Digital Commons Network^™

Understanding The Mechanism Of Genomic Instability During Replicative Aging In Budding Yeast, Sangita Pal

Dissertations and Theses (Open Access)

Aging brings a gradual decline in molecular fidelity and biological functionality, resulting in age related phenotypes and diseases. Despite continued efforts to uncover the conserved aging pathways among eukaryotes, exact molecular causes of aging are still poorly understood. One of the most important hallmarks of aging is increased genomic instability. However, there remains much ambiguity as to the cause. I am studying the replicative life span (RLS) of the genetically tractable model organism Saccharomyces cerevisiae, or budding yeast using the innovative “mother enrichment program” as the method to isolate unparalleled numbers of aged yeast cells to investigate the molecular changes …

Targeting Autophagy To Improve Efficacy Of Cdk4/6 Inhibition In Breast Cancer, Smruthi Vijayaraghavan

Dissertations and Theses (Open Access)

Deregulation of the cell cycle machinery is a hallmark of cancer, leading to aberrant proliferation and tumorigenesis. The crucial role of the CDK4/6-Cyclin D pathway has led to the development and FDA approval (palbociclib, ribociclib) of CDK4/6 inhibitors for the treatment of advanced estrogen receptor positive breast cancer. However, three major clinical challenges remain: i) adverse events leading to discontinuation of therapy and ii) lack of reliable biomarkers to identify responsive patients and iii) acquired resistance to CDK4/6 inhibitors. Previous in vitro studies have shown that palbociclib mediated CDK4/6 inhibition induces G1 arrest and senescence in ER+ breast cancer cells, …

Stromal Fibroblasts Restrain The Rate Of Colon Cancer Progression And Metastasis By Suppressing Regulatory T Cells And Colon Cancer Stem Cells, Changsoo Kwak

Dissertations and Theses (Open Access)

The initiation, progression, and metastasis of tumors involve not only cancer cells, but also the tumor microenvironment, which consists of immune or inflammatory cells, fibroblasts, endothelial cells, and extracellular matrix components (ECM). Fibroblasts are ubiquitous stromal cells that can influence other neighboring cell types through the secretion of chemokines, cytokines, ECM, ECM remodeling enzymes, and other metabolites. Myofibroblasts are a distinct subtype of fibroblasts characterized by expression α-smooth muscle actin (αSMA). These cells are a dominant component of the microenvironment, and a FSP1 and FAP could be a different clone of fibroblasts. Myofibroblasts also have been known to contribute to …

Ms171: Interview With Diana Chow, Diana Shu-Lian Chow Ph.D., Houston Academy Of Medicine-Texas Medical Center Library

Texas Medical Center - Women's History Project

Diana Shu-Lian Chow, Ph.D., is an outstanding researcher at the University of Houston College of Pharmacy, where she began her career in 1981. She has authored or co-authored more than 50 peer-reviewed journal articles, three book chapters and more than 200 abstracts presented at national and international scientific conference or meetings. She is the editor of the British Journal of Pharmacology, editorial board member for the Journal of Drug Development and Industrial Pharmacy and a reviewer for more than a dozen journals.

She holds more than 10 U.S. and international patents, and in 2009, the Houston Intellectual Property Law Association …

Ms171: Interview With Kathryn Peek, Kathryn Elaine Peek Ph.D., Houston Academy Of Medicine-Texas Medical Center Library

Texas Medical Center - Women's History Project

An oral history interview with Kathryn Elaine Hickman Peek about her career as a biomedical administrator and educator at many institutions in the Texas Medical Center.

Kathryn Elaine Peek, Ph.D. completed her bachelor’s degree in English and embarked on a first career as a public school teacher. She obtained master’s degrees in biology and behavioral sciences at the University of Houston and UH Clear Lake during two stays in the Houston area. She entered the University of Texas Graduate School of Biomedical Sciences at what is now the McGovern Medical School at the age of 39. She graduated with a …

Ms171: Interview With Millicent Goldschmidt, Millicent Goldscmidt Ph.D., Houston Academy Of Medicine-Texas Medical Center Library

Texas Medical Center - Women's History Project

An oral history interview with Millicent Goldschmidt about her career at University of Texas Health Science Center at Houston (UTHealth) where she has held faculty positions in the Department of Diagnostic and Biomedical Sciences at UTHealth School of Dentistry, UTHealth Medical School, and the Graduate School of Biomedical Sciences.

