publisher:("Texas Medical Center")

Texas Medical Center

1. Tonthat, Nam K. Molecular mechanism by which the Escherichia coli nucleoid occlusion factor, SlmA, keeps cytokinesis in check.

Degree: PhD, 2011, Texas Medical Center

URL: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/107

► Cell division or cytokinesis is one of the most fundamental processes in biology and is essential for the propagation of all living species. In Escherichia… (more)

▼ Cell division or cytokinesis is one of the most fundamental processes in biology and is essential for the propagation of all living species. In Escherichia coli, cell division occurs by ingrowth of the membrane envelope at the cell center and is orchestrated by the FtsZ protein. FtsZ self-assembles into linear protofilaments in a GTP dependent manner to form a cytoskeletal scaffold called the Z-ring. The Z-ring provides the framework for the assembly of the division apparatus and determines the site of cytokinesis. The total amount of FtsZ molecules in a cell significantly exceeds the concentration required for Z-ring formation. Hence, Z-ring formation must be highly regulated, both temporally and spatially. In particular, the assembly of Z-rings at the cell poles and over chromosomal DNA must be prevented. These inhibitory roles are played by two key regulatory systems called the Min and nucleoid occlusion (NO) systems. In E. coli, Min proteins oscillate from pole to pole; the net result of this oscillatory process is the formation of a zone of FtsZ inhibition at the cell poles. However, the replicated nucleoid DNA near the midcell must also be protected from bisection by the Z-ring which is ensured by NO. A protein called SlmA was shown to be the effector of NO in E. coli. SlmA was identified in a screen designed to isolate mutations that were lethal in the absence of Min, hence the name SlmA (synthetic lethal with a defective Min system). Furthers SlmA was shown to bind DNA and localize to the nucleoid fraction of the cell. Additionally, light scattering experiments suggested that SlmA interacts with FtsZ-GTP and alters its polymerization properties. Here we describe studies that reveal the molecular mechanism by which SlmA mediates NO in E. coli. Specifically, we determined the crystal structure of SlmA, identified its DNA binding site specificity, and mapped its binding sites on the E. coli chromosome by chromatin immuno-precipitation experiments. We went on to determine the SlmA-FtsZ structure by small angle X-ray scattering and examined the effect of SlmA-DNA on FtsZ polymerization by electron microscopy. Our combined data show how SlmA is able to disrupt Z-ring formation through its interaction with FtsZ in a specific temporal and spatial manner and hence prevent nucleoid guillotining during cell division. Advisors/Committee Members: Maria A. Schumacher, Richard G. Brennan, John E. Ladbury.

Subjects/Keywords: bacterial cell division; chromosome segregation; FtsZ Z-ring formation; nucleoid occlusion; SlmA; Biochemistry, Biophysics, and Structural Biology

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Tonthat, N. K. (2011). Molecular mechanism by which the Escherichia coli nucleoid occlusion factor, SlmA, keeps cytokinesis in check. (Doctoral Dissertation). Texas Medical Center. Retrieved from https://digitalcommons.library.tmc.edu/utgsbs_dissertations/107

Chicago Manual of Style (16^th Edition):

Tonthat, Nam K. “Molecular mechanism by which the Escherichia coli nucleoid occlusion factor, SlmA, keeps cytokinesis in check.” 2011. Doctoral Dissertation, Texas Medical Center. Accessed February 26, 2021. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/107.

MLA Handbook (7^th Edition):

Tonthat, Nam K. “Molecular mechanism by which the Escherichia coli nucleoid occlusion factor, SlmA, keeps cytokinesis in check.” 2011. Web. 26 Feb 2021.

Vancouver:

Tonthat NK. Molecular mechanism by which the Escherichia coli nucleoid occlusion factor, SlmA, keeps cytokinesis in check. [Internet] [Doctoral dissertation]. Texas Medical Center; 2011. [cited 2021 Feb 26]. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/107.

Council of Science Editors:

Tonthat NK. Molecular mechanism by which the Escherichia coli nucleoid occlusion factor, SlmA, keeps cytokinesis in check. [Doctoral Dissertation]. Texas Medical Center; 2011. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/107

Texas Medical Center

2. Jung, Youngsin. Analysis of Band 4.1B in Integrin-Mediated Cell Adhesion and Signaling.

Degree: PhD, 2011, Texas Medical Center

URL: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/108

► Band 4.1B is a cytoskeletal adaptor protein that regulates various cellular behavior; however, the mechanisms by which Band 4.1B contributes to intracellular signaling are… (more)

▼ Band 4.1B is a cytoskeletal adaptor protein that regulates various cellular behavior; however, the mechanisms by which Band 4.1B contributes to intracellular signaling are unclear. This project addresses in vivo and in vitro functions for Band 4.1B in integrin-mediated cell adhesion and signaling. Band 4.1B has been shown to bind to β8 integrin, although cooperative functions of these two proteins have not been determined. Here, functional links between β8 integrin and Band 4.1B were investigated using gene knockout strategies. Ablation of β8 integrin and Band 4.1B genes resulted in impaired cardiac morphogenesis, leading to embryonic lethality by E11.5. These embryos displayed malformation of the outflow tract that was likely linked to abnormal regulation of cardiac neural crest migration. These data indicate the importance of cooperative signaling between β8 integrin and Band 4.1B in cardiac development. The involvement of Band 4.1B in integrin-mediated cell adhesion and signaling was further demonstrated by studying its functional roles in vitro. Band 4.1B is highly expressed in the brain, but its signaling in astrocytes is not understood. Here, Band 4.1B was shown to promote cell spreading likely by interacting with β1 integrin via its band 4.1, ezrin, radixin, and moesin (FERM) domain in cell adhesions. In astrocytes, both Band 4.1B and β1 integrin were expressed in cell-ECM contact sites during early cell spreading. Exogenous expression of Band 4.1B, especially its FERM domain, enhanced cell spreading on fibronectin, an ECM ligand for β1 integrin. However, the increased cell spreading was prohibited by blocking β1 integrin. These findings suggest that Band 4.1B is crucial for early adhesion assembly and/or signaling that are mediated by β1 integrin. Collectively, this study was the first to establish Band 4.1B as a modulator of integrin-mediated adhesion and signaling. Advisors/Committee Members: Joseph H. McCarty, Ph.D., Gary E. Gallick, Ph.D., Georg Halder, Ph.D..

Subjects/Keywords: Band 4.1B; Integrins; Development; Cell adhesion; Cell migration; Cell Biology; Developmental Biology

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Jung, Y. (2011). Analysis of Band 4.1B in Integrin-Mediated Cell Adhesion and Signaling. (Doctoral Dissertation). Texas Medical Center. Retrieved from https://digitalcommons.library.tmc.edu/utgsbs_dissertations/108

Chicago Manual of Style (16^th Edition):

Jung, Youngsin. “Analysis of Band 4.1B in Integrin-Mediated Cell Adhesion and Signaling.” 2011. Doctoral Dissertation, Texas Medical Center. Accessed February 26, 2021. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/108.

MLA Handbook (7^th Edition):

Jung, Youngsin. “Analysis of Band 4.1B in Integrin-Mediated Cell Adhesion and Signaling.” 2011. Web. 26 Feb 2021.

Vancouver:

Jung Y. Analysis of Band 4.1B in Integrin-Mediated Cell Adhesion and Signaling. [Internet] [Doctoral dissertation]. Texas Medical Center; 2011. [cited 2021 Feb 26]. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/108.

Council of Science Editors:

Jung Y. Analysis of Band 4.1B in Integrin-Mediated Cell Adhesion and Signaling. [Doctoral Dissertation]. Texas Medical Center; 2011. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/108

Texas Medical Center

3. Maili, Lorena. COCAINE DEPENDENCE: THE ROLE OF SEROTONIN GENES IN.

Degree: MS, 2011, Texas Medical Center

URL: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/109

► Animal studies have shown that behavioral responses to cocaine-related cues are altered by serotonergic medications. The effects of pharmacological agents on serotonin receptors 2a… (more)

▼ Animal studies have shown that behavioral responses to cocaine-related cues are altered by serotonergic medications. The effects of pharmacological agents on serotonin receptors 2a (5-HT2A) and 2c (5-HT2C), have yielded results suggesting that selective 5-HT2A antagonists and 5-HT2C agonists promote the disruption of cocaine-associated memories. One measure of cocaine related cues in humans is attentional bias, in which cocaine dependent individuals show greater response latency for cocaine related words than neutral words. Data from our laboratory shows that cocaine dependent subjects have altered attentional bias compared to controls. The purpose of this thesis was to investigate the role of the serotonin system in attentional bias and impulsivity in cocaine dependent individuals. We focused on the serotonin transporter, serotonin receptors 2A and 2C and tryptophan hydroxylase 1 and 2 (TPH1 and TPH2). We predicted that attentional bias and impulsivity would be higher in cocaine dependent individuals who had lower serotonin function. In the current study, we found a significant association between TPH2 genotype and attentional bias for the second block of the cocaine Stroop task. There was also a significant association between average attentional bias and HTTLPR genotype in the cocaine dependent individuals. The HT2C receptor genotype and attentional bias in our study sample also showed a significant difference. We did not find a significant difference between the serotonin 2A receptor variants or the TPH1 variants and attentional bias in the cocaine dependent group. In conclusion, the current study suggests that serotonergic medications should be utilized as pharmacotherapeutic treatment for cocaine addiction. Our results indicate that TPH2, the serotonin transporter and 2C receptor should be targeted in such a way as to modulate both, leading to increased synaptic serotonin function. Advisors/Committee Members: Frederick G. Moeller, David A. Nielsen, Scott D. Lane.

Subjects/Keywords: cocaine dependence attentional bias serotonin polymorphisms impulsivity; Behavioral Neurobiology; Cognitive Neuroscience; Genetics

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Maili, L. (2011). COCAINE DEPENDENCE: THE ROLE OF SEROTONIN GENES IN. (Thesis). Texas Medical Center. Retrieved from https://digitalcommons.library.tmc.edu/utgsbs_dissertations/109

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Maili, Lorena. “COCAINE DEPENDENCE: THE ROLE OF SEROTONIN GENES IN.” 2011. Thesis, Texas Medical Center. Accessed February 26, 2021. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/109.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Maili, Lorena. “COCAINE DEPENDENCE: THE ROLE OF SEROTONIN GENES IN.” 2011. Web. 26 Feb 2021.

