotransplantation, AMR is prevented by pretransplant screening donors and recipients. The major histocompatibility complex (MHC), class I and II, are primary targets for antibodies and may also bind …

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Appropriately Timed Epigenetic Manipulation With Histone Deacetylase Inhibitors As A Platform Approach To Tumor Immunotherapy, Tyler Mccaw Jan 2019

Appropriately Timed Epigenetic Manipulation With Histone Deacetylase Inhibitors As A Platform Approach To Tumor Immunotherapy, Tyler Mccaw

All ETDs from UAB

In contrast to chemotherapy and radiotherapy, immunotherapy is able to respond in proportion to tumor burden and continue to evolve in parallel with the tumor mass and metastatic sites. In this way, immune-based cancer therapies are a living drug and hold enormous potential. In this work, we enforce expression of MHCII on a murine breast cancer model to study how changes in tumor biology can drive improved T cell-mediated responses. We next use histone deacetylase inhibitors to manipulate the microenvironment through a more clinically relevant, therapeutic approach. Herein, improvements in tumor control were driven by CD8 T cells and IFNγ, …

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Occupational Therapy Students’ Perceptions Of Individuals With Mental Illness Before And After A Service-Learning Experience, Valley Mccurry Jan 2019

Occupational Therapy Students’ Perceptions Of Individuals With Mental Illness Before And After A Service-Learning Experience, Valley Mccurry

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Service-learning is a pedagogical approach that allows occupational therapy students to engage in experiential learning with individuals who have mental illness. Perceptions of individuals with mental illness are influenced by factors such as societal stigma. Stigma is present among allied health professionals and students, including occupational therapy students, which may influence provision of care. In order to assess occupational therapy students’ level of comfort with the mental health population, this study used a convergent mixed methods approach to evaluate how students’ personal beliefs and self-efficacy changed after a service-learning experience at a homeless shelter. The study explored occupational therapy students’ …

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Amyloid And White Mater Hyperintensity Burden In The Stroke Belt, Emily Carol Mckinley Jan 2019

Amyloid And White Mater Hyperintensity Burden In The Stroke Belt, Emily Carol Mckinley

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Several large cohort studies have found associations between residence in the Stroke Belt and cognitive impairment as well as dementia mortality; however, the rela-tionship between residence in the Stroke Belt and buildup of amyloid has not been estab-lished. The current project assessed the association between residence in the Stroke Belt and amyloid burden, amyloid accumulation, or white matter hyperintensities (WMH) in a large, national cohort of older US residents. The first study used linear regression models to examine the relationship between geographic residence and Centiloid values. Residence in the Stroke Belt at the time of baseline amyloid PET assessment was …

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Ribosomal Rna Synthesis Is Regulated By Pathways That Respond To Environmental And Stress Conditions, Saman Najmi Jan 2019

Ribosomal Rna Synthesis Is Regulated By Pathways That Respond To Environmental And Stress Conditions, Saman Najmi

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Ribosome biogenesis is one of the most central processes to cellular growth and metabolism. The synthesis of ribosomal RNA (rRNA) by RNA polymerase I (Pol I) is thought to be rate limiting for ribosome biogenesis, and is therefore subject to extensive regulation. The work presented in this dissertation characterizes two previously undiscovered pathways regulating rRNA synthesis. Due to the direct connection between ribosome biogenesis (and rRNA synthesis) and cellular proliferative potential, Pol I activity is upregulated in cancers. Cancer cells are hypersensitive to inhibition of Pol I, a quality that makes Pol I an attractive target for anticancer therapeutics. The …

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Genome Sequencing To Identify Novel Developmental Disorder Variation, Matthew Neu Jan 2019

Genome Sequencing To Identify Novel Developmental Disorder Variation, Matthew Neu

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The ability to quickly and accurately catalog an individual's genetic variation through genome sequencing has ignited a new era of diagnostic and therapeutic development for heritable disease. Although genome sequencing can provide a molecular diagnosis in a significant number of patients with suspected genetic disease, there remain a number of unsolved cases for which no pathogenic cause can be determined. This uncertainty can create a "diagnostic odyssey" in which sequential tests fail to provide a diagnostic resolution and can often delay beneficial treatment, impact family planning, and be emotionally challenging for patients and their families. Clearly, there is an unmet …

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Dna Template Sequence Effects On Rna Polymerase I Transcription Elongation, Andrew Martin Clarke Jan 2019

