Antigen Discovery In Multiple Myeloma Using Integrated Long-Read Transcriptomics And Immunopeptidomics, Aya Albittar

Dissertations and Theses (Open Access)

Multiple myeloma (MM) remains an incurable plasma cell malignancy, with relapse driven by persistent chemotherapy-resistant cells and residual disease following treatment. Although immunotherapies have transformed MM care, their success depends on identifying tumor-specific antigens that can be safely targeted. While aberrant genomic structural variation and transcriptional dysregulation are increasingly recognized as sources of novel antigens in MM, the HLA-presented antigenic landscape of MM remains incompletely characterized, particularly for non-canonical, structurally-derived peptides, and long-read transcriptome-informed immunopeptidomic data specific to MM remain scarce.

We established an integrated antigen discovery platform combining long-read RNA sequencing (Iso-Seq) with mass spectrometry-based HLA immunoprecipitation and immunopeptidomics …

Agent-Based Modeling Of Cellular Dynamics In Adoptive Cell Therapies, Yujia Wang

Dissertations and Theses (Open Access)

Adoptive cell therapies (ACT) have shown promising progress in combating cancer, but clinical responses remain heterogeneous. Key determinants, including the functional states of infused cells, tumor–immune interactions, and dosing strategies, are difficult to resolve experimentally in the dynamic and heterogeneous tumor microenvironment, limiting optimization of ACT products and treatment regimens. To address the gap, we developed ABMACT (Agent-Based Model for Adoptive Cell Therapies), a computational framework that reconstruct key cellular functions, interactions, and molecular signatures to recapitulate cell population dynamics associated with differential treatment responses. ABMACT encodes autonomous “virtual cells” using literature-informed rules calibrated with experimental data, enabling simulation of …

Ai-Driven Segmentation And Volumetric Response Modeling Of Liver Regions To Radiotherapy, Aashish Chandra Gupta

Dissertations and Theses (Open Access)

In liver-directed radiotherapy (RT), liver regions receiving higher doses typically undergo atrophy while contralateral/adjacent lower-dose regions may exhibit compensatory hypertrophy through regeneration of healthy tissue. Optimizing the RT plan to promote regional hypertrophy while minimizing the risk of developing atrophy has the potential to enhance post-RT liver function and long-term survivorship. However, current clinical practice largely relies on global liver dose-volume metrics during RT-planning, which may obscure favorable dose-response correlation and limit actionable guidance for clinicians. Therefore, we hypothesized that post-RT regional liver response is governed by a combination of region-specific dose-volume and patient clinical features, and that these responses …

Regulation Of Müllerian Duct Mesenchyme Transcription During Mammalian Sex Differentiation, Haowen Li, Richard R Behringer, Rachel D Mullen

Dissertations and Theses (Open Access)

Sp7/Osterix (Osx) encodes a zinc-finger transcription factor of the Specificity-protein family discovered by Nakashima et al. at the MD Anderson Cancer Center. While primarily recognized for its role in osteogenesis, Osx has also been implicated in mammalian reproductive development, particularly in male sex differentiation, where Müllerian Duct (MD) regression occurs, mediated by anti-Müllerian hormone (AMH) signaling. AMH-induced regression signals are transduced by the mesenchymal tissue surrounding the ductal structure, known as the Müllerian Duct mesenchyme (MDM). It was discovered that AMH signaling is necessary and sufficient for driving Osx expression in MDM. A previous transgenic mouse reporter …

Newly Registered Nurses With Neurodiversities: A Qualitative Study Of Their Experiences During Transition To Professional Practice, Heather Wallace

Dissertations and Theses (Open Access)