Vancouver:

Maili L. COCAINE DEPENDENCE: THE ROLE OF SEROTONIN GENES IN. [Internet] [Thesis]. Texas Medical Center; 2011. [cited 2021 Feb 26]. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/109.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Maili L. COCAINE DEPENDENCE: THE ROLE OF SEROTONIN GENES IN. [Thesis]. Texas Medical Center; 2011. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/109

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Texas Medical Center

4. Hansen, Bryan J. POPULATION CODING IN LAMINAR CORTICAL CIRCUITS.

Degree: PhD, 2012, Texas Medical Center

URL: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/225

► One of the fundamental questions in neuroscience is to understand how encoding of sensory inputs is distributed across neuronal networks in cerebral cortex to… (more)

▼ One of the fundamental questions in neuroscience is to understand how encoding of sensory inputs is distributed across neuronal networks in cerebral cortex to influence sensory processing and behavioral performance. The fact that the structure of neuronal networks is organized according to cortical layers raises the possibility that sensory information could be processed differently in distinct layers. The goal of my thesis research is to understand how laminar circuits encode information in their population activity, how the properties of the population code adapt to changes in visual input, and how population coding influences behavioral performance. To this end, we performed a series of novel experiments to investigate how sensory information in the primary visual cortex (V1) emerges across laminar cortical circuits. First, it is commonly known that the amount of information encoded by cortical circuits depends critically on whether or not nearby neurons exhibit correlations. We examined correlated variability in V1 circuits from a laminar-specific perspective and observed that cells in the input layer, which have only local projections, encode incoming stimuli optimally by exhibiting low correlated variability. In contrast, output layers, which send projections to other cortical and subcortical areas, encode information suboptimally by exhibiting large correlations. These results argue that neuronal populations in different cortical layers play different roles in network computations. Secondly, a fundamental feature of cortical neurons is their ability to adapt to changes in incoming stimuli. Understanding how adaptation emerges across cortical layers to influence information processing is vital for understanding efficient sensory coding. We examined the effects of adaptation, on the time-scale of a visual fixation, on network synchronization across laminar circuits. Specific to the superficial layers, we observed an increase in gamma-band (30-80 Hz) synchronization after adaptation that was correlated with an improvement in neuronal orientation discrimination performance. Thus, synchronization enhances sensory coding to optimize network processing across laminar circuits. Finally, we tested the hypothesis that individual neurons and local populations synchronize their activity in real-time to communicate information about incoming stimuli, and that the degree of synchronization influences behavioral performance. These analyses assessed for the first time the relationship between changes in laminar cortical networks involved in stimulus processing and behavioral performance. Advisors/Committee Members: Valentin Dragoi, Ph.D., Daniel J. Felleman, Ph.D., Anne Sereno, Ph.D..

Subjects/Keywords: Cortical layers Synchronization Correlated varability Visual cortex Adaptation; Medicine and Health Sciences; Systems Neuroscience

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Hansen, B. J. (2012). POPULATION CODING IN LAMINAR CORTICAL CIRCUITS. (Doctoral Dissertation). Texas Medical Center. Retrieved from https://digitalcommons.library.tmc.edu/utgsbs_dissertations/225

Chicago Manual of Style (16^th Edition):

Hansen, Bryan J. “POPULATION CODING IN LAMINAR CORTICAL CIRCUITS.” 2012. Doctoral Dissertation, Texas Medical Center. Accessed February 26, 2021. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/225.

MLA Handbook (7^th Edition):

Hansen, Bryan J. “POPULATION CODING IN LAMINAR CORTICAL CIRCUITS.” 2012. Web. 26 Feb 2021.

Vancouver:

Hansen BJ. POPULATION CODING IN LAMINAR CORTICAL CIRCUITS. [Internet] [Doctoral dissertation]. Texas Medical Center; 2012. [cited 2021 Feb 26]. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/225.

Council of Science Editors:

Hansen BJ. POPULATION CODING IN LAMINAR CORTICAL CIRCUITS. [Doctoral Dissertation]. Texas Medical Center; 2012. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/225

Texas Medical Center

5. Popnoe, Dawn Olivia. Feasibility of Using Virtual Unenhanced Images to Replace Pre-contrast Images in Multiphase Renal CT Examinations.

Degree: MS, 2015, Texas Medical Center

URL: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/600

► Multiphase renal CT exams are a commonly used imaging technique for the diagnosis of renal masses. The pre-contrast, or true unenhanced (TUE), image provides… (more)

▼ Multiphase renal CT exams are a commonly used imaging technique for the diagnosis of renal masses. The pre-contrast, or true unenhanced (TUE), image provides a baseline for enhancement measurements which is an important criteria used to characterize renal lesions, consequently it is crucial that CT numbers measured in TUE images be accurate. The purpose of this work is to assess the feasibility of replacing TUE with virtual unenhanced (VUE) images derived from DECT data in renal CT exams. Eliminating TUE image acquisition would reduce patient dose and increase patient throughput, improving clinical efficiency. A retrospective study was conducted for 60 consecutively selected patient exams. VUE and TUE images were compared qualitatively and the differences were tested using a Bayesian Hierarchical model. VUE images were found to be inferior to TUE images for visualization of major vessels and depiction of liver parenchyma. CT numbers were measured in the liver, spleen, spine, aorta, cystic lesions, subcutaneous fat, renal cortex and medulla, and the differences were tested with a Student’s paired t-test. There were significant differences between TUE and VUE measurements ( p-value > 0.05) in the spleen, spine, aorta, renal cortex, subcutaneous fat, and inferior vena cava. However, evaluation of the clinical relevance based on grayscale perceptibly indicated that the difference for the spleen and subcutaneous fat are not clinically meaningful. The rapid kVp-switching GE CT750HD scanner was used to assess enhancement accuracy when using VUE compare to TUE images as the baseline for enhancement calculations across a wide range of clinical scenarios simulated in a phantom study, and the results were analyzed using Bayesian Hierarchical models. For simulation of angiomyolipoma and benign cystic lesions, enhancement values were not significantly different. However, for simulation of Bosniak category II-IV lesions, differences in measured enhancement were found to be significant. Additionally, the effect of ASIR level used in image reconstruction was assessed, and found not to affect measured CT number using a mixed effects model. Differences in measured enhancement values for simulated borderline enhancing renal lesions demonstrate that replacement of TUE with VUE images is not feasible with the current iteration of the algorithm. Advisors/Committee Members: Kyle Jones, Dianna Cody, Cheenu Kappadath.

Subjects/Keywords: CT Dual Energy CT Multi-material decomposition Renal CT Virtual Unenhanced Imaging; Medicine and Health Sciences; Physics

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Popnoe, D. O. (2015). Feasibility of Using Virtual Unenhanced Images to Replace Pre-contrast Images in Multiphase Renal CT Examinations. (Thesis). Texas Medical Center. Retrieved from https://digitalcommons.library.tmc.edu/utgsbs_dissertations/600

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Popnoe, Dawn Olivia. “Feasibility of Using Virtual Unenhanced Images to Replace Pre-contrast Images in Multiphase Renal CT Examinations.” 2015. Thesis, Texas Medical Center. Accessed February 26, 2021. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/600.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Popnoe, Dawn Olivia. “Feasibility of Using Virtual Unenhanced Images to Replace Pre-contrast Images in Multiphase Renal CT Examinations.” 2015. Web. 26 Feb 2021.

Vancouver:

Popnoe DO. Feasibility of Using Virtual Unenhanced Images to Replace Pre-contrast Images in Multiphase Renal CT Examinations. [Internet] [Thesis]. Texas Medical Center; 2015. [cited 2021 Feb 26]. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/600.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Popnoe DO. Feasibility of Using Virtual Unenhanced Images to Replace Pre-contrast Images in Multiphase Renal CT Examinations. [Thesis]. Texas Medical Center; 2015. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/600

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Texas Medical Center

6. Zhang, Lin. MICROENVIRONMENT-INDUCED PTEN LOSS BY EXOSOMAL MICRORNA PRIMES BRAIN METASTASIS OUTGROWTH.

Degree: PhD, 2016, Texas Medical Center

URL: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/710

► Development of life-threatening cancer metastases at distant organs requires disseminated tumor cells’ adaptation to and co-evolution with the drastically different microenvironments of metastatic sites.… (more)

▼ Development of life-threatening cancer metastases at distant organs requires disseminated tumor cells’ adaptation to and co-evolution with the drastically different microenvironments of metastatic sites. Cancer cells of common origin manifest distinct gene expression patterns after metastasizing to different organs. Clearly, the dynamic interplay between metastatic tumor cells and extrinsic signals at individual metastatic organ sites critically impacts the subsequent metastatic outgrowth. Yet, it is unclear when and how disseminated tumor cells acquire the essential traits from the microenvironment of metastatic organs that prime their subsequent outgrowth. Here we show that primary tumor cells with normal expression of PTEN, an important tumor suppressor, lose PTEN expression after dissemination to the brain, but not to other organs. PTEN level in PTEN-loss brain metastatic tumor cells is restored after leaving brain microenvironment. This brain microenvironment-dependent, reversible PTEN mRNA and protein down-regulation is epigenetically regulated by microRNAs (miRNAs) from astrocytes. Mechanistically, astrocyte-derived exosomes mediate an intercellular transfer of PTEN-targeting miRNAs to metastatic tumor cells, while astrocyte-specific depletion of PTEN-targeting miRNAs or blockade of astrocyte exosome secretion rescues the PTEN loss and suppresses brain metastasis in vivo. Furthermore, this adaptive PTEN loss in brain metastatic tumor cells leads to an increased secretion of cytokine chemokine (C-C motif) ligand 2 (CCL2), which recruits Iba1+ myeloid cells that reciprocally enhance outgrowth of brain metastatic tumor cells via enhanced proliferation and reduced apoptosis. Our findings demonstrate a remarkable plasticity of PTEN expression in metastatic tumor cells in response to different organ microenvironments, underpinning an essential role of co-evolution between the metastatic cells and their microenvironment during the adaptive metastatic outgrowth. Our findings signify the dynamic and reciprocal cross-talk between tumor cells and the metastatic niche; importantly, they provide new opportunities for effective anti-metastasis therapies, especially of consequence for those brain metastasis patients who are in dire need. Advisors/Committee Members: Dihua Yu, Mien-Chie Hung, Menashe Bar-Eli.

Subjects/Keywords: metastasis; tumor microenvironment; exosome; PTEN; microRNAs; brain metastasis; epigenetics; Biology; Cancer Biology; Cell Biology; Medicine and Health Sciences; Neoplasms

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Zhang, L. (2016). MICROENVIRONMENT-INDUCED PTEN LOSS BY EXOSOMAL MICRORNA PRIMES BRAIN METASTASIS OUTGROWTH. (Doctoral Dissertation). Texas Medical Center. Retrieved from https://digitalcommons.library.tmc.edu/utgsbs_dissertations/710

Chicago Manual of Style (16^th Edition):

Zhang, Lin. “MICROENVIRONMENT-INDUCED PTEN LOSS BY EXOSOMAL MICRORNA PRIMES BRAIN METASTASIS OUTGROWTH.” 2016. Doctoral Dissertation, Texas Medical Center. Accessed February 26, 2021. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/710.

MLA Handbook (7^th Edition):

Zhang, Lin. “MICROENVIRONMENT-INDUCED PTEN LOSS BY EXOSOMAL MICRORNA PRIMES BRAIN METASTASIS OUTGROWTH.” 2016. Web. 26 Feb 2021.

Vancouver:

Zhang L. MICROENVIRONMENT-INDUCED PTEN LOSS BY EXOSOMAL MICRORNA PRIMES BRAIN METASTASIS OUTGROWTH. [Internet] [Doctoral dissertation]. Texas Medical Center; 2016. [cited 2021 Feb 26]. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/710.

