Life Sciences Commons^™

Exploring Factors That Contribute To Poverty Among Singleparent Households Headed By Latinas: A Qualitative Study, Jeffrey M. Balencia

Electronic Theses, Projects, and Dissertations

Background: Despite the new strategies and programs being developed and implemented, poverty still finds itself at a continuous increase yearly (Banovcinova et al., 2014). Families have been found to be the most susceptible group compared to everyone else due to the many factors they face that can affect them. By using the information provided by other articles, gaps identified is there are lack of studies on the factors that contribute to poverty among singleparent households headed by Latinas. Objective: This exploratory study aims to identify contributing factors to poverty among single-parent households headed by Latinas. Method: Qualitative data will be …

Therapeutic Vulnerabilities Of Venetoclax Resistant Chronic Lymphocytic Leukemia And Novel Treatment Strategies Targeting Bcl2/Bcl-Xl, Daisy Y. Diaz-Rohena

Dissertations and Theses (Open Access)

Despite major advancements in the management of chronic lymphocytic leukemia (CLL), drug resistance remains a major challenge. CLL resistant to venetoclax (VEN) have limited available therapeutic options, especially when the leukemic cells have dysfunctional p53 and have relapsed on Bruton’s tyrosine kinase inhibitors (BTKi). The broad hypothesis of this thesis is that VEN-relapsed CLL exhibits altered dependence on BCL2 family members, which can be exploited for therapeutic benefit. I profiled 28 CLL samples collected from 15 patients either at baseline or at relapse following VEN treatment, which was administered in combination with a BTKi or sequentially as monotherapy after a …

Ascl2 Positive Tumor Cells Modulate The Response Of Metastatic Colorectal Cancer To Mapk-Targeting Therapy, Oscar Eduardo Villarreal

Dissertations and Theses (Open Access)

Colorectal cancer (CRC) is the second leading cause of cancer related deaths with nearly a quarter of patients presenting with metastatic disease at the time of their diagnosis. Therapeutic management of metastatic CRC continues to be a major challenge due to therapy resistance and disease heterogeneity. Due to its central role in tumorigenesis, CRC is commonly treated with MAPK pathway inhibitors (MAPKi). However, clinical trials repeatedly demonstrates that durability of benefit is short-lived in many patients. While genomic mechanisms of acquired resistance have been described, they explain a minority of patients, and further research is needed to determine the underlying …

Microplastics In Coastal And Marine Environments: A Critical Issue Of Plastic Pollution On Marine Organisms, Seafood Contaminations, And Human Health Implications, Rebecca Muñiz, Md. Saydur Rahman

School of Earth, Environmental, & Marine Sciences Faculty Publications

Plastic has quickly become one of the world's most prevalent environmental pollutants. Population growth has only amplified the demand, resulting in 430 million tons of plastic produced annually, with 11 million tons ending up in our oceans. Without intentional intervention, plastic waste in the oceans is expected to triple, posing severe risks for the aquatic ecosystems, animals, and humans dependent on these waters. As plastic accumulates in oceans and other water environments, the non-biodegradable particles break down into micro- and nano-plastics, invading coastal and marine organisms and causing considerable physiological and morphological damage. This is especially concerning for the millions …

The Roles Of Rnt1 And Putative Endoribonucleases In Eukaryotic Mrna Degradation, Lee-Ann Notice-Sarpaning

Dissertations and Theses (Open Access)

Endoribonucleases initiate degradation by cleaving RNAs internally. Mutations in these enzymes have been shown to cause diseases such as cancer, developmental disorders, and neurodegenerative diseases. Yet, eukaryotic endoribonucleases have not been well studied, especially with regard to their role in nuclear mRNA degradation. Rnt1 is a Saccharomyces cerevisiae (budding yeast) nuclear endoribonuclease and homolog of human Drosha with well-characterized roles in the processing of ncRNAs. The enzyme recognizes and cleaves double-stranded RNA stems containing a terminal tetraloop with an AGNN consensus sequence. However, the scope and consequence of its function in mRNA degradation has heretofore been unclear. Previous studies have …