Abstract Introduction: Transition-to-practice (TTP) programs play a crucial role in bridging the academic-to-practice gap for newly licensed Registered Nurses (NLRNs) and improving first-year retention rates. However, these programs may fall short in addressing the specific needs of NLRNs with neurodiversities (NLRN-ND). Neurodiversity (ND) encompasses Autistic Spectrum Disorder (ASD), Attention Deficit Hyperactivity Disorder (ADHD), Tourette Syndrome, and the 3 Ds – Dyslexia, Dyscalculia, and Dysgraphia. Unsupportive environments for disclosing neurodiversity and requesting accommodations may contribute to the 10-25% NLRNs leaving their jobs within the first year, with 1-3% exiting the nursing profession altogether. Objectives: This study aimed to (1) explore NLRN-ND …

Exploring Teamwork Between Virtual And Bedside Nurses, Caitlin Weinheimer

Dissertations and Theses (Open Access)

Background: Advancing technologies and the use of telehealth have expanded in hospitals to include telenursing. Telenursing introduces a unique dynamic where virtual and bedside nurses work together as a remote team to provide patient care. Published literature reports that teamwork among nurses and healthcare professionals impacts patient and workforce outcomes. However, there is a gap in exploring teamwork between virtual and bedside nurses. Addressing this knowledge gap is critical to ensure positive patient and nursing workforce outcomes in hospital-based telenursing settings.

Objective: To generate a grounded theory that explains teamwork between virtual and bedside nurses in the hospital setting. A …

Breastfeeding Education Preferences Of Pregnant People With Low Incomes, Megan Kindred

Dissertations and Theses (Open Access)

Background: The proportion of infants breastfed at 1 year in the United States remains below the Healthy People 2030 goal. Longer breastfeeding durations are important due to dose-response benefits, but disparities are greater among those with low incomes. Prenatal breastfeeding education (PBE) interventions can increase breastfeeding duration. Additionally, incentivization and gamification can be used to increase use of educational technology but are underexplored in this domain. Prior studies examining PBE format preferences do not reflect currently available technology. PBE format preferences of childbearing people should be reexamined.

Purpose: This purpose of this study is to: (1) identify PBE format preference …

Pattern Dynamics And Stochasticity Of Brain Rhythms And Spike Trains In A Tauopathy Mouse Model Of Alzheimer’S Disease, Clarissa M. Hoffman

Dissertations and Theses (Open Access)

Systems neuroscience posits that every aspect of perceived physical reality, every aspect of animal and human behavior, and every cognitive phenomenon emerges from patterns of neuronal activity. While most researchers embrace this idea, there are major difficulties in describing and analyzing these complex neuronal dynamics—spike flows produced by cells ensembles, synchronized extracellular field oscillations, and other patterns—which limits our understanding of how the activity of individual neurons and the whole-animal cognition and behavior might be connected. In particular, we lack the approaches and even the semantics for connecting the individual cell outputs and the integrated results of their activity. Current …

Technical Development, Optimization, And Clinical Implementation Of Quantitative Magnetic Resonance Imaging Methods For Radiation Oncology, Lucas Mccullum

Dissertations and Theses (Open Access)

Magnetic resonance imaging (MRI) has gradually grown more important in the field of radiation oncology. This paradigm shift has grown from initial experiments with MRI of cancerous lesions in the early 1970s, to the integration of MRI images for radiation therapy treatment planning (i.e., MRI-Simulation) in the early 1980s, to the combined MRI linear accelerator (MR-Linac) becoming commercially available in 2018 which can simultaneously image a tumor and treat it with radiation. However, due to its novelty in radiation oncology, its full potential for the integration of quantitative MRI-based biomarkers has yet to be fully realized.

Therefore, this dissertation will …

In-Vitro Testing Of Light Wavelength To Detect Clots In Neonatal Extracorporeal Membrane Oxygenation Circuitry, Amanda Holmes

Dissertations and Theses (Open Access)

Background: Neonates requiring extracorporeal membrane oxygenation (ECMO) are at high risk for thrombotic complications, which contribute substantially to morbidity and mortality. Current circuit surveillance methods rely on intermittent visual inspection and indirect laboratory markers, both of which often detect thrombosis only after clinically significant progression. Optical approaches offer a non-invasive alternative for earlier clot visualization, yet the influence of illumination wavelength on detection performance under realistic ECMO conditions remains incompletely characterized.