Council of Science Editors:

Zhang L. MICROENVIRONMENT-INDUCED PTEN LOSS BY EXOSOMAL MICRORNA PRIMES BRAIN METASTASIS OUTGROWTH. [Doctoral Dissertation]. Texas Medical Center; 2016. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/710

Texas Medical Center

7. Espejo, Alexsandra B. Role of phosphorylation in the regulation of PRMT5.

Degree: PhD, 2016, Texas Medical Center

URL: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/711

► PRMT5 is a member of a group of proteins that mediate arginine methylation. It is involved in diverse cellular processes, including cell differentiation, splicing,… (more)

▼ 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 number of residues, which prompted us to investigate whether phosphorylation of PRMT5 regulates its subcellular localization and/or substrate choice, by facilitating phospho-dependent protein-protein interactions. To study how phosphorylation affects PRMT5 function, protein microarrays were used to identify novel phosphodependent-interacting proteins. This analysis revealed that phosphorylation mediates the interaction of PRMT5 with several SH2-domain containing proteins, 14-3-3 proteins and the FHA domain of MDC1. These novel phospho-dependent PRMT5 interactions suggest that crosstalk between kinases and arginine methyltransferases may play a pivotal role in modulating the different cellular functions of PRMT5. Additionally, we have found that the C-terminal region of PRMT5 has a recognition motif shared by PDZ domains and 14-3-3 proteins. In order to bind to this motif, 14-3-3 proteins require the C-terminus to be phosphorylated, while PDZ domain recognition is phospho-independent. From these data, a new regulatory mechanism that affects PRMT5 behavior was proposed; the action of kinases and phosphatases on PRMT5 may function as a switch to regulate interactions between 14-3-3 and PDZ domain-containing proteins. We additionally observed this paradigm with a number of proteins, suggesting that this phosphorylation dependent switch, regulating binding to 14-3-3 and PDZ domains, occurs in a wide range of protein-protein interactions. Among the recently discovered PDZ-binding partners, we have found that PRMT5 interacts with NHERF2, a membrane-associated protein that regulates the sodium ion exchanger NHE3. Through this interaction, PRMT5 is placed in close proximity to the membrane and therefore may regulate the influx of ions through selective ion channels. Overall, we hypothesize that the direct interaction of PRMT5 with selected partners mediates the appropriate localization of PRMT5, allowing it to methylate specific substrates. Physiological processes including muscle contraction, cell homeostasis and neurotransmission are controlled by the selective conduction of ions across cell membranes. Ion channels and exchangers are proteins that span cell membranes and form channels or pores, facilitating the movement of ions in and out of cells. Abnormal cellular response to the… Advisors/Committee Members: Mark Bedford, Ph.D., Taiping Chen, Ph.D., Sharon Y.R. Dent, Ph.D..

Subjects/Keywords: PRMT5; phosphorylation; interactions; domain; protein microarray; SH2; PDZ; 14-3-3; FHA; Molecular Biology

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Espejo, A. B. (2016). Role of phosphorylation in the regulation of PRMT5. (Doctoral Dissertation). Texas Medical Center. Retrieved from https://digitalcommons.library.tmc.edu/utgsbs_dissertations/711

Chicago Manual of Style (16^th Edition):

Espejo, Alexsandra B. “Role of phosphorylation in the regulation of PRMT5.” 2016. Doctoral Dissertation, Texas Medical Center. Accessed February 26, 2021. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/711.

MLA Handbook (7^th Edition):

Espejo, Alexsandra B. “Role of phosphorylation in the regulation of PRMT5.” 2016. Web. 26 Feb 2021.

Vancouver:

Espejo AB. Role of phosphorylation in the regulation of PRMT5. [Internet] [Doctoral dissertation]. Texas Medical Center; 2016. [cited 2021 Feb 26]. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/711.

Council of Science Editors:

Espejo AB. Role of phosphorylation in the regulation of PRMT5. [Doctoral Dissertation]. Texas Medical Center; 2016. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/711

Texas Medical Center

8. Walker, Christopher M. Novel Simulation to Avoid Bias in Measurement of Hyperpolarized Pyruvate: Demonstrated in Phantom and In Vivo.

Degree: PhD, 2016, Texas Medical Center

URL: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/712

► Dynamic nuclear polarization creates a transient hyperpolarized nuclear state that can dramatically increase the signal detected by magnetic resonance imaging. This signal increase allows… (more)

▼ 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 transient hyperpolarized state and the complexity inherent in biological systems. As more advanced imaging and measurement techniques are developed for imaging hyperpolarized substrates, it is critical to characterize their effect on any relevant quantitative measure. To assist in accurate quantitative measurement of hyperpolarized agents, an infrastructure where acquisition strategies can be developed, compared, optimized and validated was critically need. A novel simulation architecture was developed that combines classical chemical kinetics with the basic physics of nuclear magnetic resonance and couples them to multiple perfusion models. Simulation results showed that changes in the acquisition strategy used will affect the resulting quantification of chemical exchange rates and suggested that any bias that is imposed by the acquisition strategy can be avoided by using optimized pulse sequences. To validate these predictions, a phantom system was developed that allows controllable chemical conversion of hyperpolarized pyruvate into lactate with a variability less than 20%. Using this phantom system, studies showed that poorly optimized pulse sequences significantly reduced the measured value of the chemical exchange rates, whereas optimized pulse sequences showed no significant difference in chemical exchange measurements. In order to test simulation predictions for a perfused system, an animal cohort with orthotropic anaplastic thyroid cancer was scanned with multiple sequences. Again, optimized sequences showed no significant difference in measured exchange rates while poorly designed sequences significantly underestimated the exchange rates, which is consistent with the simulation results. These validation studies suggest that this simulation architecture will be a powerful tool for developing and optimizing acquisition and quantization methods for hyperpolarized magnetic resonance imaging. Advisors/Committee Members: James A. Bankson, John Hazle, Dawid Schellingerhout.

Subjects/Keywords: hyperpolarized; pyruvate; magnetic resoance; simulation; Analytical, Diagnostic and Therapeutic Techniques and Equipment; Medicine and Health Sciences; Other Physics

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Walker, C. M. (2016). Novel Simulation to Avoid Bias in Measurement of Hyperpolarized Pyruvate: Demonstrated in Phantom and In Vivo. (Doctoral Dissertation). Texas Medical Center. Retrieved from https://digitalcommons.library.tmc.edu/utgsbs_dissertations/712

Chicago Manual of Style (16^th Edition):

Walker, Christopher M. “Novel Simulation to Avoid Bias in Measurement of Hyperpolarized Pyruvate: Demonstrated in Phantom and In Vivo.” 2016. Doctoral Dissertation, Texas Medical Center. Accessed February 26, 2021. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/712.

MLA Handbook (7^th Edition):

Walker, Christopher M. “Novel Simulation to Avoid Bias in Measurement of Hyperpolarized Pyruvate: Demonstrated in Phantom and In Vivo.” 2016. Web. 26 Feb 2021.

Vancouver:

Walker CM. Novel Simulation to Avoid Bias in Measurement of Hyperpolarized Pyruvate: Demonstrated in Phantom and In Vivo. [Internet] [Doctoral dissertation]. Texas Medical Center; 2016. [cited 2021 Feb 26]. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/712.

Council of Science Editors:

Walker CM. Novel Simulation to Avoid Bias in Measurement of Hyperpolarized Pyruvate: Demonstrated in Phantom and In Vivo. [Doctoral Dissertation]. Texas Medical Center; 2016. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/712

Texas Medical Center

9. Niedzielski, Joshua S. INVESTIGATION OF RADIATION INJURY IN THE ESOPHAGUS FROM DEFINITIVE CHEMORADIATION THERAPY USING NOVEL IMAGING BIOMARKERS.

Degree: PhD, 2016, Texas Medical Center

URL: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/713

► Radiation injury in the esophagus occurs with high frequency from the treatment of non-small cell lung cancer (NSCLC). Radiation esophagitis is an acute normal… (more)

▼ Radiation injury in the esophagus occurs with high frequency from the treatment of non-small cell lung cancer (NSCLC). Radiation esophagitis is an acute normal tissue toxicity that negatively affects treatment efficacy by limiting dose and potentially interrupting radiation therapy. Clinical quantification of this toxicity is typically achieved by utilizing physician grading scales, assigning complication severity on an ordinal scale of symptom presentation and/or physician chosen interventions. These criteria are subjective in nature, both from the physician assigning the grade and the patient reporting the symptom. Furthermore, radiation therapy planning guidelines for the esophagus are derived from toxicity prediction models utilizing these subjective grading scores as complication endpoints. Not only does this schema of toxicity analysis leads to a lack of consistency between models from different study populations, and thereby radiation therapy planning recommendations for the esophagus, but inherent patient radiosensitivity is not considered, leading to suboptimal treatment regimens. The purpose of this work was to investigate radiation injury in the esophagus by first developing in-vivo imaging biomarkers of radiation-response in the esophagus using 4-dimensional computed tomography (4DCT) and ¹⁸fluorodeoxyglucose positron emission tomography (FDG-PET), separately. These imaging biomarkers were then compare with radiation esophagitis grade, using traditional and machine learning techniques, and shown to objectively quantify esophageal radiation toxicity. Metrics describing the esophageal radiation response from either imaging modality were strong classifiers of radiation esophagitis grade. Multivariate models to predict maximum esophagitis treatment grade (4DCT), and esophagitis symptom progression (FDG-PET) were developed and had strong performance for both scenarios. These imaging biomarkers were then used to comprehensively investigate the influence of dose-geometry and radiation type (photon or proton) on esophageal response. Using these radiation-response biomarkers in esophageal dose-response analysis, dose metrics with spatial information of esophageal dose coverage, (e.g. dose to a subregion of the esophagus with specific percent cross-sectional area coverage), as well as without spatial information, (traditional dose-volume histogram), was analyzed separately using machine learning methods. No detectable difference in response was observed when comparing dose metrics with and without spatial information. Statistical analysis showed no significant difference (p Inherent patient radiation sensitivity was investigated using esophageal expansion and delivered dose to the corresponding esophageal subregion. Cluster analysis was used to group patient patients based on their maximum expansion and delivered dose to the analyzed subregion of the esophagus. Patients clustered with proportionally higher expansion per delivered dose were considered radiosensitive. These… Advisors/Committee Members: Laurence Court, Jinzhong Yang, Mary Martel.

Subjects/Keywords: Radiation therapy; normal tissue toxicity; esophagitis; non small cell lung cancer; NTCP modelling; imaging biomarker; machine learning; functional imaging; 4DCT; FDG-PET; Other Medical Sciences

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Niedzielski, J. S. (2016). INVESTIGATION OF RADIATION INJURY IN THE ESOPHAGUS FROM DEFINITIVE CHEMORADIATION THERAPY USING NOVEL IMAGING BIOMARKERS. (Doctoral Dissertation). Texas Medical Center. Retrieved from https://digitalcommons.library.tmc.edu/utgsbs_dissertations/713

Chicago Manual of Style (16^th Edition):

Niedzielski, Joshua S. “INVESTIGATION OF RADIATION INJURY IN THE ESOPHAGUS FROM DEFINITIVE CHEMORADIATION THERAPY USING NOVEL IMAGING BIOMARKERS.” 2016. Doctoral Dissertation, Texas Medical Center. Accessed February 26, 2021. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/713.

MLA Handbook (7^th Edition):

Niedzielski, Joshua S. “INVESTIGATION OF RADIATION INJURY IN THE ESOPHAGUS FROM DEFINITIVE CHEMORADIATION THERAPY USING NOVEL IMAGING BIOMARKERS.” 2016. Web. 26 Feb 2021.

Vancouver:

Niedzielski JS. INVESTIGATION OF RADIATION INJURY IN THE ESOPHAGUS FROM DEFINITIVE CHEMORADIATION THERAPY USING NOVEL IMAGING BIOMARKERS. [Internet] [Doctoral dissertation]. Texas Medical Center; 2016. [cited 2021 Feb 26]. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/713.

Council of Science Editors:

Niedzielski JS. INVESTIGATION OF RADIATION INJURY IN THE ESOPHAGUS FROM DEFINITIVE CHEMORADIATION THERAPY USING NOVEL IMAGING BIOMARKERS. [Doctoral Dissertation]. Texas Medical Center; 2016. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/713

Texas Medical Center

10. Turner, Heather N. Cellular and genetic bases of cold nociception and nociceptive sensitization in Drosophila larvae.

