Life Sciences Commons^™

In-Hospital Mortality Patterns And Readmissions In Patients With Chronic Obstructive Pulmonary Disease: An Analysis Of The Role Of Pulmonary Hypertension, Saad Afzal Khan, Trishna Parikh, Adishwar Rao, Akriti Agrawal, Aarohi Parikh, Farah Kazzaz, Sarah Shin, Harry Karmouty-Quintana, Maulin Patel, Kha Dinh, Bela Patel, Bindu Akkanti

Faculty, Staff and Student Publications

Chronic obstructive pulmonary disease (COPD) may be complicated by pulmonary hypertension (PH). We aimed to understand the impact of PH on in-hospital mortality and quantify the 30-day readmission rate among patients with COPD. For this cross-sectional study, we used the Nationwide Readmissions Database from 2017-2020 to identify adults ≥18 years with COPD. Patients were stratified according to PH diagnosis. Baseline characteristics between groups were compared using the Pearson chi-square test and two-sample t-test. Predictors of in-hospital mortality were determined using multivariate logistic regression analysis adjusted for demographics and confounders. The 30-day readmission rate and prevalence of PH subgroups by baseline …

Staphylococcus Aureus Urease Is Controlled By A Complex Regulatory Network To Promote Dissemination During Cauti, Jana Gomez, Jesus Duran-Ramirez, Maristhela Alvarez, Shane Cristy, Jennifer N Walker

Faculty, Staff and Student Publications

Catheter-associated urinary tract infections (CAUTIs) are one of the most common hospital-associated infections in the United States, accounting for >1 million cases annually. One CAUTI pathogen, Staphylococcus aureus, is commonly found persisting asymptomatically in the bladder of catheterized individuals, increasing these individuals' risk of developing infection. Importantly, S. aureus is not only associated with severe symptoms during CAUTI, including bacteremia and septic shock, but it also produces a common uropathogen-associated virulence factor, urease. Despite its importance, urease has only been well-studied in another uropathogen, Proteus mirabilis. While previous studies identified three S. aureus urease regulators, including CodY, …

Genetic Regulation Of Uterine Organogenesis, Diana A. Machado

Dissertations and Theses (Open Access)

In eutherian and marsupial mammals, the site of embryo implantation and gestation is the uterus. The precursor tissue of the uterus, oviducts, cervix, and upper vagina is the Müllerian duct epithelium and its adjacent mesenchyme. Morphological uterine variation between species is established during embryogenesis by species-specific differences in Müllerian duct fusion at the midline, growth, and differentiation. For example, laboratory mice have a bipartite uterus with two uterine horns and a single cervix, whereas humans have a simplex uterus with a single chamber and single cervix. In humans, variations in the fusion process can alter typical uterine morphology, correlating with …

Function And Regulation Of Long Polar Fimbriae During Enterohemorrhagic Escherichia Coli Infection, Walter J. Galdamez

Dissertations and Theses (Open Access)

Enterohemorrhagic Escherichia coli (EHEC) is a foodborne pathogen that causes severe gastrointestinal disease and hemolytic uremic syndrome. EHEC employs multiple virulence factors to colonize the host intestine, including the locus of enterocyte effacement (LEE) encoded type III secretion system, intimin, and flagella, yet the role of long polar fimbriae (Lpf) in adhesions and infection remains less well understood. Long polar fimbriae can mediate bacterial attachment to host cells in vitro, yet the regulation and function of its two fimbrial operons, lpf1 and lpf2 in vivo remain poorly understood. Preliminary RNA-seq data from zebrafish infected with EHEC reveal that expression of …

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 …

Transcriptional Regulation In The Uterine Luminal Epithelium, Evelyn A. Carrion

Dissertations and Theses (Open Access)

Transcriptional Regulation in the Uterine Luminal Epithelium

Evelyn A. Carrion

Advisor: Richard R. Behringer, PhD

Abstract

The uterus is an organ comprised of multiple tissues that are essential for women’s health and reproduction. The uterus is composed of multiple tissue layers, including the perimetrium, myometrium, and the endometrium. The endometrium is the inner lining of the uterus, and contains the luminal epithelium, glandular epithelium, and stroma. The luminal epithelium is a simple columnar layer of cells that is necessary for embryo implantation. The uterus is derived in part from the embryonic precursor tissue called the Müllerian duct. There are no …