Methods: This study evaluated wavelength-dependent clot detection performance in a controlled in-vitro neonatal ECMO circuit model using a portable imaging prototype designed to emulate bedside workflow. Twelve independent ECMO …

Translating Evidence Into Action: Understanding How Community- Based Practitioners Make Intervention Implementation Decisions In Practice, Kristin C. Bennett

Dissertations and Theses (Open Access)

This study examined how community-based practitioners implement public health interventions in practice settings to identify gaps between existing implementation frameworks and real-world practice. Six farmers' markets in Southeast Texas served as cases to understand implementation decision-making by community-based practitioners addressing food access challenges. A qualitative case study approach was employed, using semi-structured interviews with program adopters and key stakeholders to examine how practitioners addressed food access problems, selected interventions, and navigated implementation decisions. This methodology captured the contextual nature of implementation decision-making in community settings. The findings revealed that program adopters recognized health problems through lived experience rather than formal …

Parental Experiences With Financial Toxicity In The Pediatric Intensive Care Unit: A Phenomenological Research, Sohrab Alexander Sardual

Dissertations and Theses (Open Access)

Background: Parents of children admitted to the pediatric intensive care unit (PICU) encounter multiple stressors; however, there is a need to further understand their experiences with financial toxicity. Understanding parents’ experiences and perspectives on how they can be assisted is a critical first step to formulating interventions to help parents deal with financial toxicity.

Aims: The aims of this study are (a) to describe the experiences with financial toxicity of parents with critically ill children admitted to the PICU and (b) to explore parents’ perspectives on how they can be assisted in dealing with financial toxicity.

Methods: A phenomenological qualitative …

Sik2 Inhibitor Grn-300 Enhances Sensitivity To Paclitaxel Treatment In Triple-Negative Breast Cancer, Marc A. Pina

Dissertations and Theses (Open Access)

Breast cancer is one of the most frequently diagnosed cancers worldwide, with approximately 15% classified as Triple-Negative Breast Cancer (TNBC). TNBC lacks expression of estrogen (ER) and progesterone (PR), and does not overexpress HER-2, leaving patients without effective targeted therapies. As a result, treatment primarily relies on chemotherapy, most commonly paclitaxel, a taxane that stabilize microtubules, disrupts chromosome separation and induces apoptosis. However, TNBCs are an aggressive cancer subtype, and patients often will develop resistance after a few rounds of chemotherapy. This study addresses a critical unmet need for more effective TNBC therapies by targeting Salt-Inducible Kinase 2 (SIK2), which …

Host-Intrinsic Factors Determine Anti-Tumor Efficacy Of Exercise In Pancreatic Ductal Adenocarcinoma, Sumedha Pareek

Dissertations and Theses (Open Access)

Pancreatic Ductal Adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths with a low 5-year relative survival rate of approximately 13.3% for all stages combined. We have previously shown that exercise can improve quality of life and enhance functional capacity among patients with PDAC. Exercise induces a variety of changes in the tumor microenvironment with beneficial effects in several tumor types. However, our understanding of the clinical effects of exercise and the mechanisms that mediate anti-tumor effects are limited in pancreatic cancer.