Dna Template Sequence Effects On Rna Polymerase I Transcription Elongation, Andrew Martin Clarke

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The production of ribosomes represents the major synthetic effort of a rapidly dividing cell, and is intimately linked to the regulation of cell growth and proliferation. Developing a greater understanding of the mechanisms that regulate ribosome biogenesis is therefore crucial to understanding cellular control of the growth cycle. Ribosome biogenesis begins with the synthesis of the 35S ribosomal RNA (rRNA) by RNA polymerase I (Pol I). This RNA is co- and post-transcriptionally processed to produce the 18S, 5.8S, and 25S rRNAs. These RNAs are critical components of ribosomes, and Pol I has been demonstrated to be a key regulation target …

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Examining The Role Of The Unfolded Protein Response In Depression, Matthew Timberlake Jan 2019

Examining The Role Of The Unfolded Protein Response In Depression, Matthew Timberlake

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Depression is the leading cause of disability worldwide and impacts nearly 350 million people with a disproportionate representation in women with a 1:1.7 ratio of occurrence compared to men. This disorder is characterized by shifts in mood to include feelings of hopelessness, sadness, and lethargy as well as changes in diet, motivation, and sleep patterns. Further, over 50% of patients who struggle with depression also have suicidal ideation and as many as 10% of those commit suicide. At present, treatment plans include behavioral therapy (often) in conjunction with antidepressant medications which act on monoamines and their circuits in the central …

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Influencing The Positive Mental Health Of Non-Kinship Foster Children: The Lived Experiences Of Foster Parents In Alabama, Sarah Catherine Tucker Jan 2019

Influencing The Positive Mental Health Of Non-Kinship Foster Children: The Lived Experiences Of Foster Parents In Alabama, Sarah Catherine Tucker

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This Interpretive Phenomenological Analysis (IPA) qualitative study interviewed fifteen non-kinship foster parents in Alabama to explore their lived experiences of influencing the positive mental health of their foster children. This phenomenological approach allowed for a deeper understanding of the challenges foster caregivers face when facilitating improved psychological and social well-being of their foster children. In 2015, there were 427,910 children in foster care, with 45% of these children residing in a non-kinship foster home (Adoption and Foster Care Analysis and Reporting System [AFCARS], 2016). Children in foster care, especially children in non-kinship care arrangements, often have significant and complex mental …

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Effect Of Antidepressants On Cytokines Profiles Seen In Inflamed Tissue And Serum Samples In Patients With Moderate Chronic Periodontitis, Silvia M. Villalobos Jan 2019

Effect Of Antidepressants On Cytokines Profiles Seen In Inflamed Tissue And Serum Samples In Patients With Moderate Chronic Periodontitis, Silvia M. Villalobos

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This study evaluated whether depression with or without the use of antidepressant was associated with changes in inflammatory markers, intraorally and systemically, GCF volume, serum biomarker levels. Cross-sectional data were collected from individuals with moderate periodontitis who were assigned to one of three groups based upon their medical history, medication usage, and answers to a validated survey instrument that assessed their level of clinical depression. Three groups of patients were compared: 1) patients with clinically diagnosed depression taking antidepressant medications [selective serotonin reuptake inhibitors (SSRIs), norepinephrine-dopamine reuptake inhibitor (NDRIs), or serotonin and norepinephrine reuptake inhibitors (SNRIs)]. 2) patients with clinically …

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Novel Biomarkers For Parkinson Disease, Shijie Wang Jan 2019

Novel Biomarkers For Parkinson Disease, Shijie Wang

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Parkinson disease (PD) is the second most common neurodegenerative disorder with no reliable biochemical biomarkers for disease prediction or progression, nor disease-modifying treatments to slow the relentless progression. Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are known to increase LRRK2 kinase activity and increase the risk for late-onset PD. In this thesis, I discovered that LRRK2 is secreted into exosomes in urine and CSF, where LRRK2 kinase activity, reflected by autophosphorylation at pS1292 site, is preserved and reflective of cytosolic LRRK2 levels. In a cohort of biosamples from LRRK2 mutation carriers and matched controls, with and without PD, …

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Discovering The Genetic Architecture Underlying Exercise Response Using Drosophila Melanogaster, Louis P. Watanabe Jan 2019

Discovering The Genetic Architecture Underlying Exercise Response Using Drosophila Melanogaster, Louis P. Watanabe