Defining The Role Of Spxa1 And Spxa2 In Group A Streptococcus (Gas), Gretchen Anne Morrison

Dissertations and Theses (Open Access)

Group A Streptococcus (GAS) is a human-restricted pathogen whose global incidence has surged in the post-COVID era. The ability of GAS to shift from a colonizing to invasive phenotype depends on coordinated virulence gene regulation in response to host-imposed stressors. The paralogous global transcriptional regulators, SpxA1 and SpxA2, have emerged as central mediators of these adaptive responses; however, the mechanisms by which these regulators influence both global gene regulation in direct response to external stresses and the host response as a result of regulatory changes remain incompletely understood. Using an integrated multi-omic approach, we define the distinct yet interconnected regulatory …

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 …

Oxidative Stress Mediated Glutamate Release And Nmda Receptor-Dependent Synaptic Remodeling In Radiation-Induced Cognitive Dysfunction, Thanh Lam

Dissertations and Theses (Open Access)

In children younger than 14 years old, the brain and other parts of the central nervous system are the most common sites for solid tumors. Radiotherapy is an effective treatment for central nervous system (CNS) tumors. However, it often causes a progressive decline in cognitive functions, which is especially devastating for pediatric patients. Although post-mitotic neurons are generally considered resistant to radiation-induced immediate cell death, ionizing radiation causes complex neurochemical and structural changes that damage synaptic integrity. In this study, we examined the molecular cascades following a 10 Gy radiation dose applied to mouse cortical neurons. We found that radiation-induced …

Mutational Analysis Of Domain Functions In The Yeast Decapping Enzyme Dcp2, Jellisa Ewan, Ambro Van Hoof

Dissertations and Theses (Open Access)

In yeast, the major mRNA decay pathway involves deadenylation of the 3’ poly-A tail, followed by decapping of the 5’ m7Gppp cap and subsequent 5’ to 3’ degradation or 3’ to 5’ degradation. This is carried out by Pan2/Pan3 and Ccr4/Not deadenylases, the decapping enzyme Dcp2, and Xrn1 and  RNA exosome exoribonucleases, respectively. The eukaryotic mRNA decapping enzyme complex, Dcp1/Dcp2, is essential in yeast, and deletion of either gene is lethal. However, the deadenylases that act upstream and the 5’ exoribonuclease that act downstream of the decapping step are not, even though they are all highly conserved with no known …

From Geometry To Recognition: A Quantitative Framework For Tcr-Pmhc Structural Analysis In The Age Of Predicted Structures, Kun Hee Kim

Dissertations and Theses (Open Access)

Recognition of antigen by a T cell begins with a single physical event, the engagement of the T cell receptor (TCR) with a peptide-major histocompatibility complex (pMHC), and this interaction is encoded in the geometry with which the receptor docks onto the composite pMHC surface. Whether that docking geometry is biologically organized, and whether the structures now produced at scale by prediction preserve recognition or only reproduce that organization, are the two questions this thesis addresses. Two gaps stand in the way. The first is a gap of measurement, because docking geometry has never been made quantitatively comparable across many …

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 …

Nmda Receptor Subunit Nmr-2 Regulates Pathogen-Induced Immune Responses Via The Nervous System In C. Elegans, Benson Otarigho, Jonathan Lalsiamthara, Alejandro Aballay

Faculty, Staff and Student Publications

Neural control of innate immunity must balance restraint of basal immune activity with rapid activation upon pathogen encounter. Glutamate, the primary excitatory neurotransmitter in the nervous system, has been implicated in several neurological disorders associated with inflammation, suggesting a potential link to immune regulation. However, how glutamatergic signaling contributes to immune balance remains unknown. Here, we demonstrated that the NMDA-type ionotropic glutamate receptor subunit NMR-2, a component of the NMDA receptor complex, acts in the

Ldm-Morph: Latent Diffusion Model Guided Deformable Image Registration, Jiong Wu, Tinsu Pan, Kuang Gong

Faculty, Staff and Student Publications

Deformable image registration plays an essential role in various medical image tasks. Existing deep learning-based deformable registration frameworks primarily utilize convolutional neural networks (CNNs) or Transformers to learn features to predict the deformations. However, the lack of semantic information in the learned features limits the registration performance. Furthermore, the similarity metric of the loss function is often evaluated only in the pixel space, which ignores the matching of high-level anatomical features and can lead to deformation folding. To address these issues, in this work, we proposed LDM-Morph, an unsupervised deformable registration algorithm for medical image registration. LDM-Morph integrated features extracted …