Degree: PhD, 2016, Texas Medical Center

URL: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/714

► Organisms from flies to mammals utilize thermoreceptors to detect and respond to noxious thermal stimuli. Although much is understood about noxious heat avoidance, our… (more)

▼ 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 found larvae produce a mutually exclusive set of reactive behaviors to a defined noxious cold stimulus (3-12 ºC), including a full-body contraction and the bending of anterior and posterior segments to make a U-Shape. These behaviors are distinct from normal locomotion, responses to gentle touch, noxious heat or harsh mechanical stimuli. Through genetic manipulation, we found cold responses require specific classes of peripheral sensory neurons and receptors, which differ depending on the cold-evoked behavior. Our data indicates these cold-sensing neurons are multimodal, and the level of cellular activation determines the behavioral output to different stimuli. To study cold nociceptive sensitization, we used a "sunburn assay" which exposes the dorsal side of the larva to UV-damage, and found larvae display a dramatic shift in cold responses after injury. This behavioral shift requires similar sets of peripheral sensory neurons and receptors specific to each sensitized cold-evoked behavior. Lastly, we found the Tumor Necrosis Factor (TNF) and Tachykinin (Tk) pathways, both involved in sensitization to noxious heat, may also play a role UV-induced cold sensitization. We have established the first system to study noxious cold and cold sensitization in Drosophila. Our unique tool and assay will allow us to further uncover the conserved molecular and genetic players involved in this process. Advisors/Committee Members: Michael J. Galko, Ph.D., Edgar T. Walters, Ph.D., Howard Gutstein, M.D..

Subjects/Keywords: Drosophila; nociception; pain; thermosensation; cold; sensitization; neurons; TRP channels; genetics; neuroscience; Molecular and Cellular Neuroscience

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Turner, H. N. (2016). Cellular and genetic bases of cold nociception and nociceptive sensitization in Drosophila larvae. (Doctoral Dissertation). Texas Medical Center. Retrieved from https://digitalcommons.library.tmc.edu/utgsbs_dissertations/714

Chicago Manual of Style (16^th Edition):

Turner, Heather N. “Cellular and genetic bases of cold nociception and nociceptive sensitization in Drosophila larvae.” 2016. Doctoral Dissertation, Texas Medical Center. Accessed February 26, 2021. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/714.

MLA Handbook (7^th Edition):

Turner, Heather N. “Cellular and genetic bases of cold nociception and nociceptive sensitization in Drosophila larvae.” 2016. Web. 26 Feb 2021.

Vancouver:

Turner HN. Cellular and genetic bases of cold nociception and nociceptive sensitization in Drosophila larvae. [Internet] [Doctoral dissertation]. Texas Medical Center; 2016. [cited 2021 Feb 26]. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/714.

Council of Science Editors:

Turner HN. Cellular and genetic bases of cold nociception and nociceptive sensitization in Drosophila larvae. [Doctoral Dissertation]. Texas Medical Center; 2016. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/714

Texas Medical Center

11. MacLellan, Christopher James. Determination of Thermal Dose Model Parameters Using Magnetic Resonance Imaging.

Degree: PhD, 2016, Texas Medical Center

URL: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/715

► Magnetic Resonance Temperature Imaging (MRTI) is a powerful technique for noninvasively monitoring temperature during minimally invasive thermal therapy procedures. When coupled with thermal dose… (more)

Subjects/Keywords: Magnetic Resonance Imaging; Thermal Dose Modeling; Thermal Ablation; Laser Ablation; Arrhenius Parameters; Thermal Damage; Medicine and Health Sciences; Radiology

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

MacLellan, C. J. (2016). Determination of Thermal Dose Model Parameters Using Magnetic Resonance Imaging. (Doctoral Dissertation). Texas Medical Center. Retrieved from https://digitalcommons.library.tmc.edu/utgsbs_dissertations/715

Chicago Manual of Style (16^th Edition):

MacLellan, Christopher James. “Determination of Thermal Dose Model Parameters Using Magnetic Resonance Imaging.” 2016. Doctoral Dissertation, Texas Medical Center. Accessed February 26, 2021. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/715.

MLA Handbook (7^th Edition):

MacLellan, Christopher James. “Determination of Thermal Dose Model Parameters Using Magnetic Resonance Imaging.” 2016. Web. 26 Feb 2021.

Vancouver:

MacLellan CJ. Determination of Thermal Dose Model Parameters Using Magnetic Resonance Imaging. [Internet] [Doctoral dissertation]. Texas Medical Center; 2016. [cited 2021 Feb 26]. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/715.

Council of Science Editors:

MacLellan CJ. Determination of Thermal Dose Model Parameters Using Magnetic Resonance Imaging. [Doctoral Dissertation]. Texas Medical Center; 2016. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/715

Texas Medical Center

12. Glitza Oliva, Isabella C. LONG-TERM SURVIVAL IN METASTATIC MELANOMA PATIENTS WITH LEPTOMENINGEAL DISEASE TREATED WITH INTRATHECAL INTERLEUKIN-2.

Degree: MS, 2016, Texas Medical Center

URL: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/716

► BACKGROUND: Metastatic melanoma patients with leptomeningeal disease (LMD) have an extremely poor prognosis and a paucity of effective treatment options. We assessed the safety… (more)

Subjects/Keywords: melanoma; interleukin-2; intrathecal; leptomeningeal disease; Medicine and Health Sciences

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Glitza Oliva, I. C. (2016). LONG-TERM SURVIVAL IN METASTATIC MELANOMA PATIENTS WITH LEPTOMENINGEAL DISEASE TREATED WITH INTRATHECAL INTERLEUKIN-2. (Thesis). Texas Medical Center. Retrieved from https://digitalcommons.library.tmc.edu/utgsbs_dissertations/716

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Glitza Oliva, Isabella C. “LONG-TERM SURVIVAL IN METASTATIC MELANOMA PATIENTS WITH LEPTOMENINGEAL DISEASE TREATED WITH INTRATHECAL INTERLEUKIN-2.” 2016. Thesis, Texas Medical Center. Accessed February 26, 2021. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/716.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Glitza Oliva, Isabella C. “LONG-TERM SURVIVAL IN METASTATIC MELANOMA PATIENTS WITH LEPTOMENINGEAL DISEASE TREATED WITH INTRATHECAL INTERLEUKIN-2.” 2016. Web. 26 Feb 2021.

Vancouver:

Glitza Oliva IC. LONG-TERM SURVIVAL IN METASTATIC MELANOMA PATIENTS WITH LEPTOMENINGEAL DISEASE TREATED WITH INTRATHECAL INTERLEUKIN-2. [Internet] [Thesis]. Texas Medical Center; 2016. [cited 2021 Feb 26]. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/716.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Glitza Oliva IC. LONG-TERM SURVIVAL IN METASTATIC MELANOMA PATIENTS WITH LEPTOMENINGEAL DISEASE TREATED WITH INTRATHECAL INTERLEUKIN-2. [Thesis]. Texas Medical Center; 2016. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/716

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Texas Medical Center

13. Gloston, Gabrielle F. The Role of Two Homologous E3 Ligases in Muscle Physiology.

Degree: MS, 2016, Texas Medical Center

URL: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/717

► 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… (more)

Subjects/Keywords: FBXL3; FBXL21; E3 ligases; circadian; muscle; protein degradation; Life Sciences; Medicine and Health Sciences

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Gloston, G. F. (2016). The Role of Two Homologous E3 Ligases in Muscle Physiology. (Thesis). Texas Medical Center. Retrieved from https://digitalcommons.library.tmc.edu/utgsbs_dissertations/717

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Gloston, Gabrielle F. “The Role of Two Homologous E3 Ligases in Muscle Physiology.” 2016. Thesis, Texas Medical Center. Accessed February 26, 2021. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/717.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Gloston, Gabrielle F. “The Role of Two Homologous E3 Ligases in Muscle Physiology.” 2016. Web. 26 Feb 2021.

Vancouver:

Gloston GF. The Role of Two Homologous E3 Ligases in Muscle Physiology. [Internet] [Thesis]. Texas Medical Center; 2016. [cited 2021 Feb 26]. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/717.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Gloston GF. The Role of Two Homologous E3 Ligases in Muscle Physiology. [Thesis]. Texas Medical Center; 2016. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/717

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Texas Medical Center

14. Herold, Jennifer L. THE ROLE OF STREPTOCOCCUS GALLOLYTICUS SUBSPECIES GALLOLYTICUS IN COLON CANCER DEVELOPMENT.

Degree: PhD, 2016, Texas Medical Center

URL: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/718

► Colorectal cancer (CRC) is the third most common cancer in men and women and is also the third most common cause of cancer death.… (more)

Subjects/Keywords: Colorectal cancer; microbiome; Streptococcus gallolyticus; Streptococcus bovis; β-catenin; tumorigenesis; Bacteriology; Cancer Biology; Medicine and Health Sciences

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Herold, J. L. (2016). THE ROLE OF STREPTOCOCCUS GALLOLYTICUS SUBSPECIES GALLOLYTICUS IN COLON CANCER DEVELOPMENT. (Doctoral Dissertation). Texas Medical Center. Retrieved from https://digitalcommons.library.tmc.edu/utgsbs_dissertations/718

Chicago Manual of Style (16^th Edition):

Herold, Jennifer L. “THE ROLE OF STREPTOCOCCUS GALLOLYTICUS SUBSPECIES GALLOLYTICUS IN COLON CANCER DEVELOPMENT.” 2016. Doctoral Dissertation, Texas Medical Center. Accessed February 26, 2021. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/718.

MLA Handbook (7^th Edition):

Herold, Jennifer L. “THE ROLE OF STREPTOCOCCUS GALLOLYTICUS SUBSPECIES GALLOLYTICUS IN COLON CANCER DEVELOPMENT.” 2016. Web. 26 Feb 2021.

Vancouver:

Herold JL. THE ROLE OF STREPTOCOCCUS GALLOLYTICUS SUBSPECIES GALLOLYTICUS IN COLON CANCER DEVELOPMENT. [Internet] [Doctoral dissertation]. Texas Medical Center; 2016. [cited 2021 Feb 26]. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/718.

Council of Science Editors:

Herold JL. THE ROLE OF STREPTOCOCCUS GALLOLYTICUS SUBSPECIES GALLOLYTICUS IN COLON CANCER DEVELOPMENT. [Doctoral Dissertation]. Texas Medical Center; 2016. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/718

Texas Medical Center

15. Tito, Antonio Joel, Jr. Characterization of Vesicular Monoamine Transporter 2 and its role in Parkinson's Disease Pathogenesis using Drosophila.

Degree: PhD, 2016, Texas Medical Center

URL: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/719

► 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… (more)

▼ 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 selective loss of DA neurons is still not known. Notably, dopamine (DA) itself is a chemically labile molecule and can become oxidized to toxic by-products while induce the accumulation of harmful molecules such as Reactive Oxygen Species (ROS). Accordingly, DA toxicity has long been suspected to play a role in selective neuronal loss in PD. Vesicular Monoamine Transporter (VMAT) is essential for proper vesicular storage of monoamines such as DA and their regulated release. Increasing evidence have linked VMAT dysfunction with Parkinson’s disease. In this study, we re-examine the gain- and loss-of-function phenotypes of the sole VMAT homologue in Drosophila. Our results suggest that the C-terminal sequences in the two encoded VMAT isoforms not only determine their differential subcellular localizations, but also their activities in content release. In particular, VMAT2 orthologue potentially poses a unique, previously unexplored activity in promoting DA release. On the other hand, by examining DA distribution in wildtype and VMAT mutant animals, we find that there exists intrinsic difference in the dynamics of intracellular DA handling among DA neurons clustered in different brain regions. Furthermore, loss of VMAT causes severe loss of total DA levels and a redistribution of DA in Drosophila brain. Lastly, removal of both VMAT and another PD gene parkin, which is also conserved in Drosophila, results in the selective loss of DA neurons, primarily in the protocerebral anterior medial (PAM) clusters of the brain. Our results suggest a potential involvement of cytoplasmic DA in selective degeneration of DA neurons and also implicating a role for a differential intracellular DA handling mechanism underlying the regional specificity of neuronal loss in PD patients. Advisors/Committee Members: Sheng Zhang, Ph.D., Richard Behringer, Ph.D., Hugo Bellen, Ph.D..

