Medical Cell Biology Commons^™

Resilience And Reality: Exploring The Lived Experiences Of People Living With Hiv In Texas During The Covid-19 Pandemic – A Qualitative Study., Ahmed F. Alanazi

Social Work Dissertations - Archive

This study investigated the lived experiences of individuals living with HIV (PLWH) in the Dallas-Fort Worth (DFW) area of Texas during the COVID-19 pandemic, using an Interpretative Phenomenological Analysis (IPA) framework. The research examined the intersection of health, social dynamics, and psychological resilience among PLWH, who faced compounded vulnerabilities due to systemic inequities and the dual public health crises of HIV and COVID-19. Through semi-structured interviews with ten participants from diverse backgrounds, the study captured the profound impacts of disrupted healthcare systems, heightened stigma, and social isolation on this marginalized population. The findings reveal that the pandemic exacerbated existing inequities …

Xanthine Oxidoreductase, Uric Acid, And Iron Homeostasis: Discovering A Therapeutic Vulnerability In Breast Cancer, Matthew G. Chapa

Graduate Theses, Dissertations, and Problem Reports (ETD)

Breast cancer remains the most frequently diagnosed malignancy and the leading cause of cancer related deaths in women. This is primarily due to distant metastases, which highlight the necessity to understand factors that contribute to breast cancer progression. Emerging evidence associates decreased tumor xanthine oxidoreductase (XOR) expression with a poorer prognosis, increased recurrence, and a more aggressive phenotype. While healthy liver, intestines, kidneys, and breast tissue have robust XOR expression and activity, there is a tendency for this to be ablated in carcinogenesis. This dissertation investigates XOR's role in breast cancer and identifies its product, uric acid (UA), as possessing …

Characterizing A Rad23 Dependent Ultraviolet Radiation Resistance In Tetrahymena Thermophila, Emma June Liimatta

Graduate Theses/Dissertations

In 2020, 10 million deaths were attributed to cancer, with multidrug resistance being responsible for over 90% of deaths in cancer patients receiving treatment. This study utilized the model organism Tetrahymena thermophila to study how cells become resistant to Ultraviolet Radiation (UV) radiation, a process similar to multidrug resistance, specifically focusing on the nucleotide excision repair and ubiquitin shuttle protein Rad23. The National Cancer Institute documented 30-60% of cancers tested had a mutation in RAD23. Knockdown of RAD23 in Tetrahymena thermophila demonstrated a UV resistance phenotype with decreased nucleotide excision repair and differential expression of proteins active within caspase-independent …

Facilitation Of Chemotherapy Efficacy Through Targeted Drug Delivery In Lung Cancer Cells Via Ultrasound And Implications On Health Interventions, Ibrahim Nasim

Honors Undergraduate Theses

Lung Cancer (small cell and non-small cell) is the leading cause of cancer death in the US, accounting for about 20% of all cancer deaths. Paclitaxel (PTX) is a chemotherapeutic agent commonly used to treat lung cancer. It works by slowing and stopping cancer growth by stiffening microtubules within cells, promoting mitotic halt and cell death. Carboplatin (CP) is another agent given to lung cancer patients containing platinum and works via direct damage of oncolytic DNA. The exact mechanism of how PTX and CP cause cell death is still an under-studied area. This thesis aims to provide insight into how …

Transposable Element Activity Captures Human Pluripotent Cell States, Florencia Levin-Ferreyra, Srikanth Kodali, Yingzhi Cui, Alison R S Pashos, Patrizia Pessina, Justin Brumbaugh, Bruno Di Stefano

Faculty, Staff and Students Publications

Human pluripotent stem cells (hPSCs) exist in multiple, transcriptionally distinct states and serve as powerful models for studying human development. Despite their significance, the molecular determinants and pathways governing these pluripotent states remain incompletely understood. Here, we demonstrate that transposable elements act as sensitive indicators of distinct pluripotent cell states. We engineered hPSCs with fluorescent reporters to capture the temporal expression dynamics of two state-specific transposable elements, LTR5_Hs, and MER51B. This dual reporter system enables real-time monitoring and isolation of stem cells transitioning from naïve to primed pluripotency and further towards differentiation, serving as a more accurate readout of pluripotency …

The Dna Demethylase Tet1 Modifies The Impact Of Maternal Folic Acid Status On Embryonic Brain Development, Lehua Chen, Bernard K Van Der Veer, Qiuying Chen, Spyridon Champeris Tsaniras, Wannes Brangers, Harm H M Kwak, Rita Khoueiry, Yunping Lei, Robert Cabrera, Steven S Gross, Richard H Finnell, Kian Peng Koh