Exploring Csf Microrna Signatures As Diagnostic Biomarkers In Adult-Type Diffuse Gliomas, Maryam Pirhoushiaran, Kamilah Walker-Charles, Tsung-Hung Yao, Satwikreddy Putluri, Nehal Patel, Daniel H Wang, Isabel Wang, Srividya Arjuna, Antonio Dono, Angel Bueno, Sophia Nguyen, Ashish P Balar, Jason T Huse, Suprateek Kundu, Yoshua Esquenazi, Chirag B Patel, Sujit S Prabhu, Frederick F Lang, Leomar Y Ballester

Faculty, Staff and Student Publications

Mutations in isocitrate dehydrogenase (IDH) genes, specifically IDH1 and IDH2, are frequently observed in diffuse gliomas (DG) and define distinct molecular subtypes, namely IDH-wildtype and IDH-mutant. Abnormal expression of extracellular vesicle-derived microRNAs (EV-miRNAs) in the cerebrospinal fluid (CSF) of DG patients may serve as minimally invasive diagnostic and prognostic biomarkers. To investigate this potential, we employed miRNA-sequencing (miRNA-seq), quantitative real-time PCR (qRT-PCR), and multivariable logistic regression (MLR) to identify differentially expressed microRNAs (DE-miRNAs) in CSF samples from DG patients. qRT-PCR analysis demonstrated that EV-miR-21-5p effectively differentiated CSF from glioblastoma (GBM) patients versus controls (p = 0.012, AUC = 0.84) and …

Nlrp3 Inflammasome: A Link Between Systemic Infection And Alzheimer’S Disease, Tatiana Barichello, Felipe Dal-Pizzol

Faculty, Staff and Student Publications

No abstract provided.

Exploring Csf Microrna Signatures As Diagnostic Biomarkers In Adult-Type Diffuse Gliomas, Maryam Pirhoushiaran, Kamilah Walker-Charles, Tsung-Hung Yao, Satwikreddy Putluri, Nehal Patel, Daniel H Wang, Isabel Wang, Srividya Arjuna, Antonio Dono, Angel Bueno, Sophia Nguyen, Ashish P Balar, Jason T Huse, Suprateek Kundu, Yoshua Esquenazi, Chirag B Patel, Sujit S Prabhu, Frederick F Lang, Leomar Y Ballester

Faculty, Staff and Student Publications

Mutations in isocitrate dehydrogenase (IDH) genes, specifically IDH1 and IDH2, are frequently observed in diffuse gliomas (DG) and define distinct molecular subtypes, namely IDH-wildtype and IDH-mutant. Abnormal expression of extracellular vesicle-derived microRNAs (EV-miRNAs) in the cerebrospinal fluid (CSF) of DG patients may serve as minimally invasive diagnostic and prognostic biomarkers. To investigate this potential, we employed miRNA-sequencing (miRNA-seq), quantitative real-time PCR (qRT-PCR), and multivariable logistic regression (MLR) to identify differentially expressed microRNAs (DE-miRNAs) in CSF samples from DG patients. qRT-PCR analysis demonstrated that EV-miR-21-5p effectively differentiated CSF from glioblastoma (GBM) patients versus controls (p = 0.012, AUC = 0.84) and …

Potential Impact Of Parasites In The Transmission Of Chronic Wasting Disease, Paulina Soto, Rodrigo Morales

Faculty, Staff and Student Publications

No abstract provided.

Effects Of M6a Dna Methylation By Bacterial Methyltransferase In Colorectal Cancer, Fabian Alejandro Mendoza Galvan

Dissertations and Theses (Open Access)

Effects of m6A DNA methylation by bacterial methyltransferase in colorectal cancer Fabian Alejandro Mendoza Galvan Advisory Professor: Angela H. Ting, Ph.D. Fusobacterium nucleatum animalis (Fna) is found in the human oral cavity and gut. A distinct clade of Fna is primarily enriched in the tumor microenvironment (TME) and within colorectal cancer (CRC) cells. This clade DNA methylation pattern is primarily catalyzed by a cell-cycle regulated methyltransferase (CcrM) ortholog, M.FnI, that targets the GANTC sequence motif through methyl-6-Adenine (m6A) DNA methylation. We hypothesized that M.FnI enzyme can induce m6A methylation abnormalities in CRC cells to promote cancer progression. Evidence for endogenous …