Subjects/Keywords: Neuroscience; Neurodegenerative Disease; Drosophila; Brain; Dopamine Neurons; Dopamine; Parkinson's Disease; Parkin; VMAT; Cell Biology; Medicine and Health Sciences; Molecular and Cellular Neuroscience; Molecular Biology; Molecular Genetics

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Tito, Antonio Joel, J. (2016). Characterization of Vesicular Monoamine Transporter 2 and its role in Parkinson's Disease Pathogenesis using Drosophila. (Doctoral Dissertation). Texas Medical Center. Retrieved from https://digitalcommons.library.tmc.edu/utgsbs_dissertations/719

Chicago Manual of Style (16^th Edition):

Tito, Antonio Joel, Jr. “Characterization of Vesicular Monoamine Transporter 2 and its role in Parkinson's Disease Pathogenesis using Drosophila.” 2016. Doctoral Dissertation, Texas Medical Center. Accessed February 26, 2021. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/719.

MLA Handbook (7^th Edition):

Tito, Antonio Joel, Jr. “Characterization of Vesicular Monoamine Transporter 2 and its role in Parkinson's Disease Pathogenesis using Drosophila.” 2016. Web. 26 Feb 2021.

Vancouver:

Tito, Antonio Joel J. Characterization of Vesicular Monoamine Transporter 2 and its role in Parkinson's Disease Pathogenesis using Drosophila. [Internet] [Doctoral dissertation]. Texas Medical Center; 2016. [cited 2021 Feb 26]. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/719.

Council of Science Editors:

Tito, Antonio Joel J. Characterization of Vesicular Monoamine Transporter 2 and its role in Parkinson's Disease Pathogenesis using Drosophila. [Doctoral Dissertation]. Texas Medical Center; 2016. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/719

Texas Medical Center

16. Dominguez, Emily. USING MOUSE MODELS TO DEFINE HOW THE P53 R72P POLYMORPHISM IMPACTS THE ADVERSE EFFECTS OF DOXORUBICIN AND IONIZING RADIATION.

Degree: PhD, 2016, Texas Medical Center

URL: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/720

► The single nucleotide polymorphism (SNP) at codon 72 of the tumor suppressor gene p53 codes for either an arginine (R) or proline (P) (p53… (more)

Subjects/Keywords: mouse models; p53; single nucleotide polymorphism; genotoxins; Cell Biology; Genetics and Genomics; Medicine and Health Sciences; Other Pharmacology, Toxicology and Environmental Health

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Dominguez, E. (2016). USING MOUSE MODELS TO DEFINE HOW THE P53 R72P POLYMORPHISM IMPACTS THE ADVERSE EFFECTS OF DOXORUBICIN AND IONIZING RADIATION. (Doctoral Dissertation). Texas Medical Center. Retrieved from https://digitalcommons.library.tmc.edu/utgsbs_dissertations/720

Chicago Manual of Style (16^th Edition):

Dominguez, Emily. “USING MOUSE MODELS TO DEFINE HOW THE P53 R72P POLYMORPHISM IMPACTS THE ADVERSE EFFECTS OF DOXORUBICIN AND IONIZING RADIATION.” 2016. Doctoral Dissertation, Texas Medical Center. Accessed February 26, 2021. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/720.

MLA Handbook (7^th Edition):

Dominguez, Emily. “USING MOUSE MODELS TO DEFINE HOW THE P53 R72P POLYMORPHISM IMPACTS THE ADVERSE EFFECTS OF DOXORUBICIN AND IONIZING RADIATION.” 2016. Web. 26 Feb 2021.

Vancouver:

Dominguez E. USING MOUSE MODELS TO DEFINE HOW THE P53 R72P POLYMORPHISM IMPACTS THE ADVERSE EFFECTS OF DOXORUBICIN AND IONIZING RADIATION. [Internet] [Doctoral dissertation]. Texas Medical Center; 2016. [cited 2021 Feb 26]. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/720.

Council of Science Editors:

Dominguez E. USING MOUSE MODELS TO DEFINE HOW THE P53 R72P POLYMORPHISM IMPACTS THE ADVERSE EFFECTS OF DOXORUBICIN AND IONIZING RADIATION. [Doctoral Dissertation]. Texas Medical Center; 2016. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/720

Texas Medical Center

17. Dhupkar, Pooja, 3012359. TARGETING PD-1/PDL-1 SIGNALING IN THE TREATMENT OF OSTEOSARCOMA LUNG METASTASIS.

Degree: PhD, 2016, Texas Medical Center

URL: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/721

► Osteosarcoma (OS) manifests itself as pulmonary metastasis, which is a major cause of death in OS patients. Novel treatments like immunotherapy hold promise for… (more)

▼ 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. We demonstrated that PDL-1 is expressed in human OS cell lines and in lung metastases from OS patients, implying that its importance as a potential therapeutic target in OS. Further, in vivo anti-murine-PD-1 administration led to a significant decrease in the number of OS lung metastases using a human LM7 OS mouse model. Also, there was a significant increase in tumor cell apoptosis and decrease in tumor cell proliferation after in vivo anti-PD-1 treatment. In addition, anti-PD-1 led to blockade of p-STAT3/p-Erk1/2 and PDL-1 signaling in OS lung tumors. We discovered that PD-1 was expressed on NK cells and macrophages in OS lung tumors. Increased infiltration of NK cells and macrophages was observed within OS lung metastatic tumors after anti-PD-1 treatment. Particularly, anti-PD-1 caused an increase in the anti-tumor M1 macrophages and decrease in numbers of pro-inflammatory M2 macrophages in OS lung metastases. We further investigated the implication of NK cells and macrophages in the therapeutic efficacy of anti-PD-1 against OS lung metastases. NK cell depletion using anti-asialo-GM1 did not affect the efficacy of anti-PD-1. Hence, NK cells were not the crucial immune cells involved in anti-tumor responses of anti-PD-1. However, macrophage depletion using Clodrosome prior to anti-PD-1 treatment significantly compromised the regression of OS lung metastasis. Our results implied that macrophages are the crucial mediators of the anti-tumor responses of anti-PD-1 against OS lung metastasis. Overall, our data suggests that PD-1 blockade with anti-PD-1 leads to regression of OS lung metastases, primarily through activation of macrophages. Advisors/Committee Members: Dr. Eugenie Kleinerman, Dr. Nancy Gordon, Dr. Zahid Siddik.

Subjects/Keywords: Programmed death ligand 1 (PDL-1); osteosarcoma; lung metastasis; immunotherapy; macrophages; Life Sciences

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Dhupkar, Pooja, 3. (2016). TARGETING PD-1/PDL-1 SIGNALING IN THE TREATMENT OF OSTEOSARCOMA LUNG METASTASIS. (Doctoral Dissertation). Texas Medical Center. Retrieved from https://digitalcommons.library.tmc.edu/utgsbs_dissertations/721

Chicago Manual of Style (16^th Edition):

Dhupkar, Pooja, 3012359. “TARGETING PD-1/PDL-1 SIGNALING IN THE TREATMENT OF OSTEOSARCOMA LUNG METASTASIS.” 2016. Doctoral Dissertation, Texas Medical Center. Accessed February 26, 2021. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/721.

MLA Handbook (7^th Edition):

Dhupkar, Pooja, 3012359. “TARGETING PD-1/PDL-1 SIGNALING IN THE TREATMENT OF OSTEOSARCOMA LUNG METASTASIS.” 2016. Web. 26 Feb 2021.

Vancouver:

Dhupkar, Pooja 3. TARGETING PD-1/PDL-1 SIGNALING IN THE TREATMENT OF OSTEOSARCOMA LUNG METASTASIS. [Internet] [Doctoral dissertation]. Texas Medical Center; 2016. [cited 2021 Feb 26]. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/721.

Council of Science Editors:

Dhupkar, Pooja 3. TARGETING PD-1/PDL-1 SIGNALING IN THE TREATMENT OF OSTEOSARCOMA LUNG METASTASIS. [Doctoral Dissertation]. Texas Medical Center; 2016. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/721

Texas Medical Center

18. HUANG, KAI-LIEH. THE ROLE OF PHOSPHORYLATION IN PAM2 MOTIF-CONTAINING PROTEINS MEDIATED MESSENGER RNA DEADENYLATION.

Degree: PhD, 2016, Texas Medical Center

URL: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/722

► Phosphorylation regulates many cellular processes. However, its role in mRNA deadenylation, a process to remove poly adenosines from the mature mRNA 3’ end tail,… (more)

▼ Phosphorylation regulates many cellular processes. However, its role in mRNA deadenylation, a process to remove poly adenosines from the mature mRNA 3’ end tail, is unclear. The length of poly(A) tail determines mRNA stability and translation efficiency. Poly(A)-binding protein (PABP), which binds to newly synthesized poly(A) tails homogeneously and is known as a scaffold protein for PAM2 motif-containing proteins, plays a pivotal role in the shortening of poly (A) tails. This study is to examine the role of phosphorylation of PAM2 motif–containing proteins in regulating their interactions with PABP and mRNA deadenylation function. The PAM2 motif, a region required for binding PABP C-terminal domain, is embedded inside the intrinsically disordered region (IDR) of its containing proteins. IDR is known to be a favored site for phosphorylation, and the PAM2 motif is surrounded by numerous potential phosphorylation sites. To test whether phosphorylation plays a role in controlling the interaction between PAM2-containing proteins and PABP, this study used complementary approaches (to alter the phosphorylation level of PAM2 motif-containing proteins biochemically and to create phospho-mimetic (PM) and non-phosphorylatable (NP) mutants). The results showed that reducing or increasing phosphorylation of these proteins can enhance or diminish their interaction with PABP, respectively. Furthermore, diminished PABP interaction compromises the biological functions of these proteins in deadenylation and miRNA-mediated gene silencing. Using Tob2-PABP interaction as a model, this study provides more insight into the mechanism by which phosphorylation of PAM2 motif–containing proteins regulates their interactions with PABP. The data presented here suggest that the two PAM2 motifs of Tob2 interact with PABP in a synergistic rather than addictive manner. Multiple phosphorylation induced by JNK1 in Tob2 IDR compromises Tob2-PABP interaction. A critical site for phosphorylation of Tob2 was identified. Global mRNA deadenylation can be regulated by phosphorylation status of this site. Collectively, this work provides a new concept, in which signaling pathways crosstalk may tune global deadenylation rates through phosphorylation of PAM2 motif-containing proteins to modify their PABP affinity. Advisors/Committee Members: Ann-Bin Shyu, Ph.D., Zheng Chen, Ph.D., Jianping Jin, Ph.D..

Subjects/Keywords: mRNA deadenylation; PAM2 motif; Phosphorylation; Intrinsically disordered regions; PABP; Tob2; Pan3; Tnrc6c; JNK; CDK; Biochemistry; Molecular Biology

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

HUANG, K. (2016). THE ROLE OF PHOSPHORYLATION IN PAM2 MOTIF-CONTAINING PROTEINS MEDIATED MESSENGER RNA DEADENYLATION. (Doctoral Dissertation). Texas Medical Center. Retrieved from https://digitalcommons.library.tmc.edu/utgsbs_dissertations/722

Chicago Manual of Style (16^th Edition):

HUANG, KAI-LIEH. “THE ROLE OF PHOSPHORYLATION IN PAM2 MOTIF-CONTAINING PROTEINS MEDIATED MESSENGER RNA DEADENYLATION.” 2016. Doctoral Dissertation, Texas Medical Center. Accessed February 26, 2021. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/722.