Millicent Edna Goldschmidt, Ph.D., came to the Texas Medical Center after an educational journey that included parental objections and a husband’s ethical concerns about research.

Once in Houston, her professional journey took her to almost every institution in the Texas Medical Center – from Baylor College of Medicine to The University …

Ms 104 James H. Steele, Dvm, Ph Papers (1938-­2010), James H. Steele

Manuscript Finding Aids

The James H. Steele DVM, MPH papers document the life and career of James H. Steele, who is considered the father of veterinary public health. These papers provide information about Steele's research, professional activities and correspondence, travels, and achievements. See more at MS 104.

Caring Minds, Uthealth Cizik School Of Nursing

Caring Minds

No abstract provided.

Targeting Apoptotic Pathways To Overcome Drug Resistance In Acute Myeloid Leukemia, Rongqing Pan

Dissertations and Theses (Open Access)

Evasion of apoptosis is integral to tumorigenesis and drug resistance. BCL-2 and p53 proteins represent two focal nodes in convergent apoptosis signaling. Upregulation of anti-apoptotic BCL-2 family members and inactivation of p53 functions are two canonical approaches exploited by cancer cells to escape apoptosis. In the current study, we find that BCL-2 protein is highly expressed in acute myeloid leukemia (AML) cells. BCL-2–specific inhibitor ABT-199 potently induces mitochondrial apoptosis in AML cells and effectively kills AML stem/progenitor cells. Our biomarker studies demonstrate that both BH3 profiling and the expression profiling of BCL-2 proteins may serve as predictive biomarkers for the …

Regulation Of Hnrnpa1 By Micrornas Controls The Mir-18a–K-Ras Axis In Chemotherapy-Resistant Ovarian Cancer, Cristian Rodriguez-Aguayo, Paloma Del C Monroig, Roxana S Redis, Emine Bayraktar, Maria I Almeida, Cristina Ivan, Enrique Fuentes-Mattei, Mohammed H Rashed, Arturo Chavez-Reyes, Bulent Ozpolat, Rahul Mitra, Anil K Sood, George A Calin, Gabriel Lopez-Berestein

Faculty, Staff and Student Publications

The regulation of microRNA (miRNA) biogenesis, function and degradation involves a range of mechanisms, including interactions with RNA-binding proteins. The potential contribution of regulatory miRNAs to the expression of these RNA interactor proteins that could control other miRNAs expression is still unclear. Here we demonstrate a regulatory circuit involving oncogenic and tumor-suppressor miRNAs and an RNA-binding protein in a chemotherapy-resistant ovarian cancer model. We identified and characterized miR-15a-5p and miR-25-3p as negative regulators of hnRNPA1 expression, which is required for the processing of miR-18a-3p, an inhibitor of the

The Neurobiological Mechanisms Of Generalized Anxiety Disorder And Chronic Stress, Michelle A Patriquin, Sanjay J Mathew

Staff and Researcher Publications

Two classification systems are now at the forefront of clinical psychiatric research: (1) Diagnostic and Statistical Manual, Fifth Edition and (2) the National Institutes of Mental Health Research Domain Criteria. Herein, we propose that these two classification systems are complementary rather than mutually exclusive, and when combined provide important information for understanding aspects of the pathophysiology related to Generalized Anxiety Disorder (GAD). The neurobiological literature for GAD and one relevant research domain criteria component, sustained threat, are reviewed from multiple units of analysis (genetic, neuroimaging, neuroendocrine, and psychophysiological). It is hypothesized that generating a comprehensive, biologically based understanding of the …

Ms 019 Guide To Matilda Benyesh-Melnick, Md Papers (1956-1974), Matilda Benyesh-Melnick (1926-2020)

Manuscript Finding Aids

The Matilda Benyesh-Melnick, MD papers contain research journals, reprints, magazines, reports, symposia and an undated manuscript related to her career in virology. Materials focus on the research that she conducted and collected between 1956 and 1974. See more at MS 019.