Leveraging Innate Immune Sensors To Generate Durable Anti-Glioma Adaptive Immune Responses, Spencer Lea

Dissertations and Theses (Open Access)

Glioblastoma is an aggressive primary brain malignancy harboring a tumor microenvironment that is mostly devoid of T cell effector infiltration but is dominated by immune suppressive microglia, macrophages, and myeloid-derived suppresser cells. These innate immune cells display impaired phagocytosis and antigen presentation and are inadequate for triggering the subsequent immune activating signals needed for anti-tumor adaptive effector responses. Glioblastoma tumors can further restrict phagocytosis and subsequent tumor antigen presentation by the upregulation of the antiphagocytic “don’t eat me” ligand CD47. Here we tested whether activation of multiple conserved innate immune pathways could initiate proinflammatory conversion of suppressive myeloid populations, activation …

Identification Of Mitochondrial Defects And Metabolic Consequences In Lynch Syndrome-Related Endometrial Cancer, Mikayla Bowen

Dissertations and Theses (Open Access)

Lynch syndrome (LS), defined by mutations in DNA mismatch repair genes including MSH2, carries a 60% lifetime risk of developing endometrial cancer (EC). Mismatch repair deficiency (MMRd) causes hypermutability, which is assumed to be the main driver of LS-related EC development. However, incomplete penetrance of EC development in women with LS suggests that other modulators are at play. The broad hypothesis of this dissertation is that MMRd causes consequences beyond hypermutability to impact LS-related EC development. Recent studies utilizing our lab’s Msh2-deficient mouse model for LS-EC revealed mitochondrial dysfunction in EC pathogenesis. This new insight led to the …

Unraveling Epigenetic Mechanisms That Regulate Breast Cancer Lung Metastatic Relapse By Rewiring The Immune Microenvironment, Jayanta Mondal

Dissertations and Theses (Open Access)

Metastasis accounts for >90% of cancer-related deaths and thwarting metastasis is widely considered to be the “Holy Grail” of cancer treatment. Breast cancer is the most common cause of cancer-related death among women and is characterized by its proclivity to spread to distant secondary organs like the lungs, and the brain. These disseminated tumor cells lie dormant at the secondary site and can undergo metastatic relapse. Epigenetic alterations are a predominant hallmark of cancer, however, its role in facilitating reawakening of dormant cancer cells and the subsequent metastatic relapse remains to be elucidated. To address this gap of knowledge, we …

Developing Novel Therapies Targeting The Tumor Microenvironment Of Aggressive Breast Cancer, Lan T H Phi

Dissertations and Theses (Open Access)

Triple-negative breast cancer (TNBC) and inflammatory breast cancer (IBC) are the most aggressive breast cancer subtypes. The tumor microenvironment (TME) is critical in driving these aggressive breast cancers' clinical phenotype and aggressiveness. Therefore, we explored novel actionable targets and complementary therapies targeting the TME to improve the outcomes of patients with these cancers.

In this thesis, we identified AXL as a potential therapeutic target in IBC due to its role in generating an immunosuppressive TME. Indeed, inhibiting the AXL pathway suppresses IBC tumor growth and reduces M2 macrophage populations in various mouse models. Mechanistically, AXL facilitates the polarization of M2 …

Impact Of Tumor Cell Expressed Cd38 On Metastasis And Immune Evasion In Breast Cancer, Tanvi Visal

Dissertations and Theses (Open Access)

Triple-negative breast cancer (TNBC) is a highly metastatic breast cancer subtype. The epithelial-to-mesenchymal transition (EMT) of cancer cells is a key feature of the metastatic cascade and is not a binary process but often generates malignant cells with both epithelial (E) and mesenchymal (M) traits known as hybrid EM cells. Recent studies highlight the enhanced metastatic potential of the hybrid EM cells. However, molecular insights and targetable vulnerabilities within hybrid EM remain elusive. We discovered that hybrid EM murine tumors are enriched in CD38, an immunesuppressive molecule associated with worse clinical outcomes in liquid malignancies but relatively understudied in solid …