MLA Handbook (7^th Edition):

HUANG, KAI-LIEH. “THE ROLE OF PHOSPHORYLATION IN PAM2 MOTIF-CONTAINING PROTEINS MEDIATED MESSENGER RNA DEADENYLATION.” 2016. Web. 26 Feb 2021.

Vancouver:

HUANG K. THE ROLE OF PHOSPHORYLATION IN PAM2 MOTIF-CONTAINING PROTEINS MEDIATED MESSENGER RNA DEADENYLATION. [Internet] [Doctoral dissertation]. Texas Medical Center; 2016. [cited 2021 Feb 26]. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/722.

Council of Science Editors:

HUANG K. THE ROLE OF PHOSPHORYLATION IN PAM2 MOTIF-CONTAINING PROTEINS MEDIATED MESSENGER RNA DEADENYLATION. [Doctoral Dissertation]. Texas Medical Center; 2016. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/722

Texas Medical Center

19. Fletcher, Eliot S. ORGAN SPECIFIC VASCULAR RESPONSE TO FIBROSIS AFFECTS BREAST CANCER METASTATIC ORGANOTROPISM.

Degree: PhD, 2016, Texas Medical Center

URL: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/723

► 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… (more)

▼ 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 and metastasis it is also well characterized that primary tumor metastasis has specific organotropism, for example breast cancer commonly spreads to the lungs, brain, bone, liver and lymph nodes. However, whether non-organtropic fibrosis can redirect metastasis to the damaged organ has not been investigated. To elucidate the fibrotic effect on tumor organotropism we induced fibrosis in the organotropic lungs and in the non-organotropic kidney of two mouse models of breast cancer, the 4T1 murine cancer cell line model and the genetic MMTV-Pymt model, both of which are known to metastasize. Using histopathology, microarrays, gene expression by polymerase chain reaction, ELISA, chemokine array, and in vitro experiments we demonstrate that despite the pro-tumorigenic environment, kidney fibrosis does not redirect metastasis to the non-organotropic damaged organ. However, mice with kidney fibrosis had increased metastasis to their lungs. Furthermore, we found that kidney fibrosis increases the circulating levels of the pro-angiogenic factor Angiopoietin 2 that increased vascular permeability of the lungs, but not the kidneys. In fact, while fibrotic lungs showed decreased expression of endothelial tight gap junction protein Claudin-5, the fibrotic kidneys had an elevated expression of Claudin-5. Our findings suggest that despite the similarities between fibrosis, the tumor microenvironment and the pre-metastatic niche, that while it can enhance tropic metastatic disease, it cannot redirect organotropism indicating that other factors must be involved in directing organotropism. Here we report that tumor organotropism may be a result of organ specific vascular responses to excess circulating factors and increased fibrotic factors. These findings indicate that organotropism is directly related to and as a result of organ specific vascular alterations. Advisors/Committee Members: Raghu Kalluri, Valerie LeBleu, Menasche Bar Eli.

Subjects/Keywords: Medicine and Health Sciences

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Fletcher, E. S. (2016). ORGAN SPECIFIC VASCULAR RESPONSE TO FIBROSIS AFFECTS BREAST CANCER METASTATIC ORGANOTROPISM. (Doctoral Dissertation). Texas Medical Center. Retrieved from https://digitalcommons.library.tmc.edu/utgsbs_dissertations/723

Chicago Manual of Style (16^th Edition):

Fletcher, Eliot S. “ORGAN SPECIFIC VASCULAR RESPONSE TO FIBROSIS AFFECTS BREAST CANCER METASTATIC ORGANOTROPISM.” 2016. Doctoral Dissertation, Texas Medical Center. Accessed February 26, 2021. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/723.

MLA Handbook (7^th Edition):

Fletcher, Eliot S. “ORGAN SPECIFIC VASCULAR RESPONSE TO FIBROSIS AFFECTS BREAST CANCER METASTATIC ORGANOTROPISM.” 2016. Web. 26 Feb 2021.

Vancouver:

Fletcher ES. ORGAN SPECIFIC VASCULAR RESPONSE TO FIBROSIS AFFECTS BREAST CANCER METASTATIC ORGANOTROPISM. [Internet] [Doctoral dissertation]. Texas Medical Center; 2016. [cited 2021 Feb 26]. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/723.

Council of Science Editors:

Fletcher ES. ORGAN SPECIFIC VASCULAR RESPONSE TO FIBROSIS AFFECTS BREAST CANCER METASTATIC ORGANOTROPISM. [Doctoral Dissertation]. Texas Medical Center; 2016. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/723

Texas Medical Center

20. RIvera-Valentin, Rocio K. Her4 Promotes a Stem-like Phenotype in Osteosarcoma.

Degree: PhD, 2016, Texas Medical Center

URL: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/724

► Metastatic disease to the lungs is the primary cause of death for patients with pediatric osteosarcoma (OS). OS has a high degree of heterogeneity… (more)

▼ Metastatic disease to the lungs is the primary cause of death for patients with pediatric osteosarcoma (OS). OS has a high degree of heterogeneity and genomic instability, making understanding the pathogenesis and drivers of metastasis of this disease challenging. In an effort to explain tumoral heterogeneity, the tumor initiating cell model (TIC) states that tumors are composed of cells that form the majority of the tumor and are terminally differentiated. This model however, attributes tumorigenesis, metastasis and chemoresistance to a distinct cell population with a stem-like phenotype that can be identified using selective markers. OS appears to follow this model where OS cells with tumor initiating potential can be identified by expression of Stro1, CD117 and embryonic stem cell transcription factors such as Sox2, Nanog and Oct3/4. Additionally, OS stem-like cells display high aldehyde dehydrogenase activity and sarcosphere formation under limited nutrient media and anchorage independence. These markers are not feasible targets for therapy due to their expression on normal tissue stem cells; however, upstream regulators of this phenotype may be targetable. Therefore, we investigated other modulators of the stem-like phenotype. Her4, a transmembrane receptor of the EGFR family, has been recently studied for its role in cancer. Previously, we demonstrated that Her4 is highly expressed in neuroblastoma, and OS, while others have shown its importance in Ewing sarcoma. This receptor is induced and required to survive stressors, like anchorage independence, serum starvation and chemotherapy treatment, which are similar in vitro conditions used to enrich for cells with tumor initiating potential. Therefore, we hypothesized that Her4 expression is an important regulator of a stem-like phenotype in OS. In sarcosphere culture, Her4 expression is induced and precedes the induction of CD117 and Stro1. OS cells with Her4 deleted by CRISPR/Cas9 have decreased aldehyde dehydrogenase activity and cannot upregulate the pluripotency transcription factors Sox2, Oct3/4 and Nanog even when in sarcospheres. Overexpression of exogenous Her4 was able to cause upregulation of these transcription factors and increase expression of CD117 in monolayer culture. We examined Her4 expression in OS diagnostic biopsies and determined the correlation with metastasis free survival. Tumors with high Her4 expression have higher probability of developing metastatic disease. In this dissertation, we demonstrate that Her4 expression is induced by conditions that enrich stem-like cells and its expression correlates with the ability to upregulate various OS TIC markers. Therefore, Her4 may contribute to pathogenesis of OS by conferring a stem-like phenotype. Advisors/Committee Members: Eugenie S. Kleinerman, MD, Nino Rainusso, MD, Candelaria Gomez-Manzano, MD.

Subjects/Keywords: osteosarcoma; stem-like phenotype; Her4; ERBB4; Oncology; Translational Medical Research

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

RIvera-Valentin, R. K. (2016). Her4 Promotes a Stem-like Phenotype in Osteosarcoma. (Doctoral Dissertation). Texas Medical Center. Retrieved from https://digitalcommons.library.tmc.edu/utgsbs_dissertations/724

Chicago Manual of Style (16^th Edition):

RIvera-Valentin, Rocio K. “Her4 Promotes a Stem-like Phenotype in Osteosarcoma.” 2016. Doctoral Dissertation, Texas Medical Center. Accessed February 26, 2021. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/724.

MLA Handbook (7^th Edition):

RIvera-Valentin, Rocio K. “Her4 Promotes a Stem-like Phenotype in Osteosarcoma.” 2016. Web. 26 Feb 2021.

Vancouver:

RIvera-Valentin RK. Her4 Promotes a Stem-like Phenotype in Osteosarcoma. [Internet] [Doctoral dissertation]. Texas Medical Center; 2016. [cited 2021 Feb 26]. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/724.

Council of Science Editors:

RIvera-Valentin RK. Her4 Promotes a Stem-like Phenotype in Osteosarcoma. [Doctoral Dissertation]. Texas Medical Center; 2016. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/724

Texas Medical Center

21. Mananadhar, Mandira. NUCLEOTIDE EXCISION REPAIR, CROSSLINK REPAIR AND TRANSCRIPTIONAL FUNCTION OF XPA IN HUMAN CELLS.

Degree: PhD, 2016, Texas Medical Center

URL: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/726

► Nucleotide excision repair (NER) in mammalian cells includes xeroderma pigmentosum group A protein (XPA) as a core factor. XPA and other NER proteins have… (more)

▼ Nucleotide excision repair (NER) in mammalian cells includes xeroderma pigmentosum group A protein (XPA) as a core factor. XPA and other NER proteins have been detected previously at some active promoters, and NER deficiency is reported to decrease activated transcription of selected genes. To determine the global extent of XPA influence on transcription, we analyzed the human transcriptome by RNA sequencing. We first confirmed that XPA is confined to the cell nucleus even in the absence of external DNA damage, in contrast to previous reports that XPA is normally resident in the cytoplasm and is imported following DNA damage. We then analyzed four genetically matched human cell line pairs deficient or proficient in XPA. At a false discovery rate of 0.05, 325 genes were common in all four pairs with a significant XPA-dependent directional change in gene expression. These genes were highly represented in pathways for the maintenance of mitochondria, metabolism and neurological system. Only 27 genes were regulated by more than 1.5 fold change. The most significant hits were AKR1C1 and AKR1C2, involved in steroid hormone metabolism, and the corresponding proteins were lower in XPA-deficient cells. Transactivation by retinoic acid caused a modest enrichment of genes involved in transcription-related functions in XPA proficient cells. The results show that XPA status significantly influences a small subset of human genes that are important for mitochondrial and metabolic functions. The results may help explain defects in neurological function and sterility in individuals with xeroderma pigmentosum (XP). An NER deficiency enhances sensitivity of mammalian cells to DNA interstrand crosslinks (ICL)-generating agents. I found that XPA is retained on damaged DNA following exposure to UVA-activated psoralen, and investigated repair of a triplex forming oligonucleotide (TFO)-directed psoralen ICL. A TFO-directed psoralen DNA ICL was constructed in closed-circular DNA. In NER proficient human cell extracts, incisions were detected on both strands of the damaged DNA 3’ to the psoralen ICL. Incision sites on the TFO bound strand were flanked by incision sites 40-42 nucleotides away from the ICL, with incisions 10-12 nucleotides away on the other strand. Advisors/Committee Members: Richard D. Wood, PhD, Karen M. Vasquez, PhD, Mark T. Bedford, PhD.

Subjects/Keywords: Nucleotide excision repair; XPA; Interstrand crosslink; Transcription; DNA repair; Medicine and Health Sciences

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Mananadhar, M. (2016). NUCLEOTIDE EXCISION REPAIR, CROSSLINK REPAIR AND TRANSCRIPTIONAL FUNCTION OF XPA IN HUMAN CELLS. (Doctoral Dissertation). Texas Medical Center. Retrieved from https://digitalcommons.library.tmc.edu/utgsbs_dissertations/726

Chicago Manual of Style (16^th Edition):

Mananadhar, Mandira. “NUCLEOTIDE EXCISION REPAIR, CROSSLINK REPAIR AND TRANSCRIPTIONAL FUNCTION OF XPA IN HUMAN CELLS.” 2016. Doctoral Dissertation, Texas Medical Center. Accessed February 26, 2021. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/726.