The Role Of Two Homologous E3 Ligases In Muscle Physiology, Gabrielle F. Gloston

Dissertations and Theses (Open Access)

Ubiquitin-mediated proteasomal degradation is an essential cellular function that is coordinated by three key components: E1 ubiquitin activating enzyme, E2 ubiquitin conjugating enzyme, and E3 ubiquitin ligases. There are an estimated 600 E3 ligases, some of which share high sequence homology; however, the functional significance often remains unknown. FBXL3 and FBXL21 are two homologous E3 ligases that have previously been reported to dictate circadian periodicity, with FBXL3 being the dominant E3 ligase and FBXL21 playing a regulatory role. A recent Yeast Two-Hybrid screen revealed a new shared target of FBXL3 and FBXL21: Telethonin (also known as TCAP). TCAP is a …

Using Mouse Models To Define How The P53 R72p Polymorphism Impacts The Adverse Effects Of Doxorubicin And Ionizing Radiation, Emily Dominguez

Dissertations and Theses (Open Access)

The single nucleotide polymorphism (SNP) at codon 72 of the tumor suppressor gene p53 codes for either an arginine (R) or proline (P) (p53 R72P). This SNP may impact how cells respond to genotoxic insult. Studies in cell culture and in tissues from mouse models of the SNP indicate that, in response to gentoxic treatment, the two variants may differentially induce apoptosis and expression of p53 target genes. In epidemiological studies, the P variant is associated with decreased cancer survival and increased risk of side-effects from genotoxic cancer treatment. Genotoxic therapy is still the mainstay of cancer treatment, and doxorubicin …

The Role Of Streptococcus Gallolyticus Subspecies Gallolyticus In Colon Cancer Development, Jennifer L. Herold

Dissertations and Theses (Open Access)

Colorectal cancer (CRC) is the third most common cancer in men and women and is also the third most common cause of cancer death. A large body of evidence points towards the possibility that bacteria can have a significant impact on the development of cancer. It has been suggested that Streptococcus gallolyticus subsp. gallolyticus, a group D streptococci, may play a role in the development of CRC. Sg, formerly S. bovis biotype I, has been shown to be highly associated with CRC. In observing patients with either Sg bacteremia or endocarditis it was found that 25-80% of …

Maguk Scaffolds Organize A Key Synaptic Complex In Horizontal Cell Processes Contacting Photoreceptors, Alejandro Vila, Ph.D.

Dissertations and Theses (Open Access)

Synaptic processes and plasticity of synapses are mediated by large suites of proteins. In most cases, many of these proteins are tethered together by synaptic scaffold proteins. Scaffold proteins have a large number and typically a variety of protein interaction domains that allow many different proteins to be assembled into functional complexes. As each scaffold protein has a different set of protein interaction domains and a unique set of interacting partners, the presence of synaptic scaffolds can provide insight into the molecular mechanisms that regulate synaptic processes. In studies of rabbit retina, we found SAP102 and Chapsyn110 selectively localized in …

Characterization Of Vesicular Monoamine Transporter 2 And Its Role In Parkinson's Disease Pathogenesis Using Drosophila, Antonio Joel Tito Jr., Sheng Zhang

Dissertations and Theses (Open Access)

Parkinson’s disease (PD) is a progressive neurodegenerative disorder caused by the selective loss of the dopaminergic neurons in the Substantia nigra pars compacta region of the brain. PD is also the most common neurodegenerative disorder and the second most common movement disorder. PD patients exhibit the cardinal symptoms, including tremor of the extremities, rigidity, slowness of movement, and postural instability, after 70-80% of DA neurons degenerate. It is, therefore, imperative to elucidate the underlying mechanisms involved in the selective degeneration of DA neurons. Although increasing numbers of PD genes have been identified, why these largely widely expressed genes induce …

Targeting Pd-1/Pdl-1 Signaling In The Treatment Of Osteosarcoma Lung Metastasis, Pooja Dhupkar 3012359

Dissertations and Theses (Open Access)

Osteosarcoma (OS) manifests itself as pulmonary metastasis, which is a major cause of death in OS patients. Novel treatments like immunotherapy hold promise for the treatment of OS pulmonary metastasis. However, immunosuppressive mechanisms such as binding of immune inhibitory receptor, PD-1 with PDL-1, which is upregulated in cancer cells, may cause disease relapse.

The effect of PD-1 blockade on NK cells and macrophages has not been investigated till date. The aim of this study was to determine if PD-1 blockade leads to of OS lung metastasis regression and study the role of NK cells and/or macrophages in the anti-PD-1 responses. …

Organ Specific Vascular Response To Fibrosis Affects Breast Cancer Metastatic Organotropism, Eliot S. Fletcher, Eliot S. Fletcher

Dissertations and Theses (Open Access)