The Extracellular Domains Of The Ampa, Kainate, And Orphan Delta Receptor Regulate Channel Gating In Distinct Ways, Cuauhtemoc Ulises Gonzalez

Dissertations and Theses (Open Access)

The ionotropic glutamate receptors are ligand-gated cationic channels essential for neuroplasticity and neurological functions such as learning, memory, behavior, cognition, and motor coordination. Mutations in these channels are linked to various disorders including autism, ataxia, and epilepsy, making them compelling pharmacological targets. Within this family, the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and kainate receptor mediate their function through fast glutamate-gated ionotropic activity, which needs precise structural changes to perform properly. While Cryo-EM structures have provided snap shots of these proteins, questions remain regarding the dynamics across conformations and individual roles of the extracellular amino-terminal and agonist binding domain in dictating function. …

Evaluating Cancer Rates, Cancer Types, And Variant Hotspots Between Different Races And Ethnicities In Individuals With Li-Fraumeni Syndrome, Hillary Esplen

Dissertations and Theses (Open Access)

Li Fraumeni Syndrome (LFS) is a cancer predisposition syndrome that increases the risk for numerous cancer types in both children and adults. In the general population, incidence rates for various cancer types differ among races and ethnicities. Although a few germline TP53 pathogenic/likely pathogenic (P/LP) variants in those with LFS have been studied and associated with specific populations, such as the South and Southeast Brazil founder variant, p.Arg337His, there still lacks research on the variable expressivity of cancers within the LFS population based on specific variant, race and/or ethnicity. This study aims to describe the specific TP53 germline variants, the …

Relationship Between Processing Body Formation, Epithelial-To-Mesenchymal Transition, And Invasion In Lung Adenocarcinoma, Amanda Warner

Dissertations and Theses (Open Access)

Lung cancer is the leading cause of cancer-related deaths in the United States, largely due to its ability to metastasize. Epithelial-to-mesenchymal transition (EMT) is a process that enhances the ability of cells to lose their cell-cell contacts, invade, and enter the blood stream which are essential during metastasis. Many transcriptional gene programs are altered during EMT such as activation of mesenchymal transcription factors, like ZEB1, and enhanced response to the TGFβ1 cytokine. In oncogenic contexts, TGFβ1 enhances the formation of processing-bodies (P-bodies) where P-body proteins are required for invasion in multiple cancerous cell lines. P-bodies are a type of ribonucleoprotein …

Rod Photoreceptor Regeneration In A Zebrafish Model With Retinitis Pigmentosa, Eyad Shihabeddin

Dissertations and Theses (Open Access)

A cellular hallmark of inherited retinal degenerative diseases is progressive loss of photoreceptors until one is completely blind. Unlike mammalian models, Zebrafish have the ability to naturally regenerate their neurons after injury or disease is detected. We have generated a zebrafish model with the most common autosomal dominant form of the inherited retinal degenerative disease known as Retinitis Pigmentosa. We utilize immunohistochemistry, single-cell RNA sequencing, several analysis tools, behavioral assays and oligonucleotides to characterize our zebrafish model and identify the transcription factors necessary for rod photoreceptor regeneration. We show that our zebrafish model has continuous degeneration and regeneration of rod …

Exploring Veto Activity: Dnam-1-Cd155 Axis In Overcoming Nk Cell-Mediated Allo-Rejection And Applications For Car-T Cell Therapy, Wei-Hsin Liu

Dissertations and Theses (Open Access)