MLA Handbook (7^th Edition):

Mananadhar, Mandira. “NUCLEOTIDE EXCISION REPAIR, CROSSLINK REPAIR AND TRANSCRIPTIONAL FUNCTION OF XPA IN HUMAN CELLS.” 2016. Web. 26 Feb 2021.

Vancouver:

Mananadhar M. NUCLEOTIDE EXCISION REPAIR, CROSSLINK REPAIR AND TRANSCRIPTIONAL FUNCTION OF XPA IN HUMAN CELLS. [Internet] [Doctoral dissertation]. Texas Medical Center; 2016. [cited 2021 Feb 26]. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/726.

Council of Science Editors:

Mananadhar M. NUCLEOTIDE EXCISION REPAIR, CROSSLINK REPAIR AND TRANSCRIPTIONAL FUNCTION OF XPA IN HUMAN CELLS. [Doctoral Dissertation]. Texas Medical Center; 2016. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/726

Texas Medical Center

22. Vila, Ph.D., Alejandro. MAGUK SCAFFOLDS ORGANIZE A KEY SYNAPTIC COMPLEX IN HORIZONTAL CELL PROCESSES CONTACTING PHOTORECEPTORS.

Degree: PhD, 2016, Texas Medical Center

URL: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/727

► Synaptic processes and plasticity of synapses are mediated by large suites of proteins. In most cases, many of these proteins are tethered together by… (more)

▼ 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 the tips of B-type horizontal cell processes where they contact cone and rod photoreceptors. We further identified some known SAP102 binding partners, kainate receptor GluR6/7 and inward rectifier potassium channel Kir2.1, closely associated with SAP102 in the processes of invaginating HCs. In contrast, in the mouse retina we identified Chapsyn110 as the major scaffold in the tips of horizontal cells contacting photoreceptors. Kir2.1 was found to be assembled with SAP102 into a complex with GluR6/7 in photoreceptor invaginations in Rabbit. GluR6/7 and Kir2.1 presumably are involved in synaptic processes that govern cell-to-cell communication, and could both contribute in different ways to synaptic currents that mediate feedback signaling. Notably, we failed to find evidence for the presence of Cx57 or Cx59, but Pannexin1 immunolabeling was positive in the OPL of mouse retina suggesting that it could play a role in ephaptic and pH mediated signaling. Polyamines regulate many ion channels including Kir2.1. During the day polyamine immunolabeling was unexpectedly high in photoreceptor terminals compared to other areas of the retina. If polyamines are released, they may regulate the activity of Kir2.1 channels located in the tips of HCs. Alternatively, the presence of polyamines may potentiate GluR6/7 by reducing the transition to desensitized state causing an increase in channel conductance. The presence of SAP102 and Chapsyn110 and their binding partners in both cone and rod invaginating synapses suggests that whatever mechanism is supported by this protein complex is present in both types of photoreceptors. Advisors/Committee Members: John O'Brien, Stephen Mills, Christophe Ribelayga.

Subjects/Keywords: Dlg3; Dlg2; Kcnj2; Grik2; synaptic signaling; proximity ligation assays; Medicine and Health Sciences; Molecular and Cellular Neuroscience; Systems Neuroscience

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Vila, Ph.D., A. (2016). MAGUK SCAFFOLDS ORGANIZE A KEY SYNAPTIC COMPLEX IN HORIZONTAL CELL PROCESSES CONTACTING PHOTORECEPTORS. (Doctoral Dissertation). Texas Medical Center. Retrieved from https://digitalcommons.library.tmc.edu/utgsbs_dissertations/727

Chicago Manual of Style (16^th Edition):

Vila, Ph.D., Alejandro. “MAGUK SCAFFOLDS ORGANIZE A KEY SYNAPTIC COMPLEX IN HORIZONTAL CELL PROCESSES CONTACTING PHOTORECEPTORS.” 2016. Doctoral Dissertation, Texas Medical Center. Accessed February 26, 2021. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/727.

MLA Handbook (7^th Edition):

Vila, Ph.D., Alejandro. “MAGUK SCAFFOLDS ORGANIZE A KEY SYNAPTIC COMPLEX IN HORIZONTAL CELL PROCESSES CONTACTING PHOTORECEPTORS.” 2016. Web. 26 Feb 2021.

Vancouver:

Vila, Ph.D. A. MAGUK SCAFFOLDS ORGANIZE A KEY SYNAPTIC COMPLEX IN HORIZONTAL CELL PROCESSES CONTACTING PHOTORECEPTORS. [Internet] [Doctoral dissertation]. Texas Medical Center; 2016. [cited 2021 Feb 26]. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/727.

Council of Science Editors:

Vila, Ph.D. A. MAGUK SCAFFOLDS ORGANIZE A KEY SYNAPTIC COMPLEX IN HORIZONTAL CELL PROCESSES CONTACTING PHOTORECEPTORS. [Doctoral Dissertation]. Texas Medical Center; 2016. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/727

Texas Medical Center

23. Pan, Rongqing. TARGETING APOPTOTIC PATHWAYS TO OVERCOME DRUG RESISTANCE IN ACUTE MYELOID LEUKEMIA.

Degree: PhD, 2017, Texas Medical Center

URL: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/728

► 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… (more)

▼ 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 efficacy of ABT-199. Despite the initial success, we find that MCL-1 protein renders cancer cells resistant to ABT-199. Next we investigated whether p53 activation could overcome MCL-1–mediated resistance to BCL-2 inhibitor ABT-199. We demonstrate that p53 activation by MDM2 inhibitor RG7388 effectively overcomes the acquired or inherent resistance to ABT-199 both in vitro and in vivo. Mechanistic studies indicate that ABT-199 induces stabilizing phosphorylation of MCL-1. Surprisingly, p53 activation mediates the conversion from stabilized MCL-1 to destabilized MCL-1. Further mechanistic studies demonstrate that p53 activation inhibits N-Ras/Raf/MEK/ERK signaling and releases GSK3 activity to modulate MCL-1 phosphorylation and promote Mcl-1 degradation. Additionally, p53 activation also induces pro-apoptotic proteins such as PUMA and BAX to counteract MCL-1, thus overcoming Mcl-1 mediated resistance at multiple levels. During the course of this study, we find that AML cells resistant to BCL-2 inhibition may also be resistant to p53 activation. We demonstrate that p53-induced p21^Cip1 protein confer tumor resistance by promoting reversible G1 arrest. Importantly, BCL-2 inhibition switches the outcomes of p53 activation from pro-survival G1 arrest to apoptosis, thus overcoming AML resistance to p53 activation. The combination of BCL-2 inhibition and p53 induction markedly prolongs survival in three resistant mouse models of AML. These results collectively indicate that p53 activation and BCL-2 inhibition reciprocally overcome apoptosis resistance to either strategy alone. Our study provides novel mechanistic insights into the mechanisms of apoptosis resistance and forms the concept for an international phase II trial in AML. Advisors/Committee Members: Michael Andreeff, Pierre McCrea, Marina Konopleva.

Subjects/Keywords: Mitochondrial apoptosis; Bcl-2 family proteins; Drug resistance; p53; MDM2; Mcl-1; G1 arrest; BH3 profiling; Acute myeloid leukemia; Biology; Cancer Biology; Cell and Developmental Biology; Life Sciences; Medicine and Health Sciences

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Pan, R. (2017). TARGETING APOPTOTIC PATHWAYS TO OVERCOME DRUG RESISTANCE IN ACUTE MYELOID LEUKEMIA. (Doctoral Dissertation). Texas Medical Center. Retrieved from https://digitalcommons.library.tmc.edu/utgsbs_dissertations/728

Chicago Manual of Style (16^th Edition):

Pan, Rongqing. “TARGETING APOPTOTIC PATHWAYS TO OVERCOME DRUG RESISTANCE IN ACUTE MYELOID LEUKEMIA.” 2017. Doctoral Dissertation, Texas Medical Center. Accessed February 26, 2021. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/728.

MLA Handbook (7^th Edition):

Pan, Rongqing. “TARGETING APOPTOTIC PATHWAYS TO OVERCOME DRUG RESISTANCE IN ACUTE MYELOID LEUKEMIA.” 2017. Web. 26 Feb 2021.

Vancouver:

Pan R. TARGETING APOPTOTIC PATHWAYS TO OVERCOME DRUG RESISTANCE IN ACUTE MYELOID LEUKEMIA. [Internet] [Doctoral dissertation]. Texas Medical Center; 2017. [cited 2021 Feb 26]. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/728.

Council of Science Editors:

Pan R. TARGETING APOPTOTIC PATHWAYS TO OVERCOME DRUG RESISTANCE IN ACUTE MYELOID LEUKEMIA. [Doctoral Dissertation]. Texas Medical Center; 2017. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/728

Texas Medical Center

24. hu, Xin. INTEGRATIVE ANALYSIS OF OMICS DATA IN ADULT GLIOMA AND OTHER TCGA CANCERS TO GUIDE PRECISION MEDICINE.

Degree: PhD, 2017, Texas Medical Center

URL: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/729

► Transcriptomic profiling and gene expression signatures have been widely applied as effective approaches for enhancing the molecular classification, diagnosis, prognosis or prediction of therapeutic… (more)

▼ Transcriptomic profiling and gene expression signatures have been widely applied as effective approaches for enhancing the molecular classification, diagnosis, prognosis or prediction of therapeutic response towards personalized therapy for cancer patients. Thanks to modern genome-wide profiling technology, scientists are able to build engines leveraging massive genomic variations and integrating with clinical data to identify “at risk” individuals for the sake of prevention, diagnosis and therapeutic interventions. In my graduate work for my Ph.D. thesis, I have investigated genomic sequencing data mining to comprehensively characterise molecular classifications and aberrant genomic events associated with clinical prognosis and treatment response, through applying high-dimensional omics genomic data to promote the understanding of gene signatures and somatic molecular alterations contributing to cancer progression and clinical outcomes. Following this motivation, my dissertation has been focused on the following three topics in translational genomics. 1) Characterization of transcriptomic plasticity and its association with the tumor microenvironment in glioblastoma (GBM). I have integrated transcriptomic, genomic, protein and clinical data to increase the accuracy of GBM classification, and identify the association between the GBM mesenchymal subtype and reduced tumorpurity, accompanied with increased presence of tumor-associated microglia. Then I have tackled the sole source of microglial as intrinsic tumor bulk but not their corresponding neurosphere cells through both transcriptional and protein level analysis using a panel of sphere-forming glioma cultures and their parent GBM samples.FurthermoreI have demonstrated my hypothesis through longitudinal analysis of paired primary and recurrent GBM samples that the phenotypic alterations of GBM subtypes are not due to intrinsic proneural-to-mesenchymal transition in tumor cells, rather it is intertwined with increased level of microglia upon disease recurrence. Collectively I have elucidated the critical role of tumor microenvironment (Microglia and macrophages from central nervous system) contributing to the intra-tumor heterogeneity and accurate classification of GBM patients based on transcriptomic profiling, which will not only significantly impact on clinical perspective but also pave the way for preclinical cancer research. 2) Identification of prognostic gene signatures that stratify adult diffuse glioma patientsharboring1p/19q co-deletions. I have compared multiple statistical methods and derived a gene signature significantly associated with survival by applying a machine learning algorithm. Then I have identified inflammatory response and acetylation activity that associated with malignant progression of 1p/19q co-deleted glioma. In addition, I showed this signature translates to other types of adult diffuse glioma, suggesting its universality in the pathobiology of other subset gliomas. My efforts on integrative data analysis of this… Advisors/Committee Members: Roel G.W. Verhaak, Ph.D., Erik P. Sulman, M.D., Ph.D., Keith A. Baggerly, Ph.D..