The solid tumor microenvironment, pre-metastatic niche, and fibrotic environment are known to have significant biochemical and biomechanical similarities to the fibrotic environment. All have significantly increased levels of factors such as TGFβ, HIF1α, TNFα, PDGF, VEGF, FGF, interleukins and other growth factors that are known to be pro-tumorigenic. Clinical and basic science research has shown that fibrosis presents an environment that favors tumor growth, such as hepatocellular carcinoma being commonly preceded by liver cirrhosis, or bleomycin induced lung fibrosis enhancing pulmonary metastasis in mouse models of breast cancer. In addition to the evidence indicating that fibrosis enhances primary tumor growth …

Cellular And Genetic Bases Of Cold Nociception And Nociceptive Sensitization In Drosophila Larvae, Heather N. Turner

Dissertations and Theses (Open Access)

Organisms from flies to mammals utilize thermoreceptors to detect and respond to noxious thermal stimuli. Although much is understood about noxious heat avoidance, our understanding of the basic biology of noxious cold perception is gravely minimal. Numerous clinical conditions disrupt the sensory machinery, such as in patients suffering from tissue damage (from wound or sunburn), or injury to the peripheral nerves, as in patients with diabetes or undergoing chemotherapy. Our goal is to determine the genetic basis for noxious cold perception and injury-induced nociceptive sensitization using the genetically tractable Drosophila model. Using a novel "cold probe" tool and assay we …

Novel Simulation To Avoid Bias In Measurement Of Hyperpolarized Pyruvate: Demonstrated In Phantom And In Vivo, Christopher M. Walker

Dissertations and Theses (Open Access)

Dynamic nuclear polarization creates a transient hyperpolarized nuclear state that can dramatically increase the signal detected by magnetic resonance imaging. This signal increase allows real-time spectroscopic imaging of specific metabolites in vivo by magnetic resonance. Real-time imaging of both the spatial and chemical fate of hyperpolarized metabolites is showing great promise to meaningfully benefit clinical care of cancer patients. Imaging of hyperpolarized agents will have a larger clinical impact if it can function as a quantitative modality upon which clinical decisions can be made. However, quantitative measurement of hyperpolarized agents is currently difficult due to the restrictions imposed by the …

Comparative Efficacy Of Nebivolol And Metoprolol To Prevent Tachycardia-Induced Cardiomyopathy In A Porcine Model, Alireza Nazeri, Macarthur A Elayda, Ana Maria Segura, Raymond F Stainback, Joanna Nathan, Vei-Vei Lee, Christina Bove, Luiz Sampaio, Brian Grace, Ali Massumi, Mehdi Razavi

The Texas Heart Institute Journal

Chronic tachycardia is a well-known cause of nonischemic cardiomyopathy. We hypothesized that nebivolol, a β-blocker with nitric oxide activity, would be superior to a pure β-blocker in preventing tachycardia-induced cardiomyopathy in a porcine model.

Fifteen healthy Yucatan pigs were randomly assigned to receive nebivolol, metoprolol, or placebo once a day. All pigs underwent dual-chamber pacemaker implantation. The medication was started the day after the pacemaker implantation. On day 7 after implantation, each pacemaker was set at atrioventricular pace (rate, 170 beats/min), and the pigs were observed for another 7 weeks. Transthoracic echocardiograms, serum catecholamine levels, and blood chemistry data were …

Ms 020 Guide To Leon Dmochowski, Md, Phd Papers (1947-1977), Leon Dmochowski (1909-1981)

Manuscript Finding Aids

The Leon Dmochowski, MD, PhD papers contain article reprints, reports and an undated manuscript related to his career in oncology and virology. The collection contains 2 boxes equaling 1 cubic foot, the materials are mostly in good condition. One item has water damage. See more at MS 020.

Role Of Phosphorylation In The Regulation Of Prmt5, Alexsandra B. Espejo

Dissertations and Theses (Open Access)

PRMT5 is a member of a group of proteins that mediate arginine methylation. It is involved in diverse cellular processes, including cell differentiation, splicing, transcription elongation and epigenetic silencing, and its expression is dysregulated in many cancers. Due to its pleiotropic functions, PRMT5 is subject to multi-level regulation. Post-translational modification (PTM) of proteins can modulate an array of cellular processes by regulating both protein interactions and protein structural changes. PRMT5 is commonly found associated with other proteins; these interactions seem to control both its catalytic activity and its substrate specificity. Recently, it became clear that PRMT5 is phosphorylated at a …

Mechanistic And Functional Characterization Of B And T Lymphocyte Attenuator (Btla) In Cd8 Tumor Infiltrating Lymphocytes, Krit Ritthipichai

Dissertations and Theses (Open Access)