As Miller et al. defined veto activity, it enables cells to target host cytotoxic T lymphocyte (CTL) precursors specific to veto cells' antigens, selectively eliminating anti- donor T cell clones without inducing rejection. By leveraging this unique immune property, two key research aims were proposed: “Exploration of the Impact of Veto Activity on Natural Killer (NK) Cell-Mediated Allo-rejection” and “Development of Off-the- shelf Chimeric Antigen Receptor (CAR)-T Therapy: Engineering Anti-Viral Veto CD8+ T Cells”. As demonstrated in our previous research, in a murine model with mild conditioning, anti-third-party central memory CD8+ veto T cells (veto Tcm) can prevent T cell- …

The Gut Microbiome As A Novel Approach For Reversing Long-Term Inflammation And Accelerated Aging Across The Lifespan, Janelle M. Korf

Dissertations and Theses (Open Access)

Introduction: Neonatal hypoxic-ischemic encephalopathy (HIE) arises from disrupted perinatal cerebral oxygenation and perfusion. It is a leading global cause of infant death and disability which disproportionally affects males. Like adult stroke, HIE initiates a rapid influx of inflammatory cells across the blood brain barrier and a loss of microglial homeostasis. Persistent peripheral inflammation in children with a history of HIE is recognized but its ramifications, including accelerated aging, are poorly understood. As this coincides with critical stages of brain development, interventions started months or years post-injury may still improve survivors’ quality of life. One promising intervention is to manipulate the …

Overcoming Resistance To Cdk4/6-Targeted Therapy Using Jak2/Stat3 Inhibitor In Triple-Negative Breast Cancer, Chuling Zhuang

Dissertations and Theses (Open Access)

Breast cancer is the most common type of cancer diagnosed in women, with nearly 30% of cases becoming metastatic accounting for over 90% of breast cancer-related deaths. Among different breast cancer subtypes, triple-negative breast cancer (TNBC) has the worst prognosis and the highest propensity to metastasize. However, TNBC patients have limited treatment options due to their lack of actionable drug targets while therapeutic resistances result in high rates of recurrence and metastasis. Cyclin-dependent kinase 4 and 6 (CDK4/6) are major cell cycle regulators that control G1 to S phase transition and aberrant hyperactivation of the CDK4/6 pathway results in uncontrolled …

Elucidating The Multi-Omics Of Early-Onset Colorectal Cancer, Jumanah Alshenaifi

Dissertations and Theses (Open Access)

The incidence and mortality rates of sporadic early-onset colorectal cancer have increased in recent decades, but there is no clear etiological basis for this trend. EOCRC is commonly defined as colon and rectal cancers diagnosed before the age of 50 years. The rising incidence of EOCRC has made it the second most common cancer and the third leading cause of cancer death in this age group. The rising incidence of EOCRC is also documented internationally in more than 20 countries across different continents. Clinically, EOCRC has a distinct, more aggressive clinical profile than LOCRC. While approximately 15% of EOCRC cases …

Impact Of Personal And Family History Of Huntington's Disease On The Decision And Ability To Obtain Life, Long-Term Care, And Disability Insurance, Karli Livingston

Dissertations and Theses (Open Access)

Huntington’s disease (HD) is an inherited, neurodegenerative condition characterized by a clinical triad of motor, cognitive, and psychiatric symptoms. Individuals diagnosed with HD manifest characteristic symptoms of the disease including motor and cognitive changes, and they may or may not have undergone genetic testing to confirm the diagnosis. Individuals at-risk for HD are those who have not yet undergone genetic testing for HD, but have a first- or second- degree relative diagnosed with the disease. Genetic testing for HD is categorized into two forms: predictive and confirmatory. However, many individuals choose not to pursue testing due to a fear of …

The Influence Of Scientific, Genetic, And Health Literacy On Carrier Screening Decision-Making, Brenna D. Albracht

Dissertations and Theses (Open Access)

For those wishing to assess their reproductive risks and make informed decisions in their reproductive planning, carrier screening for autosomal recessive and X-linked conditions, as well as cell-free DNA (cfDNA) screening for aneuploidy, are recommended during pregnancy. Despite similarities in purpose, sample requirements, insurance coverage, and safety, a lower percentage of individuals elect carrier screening than cfDNA screening, suggesting there may be a disconnect in what patients perceive as valuable information for their pregnancy. Previous studies have attempted to explain the factors associated with carrier screening uptake or decline; however, no models have yet accounted for a patient’s literacy level …