A Tractable Nematode Model For The Emerging Fungal Pathogen, Candida Auris, Melissa Martinez

Dissertations and Theses (Open Access)

Candida auris is an emerging multidrug-resistant opportunistic fungal pathogen. It

poses a significant threat to immunocompromised patients and those with prolonged stays in

healthcare facilities. C. auris spreads rapidly in health care facilities through enhanced

colonization of skin and abiotic surfaces. The genetic factors contributing to this ability and to

the virulence, drug resistance, and stress-tolerant nature of C. auris are largely unknown.

Current animal models of C. auris infections are not well standardized and report conflicting

results. Additional animal models of virulence are needed, especially those amenable to high-

throughput analysis. The nematode Caenorhabditis elegans has been validated as …

Targeting Breast Cancer Brain Metastasis Through Novel Combination Of Fda-Approved Orally Active Blood-Brain Barrier Permeable Ret And Tgli1 Inhibitors, Joshua Cha

Dissertations and Theses (Open Access)

Breast cancer is the most diagnosed cancer in American women, and breast cancer brain metastasis (BCBM) exhibits the worst prognoses with a life-expectancy averaging at 6 months. This short life expectancy is largely attributed to the lack of effective treatment. Many challenges remain unsolved, including the limited number of actionable targets for targeted therapy and effective blood-brain barrier (BBB) permeable drugs that are safe without promoting drug resistance. Therefore, there is an urgent call for identification of novel therapeutic targets and development of BBB-permeable drugs. One of the potential targets identified by our lab for BCBM targeted therapy is the …

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 …

Characterization Of Staphylococcus Aureus Clinical Isolates From Deep Musculoskeletal Infections For An In Vitro Biofilm Model For Phage Therapy, Raquel C. Luna

Dissertations and Theses (Open Access)

The rise of multidrug-resistant (MDR) infections is a growing concern in the treatment of deep musculoskeletal infections (MSKIs) and orthopaedic device-related infections (ODRIs). Staphylococcus aureus is responsible for about one third of these infections due to its strong biofilm forming capacity, presence on human skin, and the large number of antibiotic-resistant variants. Bacteriophage (phage) therapy is now being considered as a treatment for MDR MSKIs/ODRIs. We are investigating the use of phage encapsulated into or adsorbed onto biodegradable microspheres for local delivery to the site of these MDR infections. We determined that the anti-staphylococcal phage K effectively lyses the S. …

From Antigen Presentation To Tumor Control: Mechanisms Of Type I Conventional Dendritic Cell-Based Cancer Vaccines, Josue E. Pineda

Dissertations and Theses (Open Access)

Type 1 conventional dendritic cells (cDC1s) are important for generating and sustaining antitumor immunity. Accordingly, the abundance of cDC1s in human tumors correlates with improved outcomes in cancer. Capitalizing on this role, we previously demonstrated that vaccination with in vitro-derived murine cDC1s elicits durable tumor control in multiple preclinical models; however, the immunological mechanisms underlying the efficacy of cDC1 vaccination remain unclear. Here, we examined whether in vitro-derived cDC1s resemble tumor-infiltrating DC populations and whether MHC-I and MHC-II antigen presentation contribute to cDC1-mediated tumor control following vaccination in melanoma.

As expected, MHC-I- or MHC-II-deficiency had minimal impact on …

Membrane Organization Of Rheb And Rhoa: Roles In Function And Allosteric Druggability, Chase M. Hutchins

Dissertations and Theses (Open Access)

Small GTPases of the Ras superfamily are membrane-bound molecular switches that regulate nearly all major cellular processes, and their dysregulation drives cancers, neurological disorders, and metabolic diseases. While anchored to cellular membranes, the catalytic domains of small GTPases undergo orientation dynamics, adopting distinct configurations that can occlude or expose effector-binding surfaces and modulate signaling output. These dynamics have been characterized in the Ras oncoproteins, but whether they extend across the superfamily and influence allosteric druggability has remained unknown.