In this project, using C57BL/6 mice from Taconic Biosciences (Tac) and Jackson Laboratories (Jax), we established a …

Capsinoids, Non-Pungent Trpv1 Agonists, Induce A Mild Hypothermia That Provides Short- And Long-Term Neuroprotection After Ischemic Stroke, Alexander Andersohn, Alexander Andersohn

Dissertations and Theses (Open Access)

Therapeutic hypothermia (TH) has demonstrated neuroprotection in instances of cardiac arrest and neonatal hypoxia/ischemia but faces different challenges in application to stroke due to the activation of cold defense mechanisms in conscious patients. This dissertation examines the efficacy and specificity of capsinoids (a purified mixture of capsiate and dihydrocapsiate) to induce a sustained mild hypothermia in conscious mice that is neuroprotective after stroke. Capsinoids function as TRPV1 agonists. However, unlike capsaicin, capsinoids are vulnerable to esterase-mediated breakdown, thus significantly restricting their action to the site of delivery. We showed that capsinoids delivered intraperitoneally (IP) to mice induced a TRPV1-dependent drop …

Orthogonal Comparison Of Nuclear And Mitochondrial Clonal Architectures In Hematologic Malignancies, Nehali Shah

Dissertations and Theses (Open Access)

Acute myeloid leukemia (AML) is a hematologic malignancy characterized by accumulation of mutations that disrupt hematopoietic differentiation and promote clonal expansion. Understanding how these mutations arise and evolve is essential for improving diagnosis, prognosis, and treatment stratification. Current methods are limited by either restricted genomic coverage (targeted panels) or low throughput and high cost (in single-cell whole genome sequencing, scWGS). An emerging alternative is the use of mitochondrial DNA (mtDNA) mutations as clonal markers.

This study aims to determine whether mitochondrial-derived clonal architectures correlate with nuclear-derived clonal architectures in AML, thereby evaluating mtDNA as a scalable orthogonal tool for lineage …

The Association Of Adult Medicaid Beneficiaries’ Characteristics And Their Experience During The Covid-19 Pandemic, Frank R. Tortorella

Dissertations and Theses (Open Access)

Background: The COVID-19 pandemic disrupted the United States’ safety net program, Medicaid, for low-income individuals affecting access to care, increasing enrollment, and requiring new approaches to care delivery. The literature shows that beneficiaries’ personal characteristics influence their healthcare experience. This study investigated the association between Medicaid beneficiary characteristics and experience with their Medicaid health plan, examined if COVID-19 negatively impacted experience, and tested if COVID-19 moderated the relationship between beneficiary characteristics and experience.

Methods: The research sample was 76,976 adult Medicaid beneficiaries who voluntarily completed the annual Consumer Assessment of Healthcare Providers and Systems (CAHPS) health plan surveys in 2018 …

Dissecting The Heterogeneous Effects Of Opioid Prescribing Limit Laws On Pediatric Mortality: A Multidimensional And Negative Binomial Modeling Approach, Francine R. Vega

Dissertations and Theses (Open Access)

Opioid prescribing for children and adolescents continues to be a significant health crisis in the United States. Early naïve exposure to opioid prescriptions has been linked to later misuse, opioid use disorder, and death. In response to the crisis, many states have implemented opioid prescribing limit laws (OPLLs) aimed at reducing exposure to opioids. These laws vary widely in their approach, including differences in dosage restrictions, prescription duration limits, informed consent requirements, educational provisions, and whether they offer explicit protections specifically for minors. Despite their widespread adoption, there is limited understanding of how heterogeneity in legal regulations affects outcomes for …

Rethinking Health Systems Responsiveness In Low–And Middle-Income Countries, Meesha Iqbal

Dissertations and Theses (Open Access)

Health systems responsiveness (HSR) refers to a health system’s ability to meet legitimate non-health expectations of the population. Traditionally, HSR has been conceptualized across eight domains: respect for dignity, autonomy, confidentiality, prompt attention to health needs, availability of basic amenities, choice of provider, access to social support networks, and clarity of communication. However, as the expectations of populations in high-income countries (HICs) and low- and middle-income countries (L&MICs) differ significantly due to diverse social and cultural contexts, the conceptualization of HSR also varies. We conducted a systematic review of literature to adapt and contextualize the HSR framework for L&MICs based …

Anxiety During Perimenopause: A Narrative Qualitative Study Of The Women’S Lived Experiences, Kayla Mcelhany

Dissertations and Theses (Open Access)

Abstract

Objectives: Perimenopause has been associated with increased anxiety symptoms. However, data is lacking regarding the experiences of women with perimenopausal anxiety and the contributing factors to worsening anxiety symptoms. We explored the experiences of women with self-reported new onset or worsening of anxiety symptoms during perimenopause to better understand contributing factors.