Identifying And Characterizing Transition Cells In Developmental Processes From Scrna-Seq Data, Yuanxin Wang

Dissertations and Theses (Open Access)

During the development of multicellular organisms, individual cells make distinct decisions about their cell types and states. Understanding the molecular mechanisms underlying cellular state transitions at different developmental stages provides deep insights into physiology, morphology and the etiology of diseases. Single-cell RNA-sequencing (scRNA-seq), which is widely used to study complex cell states and dynamic gene expression patterns, enables us to investigate molecular mechanisms of cellular state transitions. Currently, however, computational tools available for identifying cellular states and state transitions remain limited.

Although trajectory-based methods such as Monocle and Slingshot assume that state transitions generate continuous expression profiles, they cannot distinguish …

Harnessing The Immunomodulatory Potential Of Radiofrequency Ablation To Improve Therapeutic Outcomes In Pancreatic Ductal Adenocarcinoma, Bhumi Maniyar

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) continues to rank among the most lethal cancers with poor prognosis. PDAC is characterized by a thick desmoplastic stroma, severe immunological suppression, and resistance tostandard treatments. The need for innovative therapeutic approaches is highlighted by the tumor microenvironment's (TME) critical role in promoting disease development and reducing the effectiveness oftreatment. A promising locoregional treatment that can induce tumor necrosis and modify the TME is endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA). However, there is still minimal understanding around its wider impact on stromal remodeling and immunological activation. This study investigates the immunomodulatory effects of RFA combined with neoadjuvant …

Role Of Mir-4732-3p In Breast Cancer Brain Metastasis And Brain Metastatic Tumor Microenvironment, Munazza Samar Khan

Dissertations and Theses (Open Access)

In this study, we aimed to identify microRNAs (miRNAs) that may play important roles in breast cancer brain metastasis (BCBM). To this end, we conducted miRNA-sequencing of extracellular vesicles isolated from the serum samples of 6 BCBM patients and 8 Stage I/II/III breast cancer patients, and identified 49 circulating miRNAs that were upregulated in BCBM patients compared to Stage I/II/III breast cancer. Upon further analysis, we identified miR-4732-3p to be upregulated in brain-tropic triple-negative breast cancer (TNBC) cell lines, compared to parental lines. MiR-4732-3p overexpression increased metastatic properties of TNBC cells, including proliferation, migration, invasion, and maintenance of a mesenchymal …

Uncovering A Fundamental Mechanism Underlying Female Oocyte Quality And Rasopathies Using C. Elegans As A Model System, Han Bit Baek

Dissertations and Theses (Open Access)

Signaling pathways are molecular networks that allow cells to communicate between and within themselves. They are crucial for the coordination of diverse cellular processes and are the molecular mechanism in which cells sense and respond to their environment. RAS (Rat Sarcoma) is a small GTPase that transmits extracellular growth factor signals through a downstream kinase cascade and ERK (Extracellular-signal regulated kinase) is the terminal kinase, and it controls cellular processes such as proliferation, differentiation, and survival by phosphorylating its downstream effectors. This post translational modification regulates the effector by modulating its activity, levels, and/or interaction with other molecules. Given the …

"Magic Computer In The Sky" - Participant Perspectives On Control And The Genetic Counseling Admissions Match, Jessica Clark

Dissertations and Theses (Open Access)

Since the 2018 admissions cycle, genetic counseling graduate programs in North America have utilized the Genetic Counseling Admissions Match (GCAM), a Match algorithm to place applicants. While a study prior to implementation found that most students were uninterested in a Match due to concerns of control, there has been no investigation into matched applicants’ experiences since its inception. A mixed-methods study explored the experiences and perceptions of control of genetic counselors and genetic counseling (GC) students who entered a program following the GCAM. An anonymous survey documenting GCAM experience and a validated measure for locus of control (LOC) was disseminated …