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The growth of modern jobs, technology, and transportation has coincided with increased sedentary behavior in many developed nations. In the United States, this increase has contributed partially to rising rates of obesity, leading to more than 78 million obese individuals. The annual medical costs associated with obesity are thought to range from 147 to 210 billion dollars. The initial treatment recommendations for individuals with obesity are increased exercise and changes in diet. Despite the strong narrative pushing exercise as a health benefit, individual responses can vary widely, and little is known regarding the genetic networks modulating exercise response. In order …

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Using Peptide Mimetics To Probe Protein-Protein Interactions Significant In Cancers, Robert H. Whitaker Jan 2019

Using Peptide Mimetics To Probe Protein-Protein Interactions Significant In Cancers, Robert H. Whitaker

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Protein-protein interactions are critical for cell life. One aspect of cellular regulation where such protein-protein interactions occur is in the highly regulated process of programmed cell death (or apoptosis). Apoptosis is critical for normal tissue homeostasis, differentiation, and if dysregulated is a driver of disease including cancers. At the center of apoptotic regulation is the BCL2 protein family whose intra-familial protein-protein interactions balance cell stress signaling either allowing the cell to survive or inducing mitochondrial cell death. These BCL2 protein interactions are accomplished through the BH3 motif. While unique to the BCL2 family, a similar motif, the reverse BH3, has …

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Perceptions Of The Police By Queer Women, Marshall Lorraine White Jan 2019

Perceptions Of The Police By Queer Women, Marshall Lorraine White

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Queer communities have historically had a strained relationship with the police. In recent years, scholars have begun to examine perceptions of the police by these communities in an attempt to fill an important gap in the literature. The current study examines perceptions of the police by queer women in Birmingham, AL. The focus on queer women is attributed to recent findings that queer women (lesbian, bisexual, transgender, etc.) report more negative perceptions of the police than others in queer communities. Semi-structured interviews were conducted with 17 self-identified White, queer women about their experiences growing up, broad views about the police, …

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Examining Web-Based Lifestyle Interventions For Cancer Survivors, Victoria Williams Jan 2019

Examining Web-Based Lifestyle Interventions For Cancer Survivors, Victoria Williams

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Diet, physical activity, and body weight status are important modifiable risk factors for many health outcomes among cancer survivors, including cancer recurrence. Face-to-face, print, and mailed lifestyle interventions have been used to promote behavior change in cancer survivors successfully. However, such approaches are costly and have limited reach. Web-based lifestyle interventions represent a promising solution to this public health concern. Therefore, this project involved first reviewing and identifying gaps in the existing literature in this area and then developing and pilot testing a web-based lifestyle intervention for cancer survivors. For this three-part dissertation, study 1 was a narrative review of …

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Genetic And Epigenetic Underpinnings Of End-Stage Human Heart Failure, Mark Emile Pepin Jan 2019

Genetic And Epigenetic Underpinnings Of End-Stage Human Heart Failure, Mark Emile Pepin

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Heart failure (HF) is the clinical endpoint of numerous diseases that negatively impact the heart’s capacity to pump and/or fill with blood. A variety of genetic and environmental factors have been identified as critical determinants of HF susceptibility; however, these factors cannot independently explain the phenotypic diversity of human HF. Instead, a complex interplay has been theorized to exist between genetics and the environment, although the molecular underpinnings of this synergy remain poorly understood. Of the possible mechanisms, epigenetic influences are uniquely capable of explaining how acute stressors of the cardiac microenvironment trigger the stable – yet reversible – reprogramming …

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The Closed Eye As A Model For Dry Eye Disease, Cameron Kenneth Postnikoff Jan 2019

The Closed Eye As A Model For Dry Eye Disease, Cameron Kenneth Postnikoff

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Every night, during sleep, the tears of the closed eye become significantly more inflammatory, with a notable influx of neutrophils. Preliminary studies suggested that these neutrophils were significantly different than blood-isolated neutrophils, with an increased concentration, upregulated surface expression of inflammatory membrane receptors, but inability to respond to inflammatory stimuli. The purpose of this dissertation was to better understand the contribution of this neutrophil population to ocular surface homeostasis and dry eye disease. Chapter One presents an introduction to the tear film and ocular surface, along with an introduction to dry eye disease and neutrophil biology. Chapter One also discusses …

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