Study design: Twenty women participated in one-on-one interviews to explore experiences of perimenopausal anxiety in the context of their daily lives and perimenopausal physical changes. Inductive thematic analysis was used to develop codes and themes from the transcribed interview data. Analysis was done using MAXQDA software.

Main …

Integrating Bulk And Single-Cell Transcriptomics To Investigate Intratumor Heterogeneity, Shuai Guo

Dissertations and Theses (Open Access)

Cancers are heterogeneous mixtures of tumor and surrounding cells, where each component comprises multiple distinct sub-types and/or states. Understanding the cell-type-specific contributions is critical for advancing cancer biology, yet high-throughput expression profiles from tumor tissues only represent combined signals from all diverse cellular sources. Bulk deconvolution with single-cell/nucleus (sc/sn) RNA-seq data has emerged as a powerful approach to dissect both cellular composition and cell-type-specific expression patterns, yet the technological discrepancy across sequencing platforms limits accuracy.

To systematically evaluate the impact of platform discrepancies on bulk deconvolution, we first generated a benchmark dataset of 24 healthy retinas with paired bulk and …

Effects Of Sex And Aging In The Response To Global Cerebral Hypoperfusion, Alexis Mcalister

Dissertations and Theses (Open Access)

Introduction

The prevalence of dementia worldwide is projected to double by the year 2030 and triple by 2050. Vascular cognitive impairment and dementia (VCID) encompasses diseases that lead to cognitive decline and dementia due to cerebrovascular disease. VCID is the second most common form of dementia after Alzheimer’s disease, accounting for approximately 15- 40% of all dementia cases. Reductions in cerebral blood flow from intracranial and extracranial atherosclerosis increase VCID risk, even in the absence of overt clinical or imaging evidence of stroke/embolization. The pathology seen in patients with chronic cerebral hypoperfusion, such as inflammation, neuronal loss, white matter abnormalities, …

Microbial Metabolite Regulation Of Microglial Ahr Signaling In Alzheimer’S Disease, Ghalya E. Alrousan

Dissertations and Theses (Open Access)

Introduction: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β plaque accumulation, neuroinflammation, and cognitive decline. Recent evidence suggests that systemic factors, particularly the gut microbiota and its metabolites, play a significant role in shaping brain immune responses, including microglial activation. However, the mechanisms linking gut dysbiosis to microglial dysfunction in AD are poorly understood. The aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor responsive to tryptophan metabolites, has recently gained attention as a key regulator of neuroinflammation and microglial function. I hypothesize that the loss of beneficial microbial AHR ligands, specifically indole derivatives, during aging and AD …

Modeling Buprenorphine Treatment Discontinuation In Opioid Use Disorder – Predictors And Disparities Using Statistical And Machine Learning Approaches, Wanru Guo

Dissertations and Theses (Open Access)

Background: Opioid Use Disorder (OUD) remains a major public health crisis in the U.S., and while buprenorphine is an effective treatment, early discontinuation undermines its impact. Existing statistical and machine learning (ML) models often overlook key social and healthcare-related predictors and fail to capture subgroup disparities, limiting their utility for equitable intervention design. This study addresses these gaps using a nationwide, longitudinal dataset and a two-stage modeling approach focused on disparity identification. Methods: We analyzed buprenorphine treatment episodes for OUD from the IQVIA Pharmetrics Plus database (2006–2023), defining discontinuation as episodes lasting under 180 days. A Cox proportional hazards model …

Artificial Intelligence (Ai)-Assisted Cardiotoxicity Management In Lung Cancer Radiotherapy, Xinru Chen