Faculty, Staff and Students Publications

Folic acid (FA) is well known to prevent neural tube defects (NTDs), but we do not know why many human NTD cases still remain refractory to FA supplementation. Here, we investigate how the DNA demethylase TET1 interacts with maternal FA status to regulate mouse embryonic brain development. We determined that cranial NTDs display higher penetrance in non-inbred than in inbred Tet1−/− embryos and are resistant to FA supplementation across strains. Maternal diets that are either too rich or deficient in FA are linked to an increased incidence of cranial deformities in wild type and Tet1+/− offspring and to …

Promotion Of Hiv Clearance By Sensitization Of Hiv Reservoirs To Cell Death, Min Li, Baichao Sun, Jing Dong, Jian-Rong Li, Laurie J Minze, Min Chen, Chao Cheng, Jin Wang

Faculty, Staff and Students Publications

Introduction: HIV integrates its proviral DNA into the host genome to establish persistent infection. To promote HIV clearance, we have designed an approach for selective elimination of host cells harboring replication-competent HIV (SECH), through inhibition of autophagy and anti-apoptotic molecules during viral reactivation. SECH approach can clear HIV-infected cells in approximately 50% humanized mice. However, the mechanisms for the resistance of reservoirs to depletion in mice with failure in HIV clearance are unclear.

Methods: We have performed single cell transcriptome analyses of HIV-infected T cells that escaped the treatments, in order to identify cellular pathways that could be targeted to …

Tobacco Exposure Linked To Warthin’S Tumor Being The Most Common Benign Parotid Neoplasm In Veterans: A Retrospective Cohort Study, Louis Abarca, Linda K Green, Ray Y Wang, Vlad C Sandulache, David J Hernandez

Faculty, Staff and Students Publications

Objective: Parotid gland neoplasms account for a large proportion of benign salivary gland tumors, with pleomorphic adenomas (PA) being the most common in the civilian population, followed by Warthin's tumor (WT). However, the distinct risk profiles of Veterans significantly influence the incidence and prevalence of salivary gland neoplasms. We investigated the diagnostic and management algorithms for benign parotid gland neoplasms in Veterans.

< >Methods: Retrospective cohort study. Descriptive statistics were calculated using Microsoft Excel. Categorical variables were compared using chi square tests, and were reported with 95% confidence intervals, with statistical significance set at P <  .05.

Results: The study included 158 patients …

Inhibition Of Ribosome Biogenesis In Vivo Causes P53-Dependent Death And P53-Independent Dysfunction, Charles J Cho, Thanh Nguyen, Amala K Rougeau, Yang-Zhe Huang, Sarah To, Xiaobo Lin, Supuni Thalalla Gamage, Jordan L Meier, Jason C Mills

Faculty, Staff and Students Publications

Background & aims: Although it is well-known that ribosomes are critical for cell function, and their synthesis (known as ribosome biogenesis [RiBi]) is energy-intensive, surprisingly little is known about RiBi in vivo in adult tissue.

Methods: Using a mouse model with conditional deletion of Nat10, an essential gene for RiBi and subsequent translation of mRNA, we investigated the effects of RiBi blockade in vivo, with a focus on pancreatic acinar cells during homeostasis and tumorigenesis.

Results: We observed an unexpected latency of several weeks between Nat10 deletion and onset of structural and functional abnormalities and p53-dependent acinar cell death. Although …

Reliable Rna-Seq Analysis From Ffpe Specimens As A Means To Accelerate Cancer-Related Health Disparities Research, Mitchell J Frederick, Dannelys Perez-Bello, Pedram Yadollahi, Patricia Castro, Alan Frederick, Andrew Frederick, Rashid A Osman, Fonma Essien, Imelda Yebra, Ashley Hamlin, Thomas J Ow, Heath D Skinner, Vlad C Sandulache

Faculty, Staff and Students Publications

Whole transcriptome sequencing (WTS/ RNA-Seq) is a ubiquitous tool for investigating cancer biology. RNA isolated from frozen sources limits possible studies for analysis of associations with phenotypes or clinical variables requiring long-term follow-up. Although good correlations are reported in RNA-Seq data from paired frozen and formalin fixed paraffin embedded (FFPE) samples, uncertainties regarding RNA quality, methods of extraction, and data reliability are hurdles to utilization of archival samples. We compared three different platforms for performing RNA-seq using archival FFPE oropharyngeal squamous carcinoma (OPSCC) specimens stored up to 20 years, as part of an investigation of transcriptional profiles related to health …

Relationships Of Personality Traits With The Taxonomic Composition Of The Gut Microbiome Among Psychiatric Inpatients, William Orme, Sandra L Grimm, Divya S N Vella, J Christopher Fowler, B Christopher Frueh, Benjamin L Weinstein, Joseph Petrosino, Cristian Coarfa, Alok Madan

Faculty, Staff and Students Publications

Objective: Through the brain-gut-microbiome axis, myriad psychological functions that affect behavior share a dynamic, bidirectional relationship with the intestinal microbiome. Little is known about the relationship between personality-a stable construct that influences social- and health-related behaviors-and the bacterial ecosystem. The authors of this exploratory study examined the relationship between general and maladaptive personality traits and the composition of the gut microbiome.