This dissertation project focused on understanding the functional role of BTLA on CD8⁺ Tumor Infiltrating Lymphocytes (TIL) from metastatic melanoma patients. Clinical trials of adoptive T-cell therapy (ACT) using autologous ex vivo expanded TIL have demonstrated the great potential of this immunotherapy with an overall clinical response rate 40-50% for stage IV metastatic melanoma patients. We have investigated a number of biomarkers in both the infused TIL and the tumor microenvironment for their association with clinical response. Surprisingly, a subset of CD8⁺ TIL expressing the co-inhibitory molecule BTLA (B-and-T lymphocyte attenuator) was highly associated with clinical response, while …

Regulation Of Breast Cancer Initiation And Progression By 14-3-3zeta, Chia-Chi Chang

Dissertations and Theses (Open Access)

14-3-3ζ is a ubiquitously expressed family member of proteins that have been implicated to have oncogenic potential through its interactions and involvement in cancer initiation and progression. 14-3-3ζ belongs to the highly conserved 14-3-3ζ protein family and modulates numerous pathways in cancer. Overexpression of 14-3-3ζ is an early event, occurs in more than 40% of human breast cancer cases, and is associated with disease recurrence and poor prognosis. Metabolic reprogramming is a hallmark of cancer. Cancer cells elevate aerobic glycolysis to produce metabolic intermediates and reducing equivalents, thereby facilitating cellular adaptation to the adverse environment and sustaining fast proliferation. Interestingly, …

The Impact Of Cortical State On Neural Coding And Behavior, Charles Beaman

Dissertations and Theses (Open Access)

The brain is never truly silent – up to 80% of its energy budget is expended during ongoing activity in the absence of sensory input. Previous research has shown that sensory neurons are not exclusively influenced by external stimuli but rather reflect interactions between sensory inputs and the ongoing activity of the brain. Yet, whether fluctuations in the state of cortical networks influence sensory coding in neural circuits and the behavior of the animal are unknown. To shed light on this issue, we conducted multi-unit electrophysiology experiments in visual areas V1 and V4 of behaving monkeys. First, we studied the …

Clinical Significance Of Homologous Recombination Deficiency Score Testing In Endometrial Cancer, Jean M. Hansen

Dissertations and Theses (Open Access)

Objectives: Homologous recombination deficiency (HRD) score is related to chemotherapy response in breast and ovarian cancers. The role of HRD is unknown in endometrial cancer. We examined the relationship between HRD score and survival in a cohort of endometrial cancer patients and with tumor growth using murine orthotopic models.

Methods: TCGA was queried to determine frequency and clinical significance of alterations in the HR pathway in endometrial cancer. 137 formalin-fixed paraffin-embedded endometrioid adenocarcinoma patient samples were tested for HRD score, microsatellite instability (MSI) and high mutation load (HML) using a next generation sequencing assay targeting the coding regions of 43 …

Development Of Rational Combination Therapy With Parp Inhibitors And Kinase Inhibitors In Tnbc, Wen-Hsuan Yu

Dissertations and Theses (Open Access)

Poly (ADP-ribose) polymerase inhibitors (PARPi) emerge as potential targeting drugs for BRCA-deficient cancers including triple negative breast cancer (TNBC). However, it has been reported that a subgroup of patients even with BRCA mutation fails to respond to PARPi in multiple clinical trials. In this study, we identified c-Met, a tyrosine kinase, phosphorylates PARP1 at Y907 and that the phosphorylation increases PARP1 activity, thereby rendering cancer cells resistant to PARPi. The combination of c-Met inhibitors (METi) and PARPi has a synergistic effect for c-Met overexpressed TNBC in vitro and in vivo. In addition to c-Met, through functional analysis, we found …

Interrogating Dux4 Mrna 3′ End Processing, Natoya J. Peart

Dissertations and Theses (Open Access)

Double Homeobox 4, Dux4, is the leading candidate gene for Facioscapulohumeral Dystrophy (FSHD). FSHD is the third most common muscular dystrophy, and is characterized by progressive muscle weakness primarily in the upper body. In individuals diagnosed with FSHD, Dux4 is inappropriately expressed in somatic cells due to two conditions. The first is hypomethylation of the subtelomeric D4Z4 repeats on chromosome 4. Each D4Z4 repeat on chromosome 4 is 3.3kb in length and contains the open reading frame for Dux4. Hypomethylation of the D4Z4 repeats primarily occurs due to contraction of the repeats from 11-100 (typical numbers in the healthy population) …