Dissertations and Theses (Open Access)

Lung cancer remains one of the leading causes of cancer-related mortality worldwide, with radiation therapy being a cornerstone of treatment. However, radiation-induced cardiotoxicity has emerged as a significant long-term complication, impacting patient survival and quality of life. There is increasing evidence that post-radiotherapy cardiotoxicity is better indicated by cardiac substructure dose, compared with whole heart dose. Despite this, cardiac substructures are not routinely incorporated into clinical workflows due to the significant time and resource demands associated with manual segmentation. Moreover, the relationship between dose distribution in radiotherapy plans and radiation-induced cardiotoxicity remains incompletely understood. Therefore, the development of an automated …

Fc Gamma Receptors Facilitate Antigenic Modulation Of Lilrb4 And Function As Predictive Biomarkers In Acute Monocytic Leukemia, Joshua Morse

Dissertations and Theses (Open Access)

Acute monocytic leukemia (monocytic AML) is a subtype of AML marked by a proliferation of abnormal monoblasts. This subtype represents approximately 10% of AML cases. The prognosis of monocytic AML is poor, with a 5-year survival of ~30%. Most patients are diagnosed at an age when they are unlikely to survive first-line non-targeted cytotoxic chemotherapy as a bridge to hematopoietic stem cell transplant (HSCT). Even patients who achieve remission commonly relapse. This population of patients would greatly benefit from precision-targeted therapies but currently there are none approved for monocytic AML.

Leukocyte immunoglobulin-like receptor B4 (LILRB4) is an immune checkpoint expressed …

Expanding Inducible Epithelial Resistance Against Pneumonia: Novel Virus, Novel Receptor, Michael Longmire

Dissertations and Theses (Open Access)

Pneumonia is the leading infectious cause of death worldwide and presents a continuing risk among immunocompromised patients. Our work has been focused for many years on the phenomenon of inducible epithelial resistance, where activation of the innate immune response in the airway epithelium is necessary and sufficient to produce a pathogen-killing but self-protective environment to prevent severe disease. Inducible resistance is pathogen-agnostic and has been demonstrated against an array of respiratory infections. We achieve this using a combination of pattern recognition receptor agonists – Pam2CSK4 and ODN M362 being the current formulation – which produce synergistic levels of pathogen reduction …

The Role Of Ucp2 In Pancreatic Cancer Metabolism And Its Potential As A Radiosensitizer, Emily Rieff

Dissertations and Theses (Open Access)

Uncoupling protein 2 (UCP2) is a mitochondrial protein that regulates the flow of protons down the gradient established by the electron transport chain (ETC) without generating ATP, thus uncoupling the proton gradient from ATP generation. In tumors, specifically pancreatic cancer (PDAC), the ETC is highly stimulated to generate the copious ATP needed by the tumor to grow. However, extended ETC use increases reactive oxygen species (ROS), and if left unchecked, results in cell death. To evade this, PDAC employs antioxidant strategies, including upregulating UCP2 in tumor cells. In addition to its uncoupling function, UCP2 indirectly controls ROS levels by maintaining …

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 …

Immune Landscape Of Early Liver Metastatic Lesions In A Novel Immunocompetent Murine Colorectal Cancer Metastasis Model, Alaa Mohamed

Dissertations and Theses (Open Access)

Colorectal cancer minimal residual disease (MRD) represents a major clinical problem for colorectal cancer patients, with failure rates of surgery and adjuvant chemotherapy between 5% to 40% depending on stage of disease. In our study, we simulated MRD using genetically engineered organoids with precise somatic editing of APC and TP53, creating a murine model that mimics human liver metastatic colorectal cancer. By implementing a meticulously timed experimental metastatic model, we could detect microscopic tumor lesions. Through genomic and transcriptomic analyses, we pinpointed the importance of macrophages, particularly those expressing high levels of CSF1R, in these microscopic metastatic focal lesions. We …