Methods: In total, 105 psychiatric inpatients provided clinical data and fecal samples. Personality traits were measured with the five-factor model of personality, the Structured Clinical Interview for DSM-IV Axis II Personality Disorders, and the Personality Inventory for DSM-5; 16S …

Nf-Κb-Mediated Oxidative Stress Drives Cigarette Smoke-Induced Emt In Human Bronchial Cells, Sarah M. Alqithami

Theses and Dissertations--Toxicology and Cancer Biology

Cigarette smoke contains over 7,000 chemicals, many being carcinogens and proinflammatory agents contributing to chronic respiratory diseases like COPD and lung cancer. This study investigated responses of human bronchial epithelial cells (HBECs) to cigarette smoke condensate (CSC), focusing on oxidative stress and NF-κB signaling. Three HBEC lines were exposed to non-cytotoxic CSC doses for 48 hours, inducing morphological changes consistent with epithelial-to-mesenchymal transition (EMT). RNA sequencing revealed transcriptomic shifts in all cell lines, particularly affecting genes related to oxidative stress, inflammation, hypoxia, and metabolism. Enrichment analyses confirmed activation of NRF2 antioxidant, NF-κB and IL-17 inflammatory, and hypoxiainducible factor pathways, indicating …

The Effect Of Hypochlorous Acid On Cultured Osteoblast And Escherichia Coli, Cristina Flaquer Fusté

Graduate Theses/Dissertations

Hypochlorous acid (HOCl), a naturally occurring compound in neutrophils, has been used as an antimicrobial in wound treatment. Osteoblasts, bone-forming cells, within the bone tissue play a large role in bone fracture healing. Orthopedic infections are challenging to treat and highly morbid, including surgical site infection of arthroplasty procedures or infection in the setting of compound fractures. HOCl is being considered as a surgical antiseptic to decrease infections in orthopedic surgical procedures. This study therefore seeks to determine the effects of HOCl on osteoblasts and E. coli. Cultured osteoblasts were incubated with varying concentrations of HOCl to examine osteoblast …

Characterization Of The Overexpression Of Reca Homologs Rad51 And Dmc1 In Tetrahymena Thermophila, Jianna M. Cox

Graduate Theses/Dissertations

RecA homologs, Dmc1 and Rad51, work to repair DNA double-strand breaks (DSBs) within the cell through the recombination of homologous sections of DNA. Dmc1 works to repair programmed DSBs through meiotic recombination, while Rad51 functions to repair both meiotic and non-meiotic DSBs, the latter repaired through the process of homologous recombination repair (HHR). Chemotherapeutics, exogenous agents, work to form DSBs in cancer cells, attempting to inhibit the cell’s growth. A hyper recombinant phenotype is often seen in cancer cells due to the overexpression of RAD51, leading to drug resistance, the persistence of cancers, and an overall poor patient outcome. …

Age-Related Variations In Hba1c Improvemecnts: Insights From A Telehealth-Supported Community-Based Intervention, Laura Porterfield, Xiaoying Yu, Amber B Amspoker, Craig A Johnston, Aanand D Naik, Salim S Virani, Christie M Ballantyne, Ashok Balasubramanyam, Elizabeth M Vaughan

Faculty, Staff and Students Publications

Background and objectives: We previously demonstrated that a telehealth-supported community health worker (CHW) intervention significantly improved clinical outcomes in diabetes care. However, the extent to which these benefits vary across different age groups remains unclear. This study evaluated the effectiveness of a CHW-led multidimensional diabetes intervention in reducing HbA1c across age groups.

Research design and methods: We conducted a retrospective analysis of 10 studies (n = 301) that focused on low-income Hispanic adults with or at risk for type 2 diabetes. The intervention included CHW-participant coaching via mobile Health (mHealth), monthly CHW-led group education, and bidirectional mHealth feedback among …

Pathology Discovered In The “First Patient” Can Be The Silent Teacher Of Self-Directed Learning, Mary Leupold, Daniel Topping, R. John Cork, Robin Mcgoey, Guenevere Rae