In this dissertation, I address these questions through Rheb and RhoA, two small GTPases with complementary differences in subfamily lineage, membrane localization, …

Understanding Epigenomic Landscapes In Cancer Progression And Immunotherapy Response, Jonathan Schulz

Dissertations and Theses (Open Access)

Nonmutational epigenomic reprogramming has emerged as a key hallmark of cancer that plays crucial roles in tumor evolution during its progression and response to therapy. However, the extent and nature of epigenomic reprogramming remains poorly understood. This dissertation examines how epigenetic regulation shapes cancer progression and response to immunotherapy. Working at the intersection of cancer biology and computational genomics, it develops analytical frameworks for characterizing chromatin structure and DNA methylation across diverse tumor contexts and uses these frameworks to address two complementary biological questions: how promoter-associated chromatin organization varies across cancer types, and how epigenetic perturbation modulates tumor immunogenicity in …

Optimized Ultrasound Imaging Of Phase-Change Nanodroplets, Charles R Dyall, Dmitry Nevozhay, Andy Liu, Trevor M Mitcham, George J Lu, Konstantin V Sokolov, Richard R Bouchard

Faculty, Staff and Student Publications

Phase-change nanodroplets (PCNDs) continue to generate significant research interest due to their potential to extravasate into tissue, to be targeted for molecular imaging and drug delivery, and to undergo an induced phase-change to "activated" microbubbles (MBs) for ultrasound (US) imaging. To accurately quantify molecular markers, however, one assumes a consistent proportion of PCNDs in a region of interest (ROI) are stably activated and imaged. Herein we present a framework for developing a diagnostic sequence that is optimized for PCND activation uniformity, contrast, and acquisition time. To develop this framework, activation was examined at three scales of increasing complexity: single, adjacent, …

Corrigendum To 'Risk Factors For Bronchiolitis Obliterans Syndrome After Initial Detection Of Pulmonary Impairment After Hematopoietic Cell Transplantation' [Transplantation And Cellular Therapy 29/3 (2023) 204-204], Mansour Alkhunaizi, Badar Patel, Luis Bueno, Neel Bhan, Tahreem Ahmed, Muhammad H Arain, Rima Saliba, Gabriela Rondon, Burton F Dickey, Lara Bashoura, David E Ost, Liang Li, Shikun Wang, Elizabeth Shpall, Richard E Champlin, Rohtesh Mehta, Uday R Popat, Chitra Hosing, Amin M Alousi, Ajay Sheshadri

Faculty, Staff and Student Publications

No abstract provided.

Growth Hormone Pathway As A Prognostic And Therapeutic Biomarker In Patients With Unresectable Hepatocellular Carcinoma Treated With Radiation Therapy, Joe R Eid, Safa Kaseb, Lianchun Xiao, Ryan Sun, Mahesh Kumar Kannan, Manal Hassan, Asif Rashid, Hop S Tran Cao, Hesham M Amin, Eugene J Koay

Faculty, Staff and Student Publications

Purpose: Radiation therapy (RT) has emerged as an effective local therapy option for patients with unresectable hepatocellular carcinoma (HCC) and is associated with improved overall survival (OS). However, some patients still have poor outcomes after RT, and biomarkers are needed to stratify prognostic groups. High circulating growth hormone (GH) levels promote HCC proliferation and survival and are associated with aggressive disease. In this study, we evaluated whether pretreatment GH levels are associated with OS and progression-free survival (PFS) in patients who underwent RT for unresectable HCC.

Methods and materials: Patients undergoing RT for HCC during 2017-2023 were identified from a …

A Multidomain Peptide Hydrogel-Liposome Composite For Controlled Release Of A Cyclic Dinucleotide In Oral Cancer, Joseph W R Swain, Andrea H Molina, Gemalene M Sunga, Danielle Chew-Martinez, Neeraja Dharmaraj, Alejandra Cobos Perez, Arghadip Dey, Ephraim J Vázquez-Rosado, Simon Young, Jeffrey D Hartgerink

Faculty, Staff and Student Publications

While immunotherapy is a promising treatment strategy for cancer, the majority of head and neck squamous cell carcinoma (HNSCC) patients treated with single-agent immunotherapy do not respond. Therefore, researchers are investigating combination treatments with immunostimulatory molecules that can maximize anti-tumor responses. Cyclic dinucleotides (CDNs) are STING agonists that hold promise in combination approaches, but they require frequent intratumoral administration when used in both preclinical models of HNSCC and clinical trials. To reduce administration frequency, we have created a peptide hydrogel–liposome composite system, K2-Lip(CDN), for local and prolonged availability of CDN. We investigated the loading limits of cationic liposomes in both …