Exploring The Immunologic Consequences Of Atrx Deficiency In Glioma, Benjamin Whitfield

Dissertations and Theses (Open Access)

ATRX is a key chromatin regulator that is frequently mutated across multiple cancer types. One of the most common ATRX-mutated tumor types is the adult-type glioma, IDH-mutant, Astrocytoma. It is known that ATRX mutation leads to increases in DNA damage, replication stress, and global epigenetic regulation at a cell level; however, less is known about the impact of ATRX mutation on immune signaling. Furthermore, little is known about the interaction of ATRX loss with gain-of-function mutations in IDH. In this paper we set out to explore the impact of ATRX loss on immune signaling in gliomas, both in the context …

Investigating Prefrontal Cortex Neuronal Signatures Of Opioid-Induced Risk-Taking Behavior, Cana Quave

Dissertations and Theses (Open Access)

Opioid use disorder occurs alongside impaired risk-related decision-making, but the underlying neural correlates are unclear. We developed an approach-avoidance conflict task using a modified conditioned place preference procedure to study neural signals of risky opioid seeking in the prefrontal cortex, a region implicated in executive decision-making. Following morphine conditioned place preference, rats underwent a conflict test in which fear-inducing cat odor was introduced in the previously drug-paired side of the apparatus. While the saline-exposed control group avoided cat odor, the morphine group included two subsets of rats that either maintained a preference for the paired side despite the presence of …

Stat3, Nf-Κb, And Estrogen Receptor Beta: The Balance Of Inflammation In K-Ras Mutant Lung Adenocarcinoma, Michael J. Clowers

Dissertations and Theses (Open Access)

K-ras mutant lung adenocarcinoma (KM-LUAD) is a difficult-to-treat cancer subtype in which chronic inflammation pervades the tumor immune microenvironment (TIME). Pro-inflammatory pathways dampen the response to treatments, including immune checkpoint inhibitors, necessitating therapies that target this inflammatory signaling network in the TIME. This network is underpinned by interaction and coordination of two inflammatory pathways: signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa B (NF-κB). The balance of these transcription factors determines the degree of anti- vs. pro-tumor immunity, and a skewing towards STAT3 is known to promote tumor development and a pro-tumor TIME. It is also …

Mhc Class I Tyrosine Phosphorylation Site Y320 Augments Cd8+ T Cell Priming, Effector Function, And Memory Response, Yimo Sun, Gregory A Lizee, Yitao Tang, Priscilla Ortiz, R Eric Davis

Dissertations and Theses (Open Access)

The cytoplasmic domain of MHC class I (MHC-I) molecules contains a single, highly conserved tyrosine residue (Y320). In previous work, we found that mice expressing a Y320F-mutated form of H-2K^b had reduced capacity to generate K^b-restricted cytotoxic T lymphocyte (CTL) responses following viral infection, due (at least in part) to defects in endolysosomal trafficking of H-2K^b and antigen cross-presentation by dendritic cells (DCs). In this study, we investigated whether there are additional, post-presentation dependencies on Y320 for T-cell priming. We engineered both human- and mouse-derived antigen-presenting cells (APCs) to express either wild-type MHC-I or variants of …

Evaluating Triage To Genetic Counseling Using An Online Reproductive Genetics Module, Grace Ra

Dissertations and Theses (Open Access)

The American College of Obstetricians and Gynecologists recommends genetic screening for all pregnant women. As clinical recommendations broaden and demand for prenatal screening increases, obstetric practitioners report time constraints and lack of genetics knowledge as challenges to providing sufficient pretest education. These challenges in offering routine screening are further compounded by the inequities in access to genetic counseling and testing. Thus, alternative education and service delivery models have emerged to meet the demands for prenatal genetics education and help mitigate challenges surrounding access. At UTHealth Houston, an online triage and education module, the Prenatal Genetics Education Program (PGEP), was created …