School of Medicine Faculty Publications

Pathology found during cadaveric dissection has been used to model integrative teaching methods for medical students at several institutions. Recent evidence has shown that pathology found during dissection can be used in the design of self-directed learning (SDL) activities with standards that are difficult to meet. This study presents a novel method for providing formative feedback, one of the most challenging aspects for LCME accreditation of SDL activities. Three practitioners (two board certified pathologists and one board certified family physician) reviewed and rated pathological findings during routine dissection by first year medical students in the gross anatomy laboratory in New …

Decoding Ras Mutations In Thyroid Cancer: A Meta-Analysis Unveils Specific Links To Distant Metastasis And Increased Mortality, Isabel Riccio, Alexandra Laforteza, Madeleine B. Landau, Mohammad H. Hussein, Joshua Linhuber, Jonathan Staav, Peter P. Issa, Eman A. Toraih, Emad Kandil

School of Medicine Faculty Publications

Background/objectives: RAS mutations are common in thyroid cancer, but their impact on clinical outcomes remains controversial. This study aimed to evaluate the prevalence of RAS mutations in thyroid cancer and their association with various clinical and pathological features. Methods: We conducted a systematic review and meta-analysis of studies reporting on RAS mutations in thyroid cancer. Both one-arm and pairwise meta-analyses were performed to compare outcomes between RAS-mutated (RAS+) and wild-type (RAS-) thyroid cancers. Results: Our analysis included 2552 thyroid cancer patients from 17 studies. The overall prevalence of RAS mutations was 35.4 % (95 % CI: 22.7 %–50.7 %). NRAS …

Large-Scale Crispr/Cas9 Deletions Within The Wfdc Gene Cluster Uncover Gene Functionality And Critical Roles In Mammalian Reproduction, Katarzyna Kent, Kaori Nozawa, Rachel Parkes, Laura Dean, Frey Daniel, Mei Leng, Antrix Jain, Anna Malovannaya, Martin M Matzuk, Thomas X Garcia

Faculty, Staff and Students Publications

Despite 96 million years of evolution separating humans and rodents, 11 closely related reproductive tract-specific genes in humans—SPINT3, WFDC6, EPPIN, WFDC8, WFDC9, WFDC10A, WFDC11, WFDC10B, WFDC13, SPINT4, and WFDC3—and the 13 reproductive tract-specific orthologous genes in mice, form highly conserved syntenic gene clusters indicative of conserved, combined critical functions. Further, despite significant progress toward a nonhormonal male contraceptive targeting the protein encoded by one of these genes, epididymal peptidase inhibitor (EPPIN), and associations found between mutations in EPPIN and an increased risk of male infertility, neither EPPIN nor …

Uba1 Inhibition Sensitizes Cancer Cells To Parp Inhibitors, Sharad Awasthi, Lacey E Dobrolecki, Christina Sallas, Xudong Zhang, Yang Li, Sima Khazaei, Sumanta Ghosh, Collene R Jeter, Jinsong Liu, Gordon B Mills, Shannon N Westin, Michael T Lewis, Weiyi Peng, Anil K Sood, Timothy A Yap, S Stephen Yi, Daniel J Mcgrail, Nidhi Sahni

Faculty, Staff and Students Publications

Therapeutic strategies targeting the DNA damage response, such as poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi), have revolutionized cancer treatment in tumors deficient in homologous recombination (HR). However, overcoming innate and acquired resistance to PARPi remains a significant challenge. Here, we employ a genome-wide CRISPR knockout screen and discover that the depletion of ubiquitin-activating enzyme E1 (UBA1) enhances sensitivity to PARPi in HR-proficient ovarian cancer cells. We show that silencing or pharmacological inhibition of UBA1 sensitizes multiple cell lines and organoid models to PARPi. Mechanistic studies uncover that UBA1 inhibition not only impedes HR repair to sensitize cells to PARP inhibition …

Development Of A Ripk1 Degrader To Enhance Antitumor Immunity, Xin Yu, Dong Lu, Xiaoli Qi, Rishi Ram Paudel, Hanfeng Lin, Bryan L Holloman, Feng Jin, Longyong Xu, Lang Ding, Weiyi Peng, Meng C Wang, Xi Chen, Jin Wang

Faculty, Staff and Students Publications

The scaffolding function of receptor interacting protein kinase 1 (RIPK1) confers intrinsic and extrinsic resistance to immune checkpoint blockades (ICBs) and emerges as a promising target for improving cancer immunotherapies. To address the challenge posed by a poorly defined binding pocket within the intermediate domain of RIPK1, here we harness proteolysis targeting chimera (PROTAC) technology to develop a RIPK1 degrader, LD4172. LD4172 exhibits potent and selective RIPK1 degradation both in vitro and in vivo. Degradation of RIPK1 by LD4172 triggers immunogenic cell death, enhances tumor-infiltrating lymphocyte responses, and sensitizes tumors to anti-PD1 therapy in female C57BL/6J mice. This work reports …