Subjects/Keywords: Cancer genomics; Omics data mining; Transcriptomics profiling; Gene signature; Risk prediction; Tumor microenvironment; Precision medicine; Glioma; Pan-cancer; Fusion transcripts; Genomic rearrangement; Next-generation sequencing; Prediction model; Disease Modeling; Health Information Technology; Medicine and Health Sciences; Translational Medical Research

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

hu, X. (2017). INTEGRATIVE ANALYSIS OF OMICS DATA IN ADULT GLIOMA AND OTHER TCGA CANCERS TO GUIDE PRECISION MEDICINE. (Doctoral Dissertation). Texas Medical Center. Retrieved from https://digitalcommons.library.tmc.edu/utgsbs_dissertations/729

Chicago Manual of Style (16^th Edition):

hu, Xin. “INTEGRATIVE ANALYSIS OF OMICS DATA IN ADULT GLIOMA AND OTHER TCGA CANCERS TO GUIDE PRECISION MEDICINE.” 2017. Doctoral Dissertation, Texas Medical Center. Accessed February 26, 2021. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/729.

MLA Handbook (7^th Edition):

hu, Xin. “INTEGRATIVE ANALYSIS OF OMICS DATA IN ADULT GLIOMA AND OTHER TCGA CANCERS TO GUIDE PRECISION MEDICINE.” 2017. Web. 26 Feb 2021.

Vancouver:

hu X. INTEGRATIVE ANALYSIS OF OMICS DATA IN ADULT GLIOMA AND OTHER TCGA CANCERS TO GUIDE PRECISION MEDICINE. [Internet] [Doctoral dissertation]. Texas Medical Center; 2017. [cited 2021 Feb 26]. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/729.

Council of Science Editors:

hu X. INTEGRATIVE ANALYSIS OF OMICS DATA IN ADULT GLIOMA AND OTHER TCGA CANCERS TO GUIDE PRECISION MEDICINE. [Doctoral Dissertation]. Texas Medical Center; 2017. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/729

Texas Medical Center

25. Wang, Pingping. PROTEOMIC IDENTIFICATION OF HISTONE POST-TRANSLATIONAL MODIFICATIONS INDUCED BY DNA DOUBLE-STRAND BREAKS AND NOVEL PROTEINS INVOLVED IN THE DNA DAMAGE RESPONSE.

Degree: PhD, 2017, Texas Medical Center

URL: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/731

► Inaccurate repair of DNA double-strand breaks (DSBs) can lead to DNA mutation and chromosome rearrangements, causing human diseases such as cancer. Although we know… (more)

Subjects/Keywords: DSB; PTM; Affinity Purification; Mass Spectrometry; Yeast; DNA repair; Checkpoint; Biology; Cell Biology; Life Sciences; Medicine and Health Sciences; Microbiology; Molecular Genetics

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Wang, P. (2017). PROTEOMIC IDENTIFICATION OF HISTONE POST-TRANSLATIONAL MODIFICATIONS INDUCED BY DNA DOUBLE-STRAND BREAKS AND NOVEL PROTEINS INVOLVED IN THE DNA DAMAGE RESPONSE. (Doctoral Dissertation). Texas Medical Center. Retrieved from https://digitalcommons.library.tmc.edu/utgsbs_dissertations/731

Chicago Manual of Style (16^th Edition):

Wang, Pingping. “PROTEOMIC IDENTIFICATION OF HISTONE POST-TRANSLATIONAL MODIFICATIONS INDUCED BY DNA DOUBLE-STRAND BREAKS AND NOVEL PROTEINS INVOLVED IN THE DNA DAMAGE RESPONSE.” 2017. Doctoral Dissertation, Texas Medical Center. Accessed February 26, 2021. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/731.

MLA Handbook (7^th Edition):

Wang, Pingping. “PROTEOMIC IDENTIFICATION OF HISTONE POST-TRANSLATIONAL MODIFICATIONS INDUCED BY DNA DOUBLE-STRAND BREAKS AND NOVEL PROTEINS INVOLVED IN THE DNA DAMAGE RESPONSE.” 2017. Web. 26 Feb 2021.

Vancouver:

Wang P. PROTEOMIC IDENTIFICATION OF HISTONE POST-TRANSLATIONAL MODIFICATIONS INDUCED BY DNA DOUBLE-STRAND BREAKS AND NOVEL PROTEINS INVOLVED IN THE DNA DAMAGE RESPONSE. [Internet] [Doctoral dissertation]. Texas Medical Center; 2017. [cited 2021 Feb 26]. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/731.

Council of Science Editors:

Wang P. PROTEOMIC IDENTIFICATION OF HISTONE POST-TRANSLATIONAL MODIFICATIONS INDUCED BY DNA DOUBLE-STRAND BREAKS AND NOVEL PROTEINS INVOLVED IN THE DNA DAMAGE RESPONSE. [Doctoral Dissertation]. Texas Medical Center; 2017. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/731

Texas Medical Center

26. Hunt, Albert J, Jr. The External Globus Pallidus: Bidirectional Control Over Anxiety-Related Behavior Mediated by CRFR1.

Degree: PhD, 2017, Texas Medical Center

URL: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/732

► <h1>Abstract</h1> THE EXTERNAL GLOBUS PALLIDUS: BIDIRECTIONAL CONTROL OVER ANXIETY-RELATED BEHAVIOR MEDIATED BY CRFR1 Albert Lee Joseph Hunt, Jr., B.S. Advisory Professor: Shane Cunha, Ph.D. Corticotropin-releasing… (more)

Subjects/Keywords: GPe; external globus pallidus; CRF; CRFR1; anxiety; behavior; mice; parkinson's disease; psychiatric; Medicine and Health Sciences

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Hunt, Albert J, J. (2017). The External Globus Pallidus: Bidirectional Control Over Anxiety-Related Behavior Mediated by CRFR1. (Doctoral Dissertation). Texas Medical Center. Retrieved from https://digitalcommons.library.tmc.edu/utgsbs_dissertations/732

Chicago Manual of Style (16^th Edition):

Hunt, Albert J, Jr. “The External Globus Pallidus: Bidirectional Control Over Anxiety-Related Behavior Mediated by CRFR1.” 2017. Doctoral Dissertation, Texas Medical Center. Accessed February 26, 2021. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/732.

MLA Handbook (7^th Edition):

Hunt, Albert J, Jr. “The External Globus Pallidus: Bidirectional Control Over Anxiety-Related Behavior Mediated by CRFR1.” 2017. Web. 26 Feb 2021.

Vancouver:

Hunt, Albert J J. The External Globus Pallidus: Bidirectional Control Over Anxiety-Related Behavior Mediated by CRFR1. [Internet] [Doctoral dissertation]. Texas Medical Center; 2017. [cited 2021 Feb 26]. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/732.

Council of Science Editors:

Hunt, Albert J J. The External Globus Pallidus: Bidirectional Control Over Anxiety-Related Behavior Mediated by CRFR1. [Doctoral Dissertation]. Texas Medical Center; 2017. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/732

Texas Medical Center

27. Kiany, Simin. EFFECT OF ENTINOSTAT ON NK CELL-MEDIATED CYTOTOXICITY AGAINST OS CELLS AND OS LUNG METASTSIS.

Degree: PhD, 2017, Texas Medical Center

URL: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/733

► The purpose of this study was to investigate the effect of the HDAC inhibitor entinostat on the efficacy of NK cell therapy for OS… (more)

▼ The purpose of this study was to investigate the effect of the HDAC inhibitor entinostat on the efficacy of NK cell therapy for OS lung metastasis. The Lung is the most common site of OS metastatic spread in OS and pulmonary metastasis is the main cause of mortality. We have previously demonstrated that NK cell therapy has minimal efficacy against OS metastasis. We wished to determine whether we could augment the killing of OS cells in vitro and improve the efficacy of NK cell therapy in vivo by adding oral administration of entinostat. We elected to use our nude mouse human OS lung metastasis model for this purpose. In vitro, entinostat increased NK cell ligands on OS cells (MIC A/B, ULBP1, ULBP2/5/6, and CD155) and enhanced the NK cell-mediated cytotoxicity. Entinostat oral administration also increased MICA/B expression on lung tumors. Entinostat (≤ 2 μM) did not have any adverse effect on NK cell viability, receptor expression, or function within the 24 h treatment. We demonstrated two potential mechanisms by which entinostat enhanced expression of MICA and MICB. Our data showed that entinostat increased the acetylation of histone 4 on the MICA and MICB gene promoters which enhanced MICA and MICB gene transcription. We also showed that entinostat decreased the expression of mir-20a, mir-93, and mir-106b, microRNAs that up-regulate both MICA and MICB. Although our findings showed that entinostat augmented NK cell-mediated cytotoxicity against OS cells in vitro, the in vivo studies failed to show enhanced efficacy of the combination therapy. This may be explained by our finding that while NK cells infiltrated into the lungs and were at the tumor periphery, we were unable to detect the presence of NK cells inside lung tumors. This suggests that adding a cytokine such as IL-2 and IL-21 may enhance the NK cells trafficking into the lung nodules and improve the NK cell therapy efficacy. Entinostat up-regulated the immune inhibitory molecule PD-L1 on OS cells. Therefore, blocking PD/PDL1 interaction by PD-L1 monoclonal antibody may increase the anti-tumor effect of entinostat+ NK cells. Further investigations are necessary to define the specific mechanism of resistance. Advisors/Committee Members: Eugenie S. Kleinerman, Joya Chandra, Dean Lee.

Subjects/Keywords: Osteosarcoma; NK cell; Entinostat; Life Sciences; Medicine and Health Sciences

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Kiany, S. (2017). EFFECT OF ENTINOSTAT ON NK CELL-MEDIATED CYTOTOXICITY AGAINST OS CELLS AND OS LUNG METASTSIS. (Doctoral Dissertation). Texas Medical Center. Retrieved from https://digitalcommons.library.tmc.edu/utgsbs_dissertations/733

Chicago Manual of Style (16^th Edition):

Kiany, Simin. “EFFECT OF ENTINOSTAT ON NK CELL-MEDIATED CYTOTOXICITY AGAINST OS CELLS AND OS LUNG METASTSIS.” 2017. Doctoral Dissertation, Texas Medical Center. Accessed February 26, 2021. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/733.

MLA Handbook (7^th Edition):

Kiany, Simin. “EFFECT OF ENTINOSTAT ON NK CELL-MEDIATED CYTOTOXICITY AGAINST OS CELLS AND OS LUNG METASTSIS.” 2017. Web. 26 Feb 2021.

Vancouver:

Kiany S. EFFECT OF ENTINOSTAT ON NK CELL-MEDIATED CYTOTOXICITY AGAINST OS CELLS AND OS LUNG METASTSIS. [Internet] [Doctoral dissertation]. Texas Medical Center; 2017. [cited 2021 Feb 26]. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/733.

Council of Science Editors:

Kiany S. EFFECT OF ENTINOSTAT ON NK CELL-MEDIATED CYTOTOXICITY AGAINST OS CELLS AND OS LUNG METASTSIS. [Doctoral Dissertation]. Texas Medical Center; 2017. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/733

Texas Medical Center

28. Philip, Kemly Mary. The Hypoxic Adenosine Response Modulates Macrophage Differentiation and Contributes to Lung Disease.

Degree: PhD, 2017, Texas Medical Center

URL: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/734

► Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease which affects 5 - 8 million individuals worldwide and 200,000 individuals in the United States… (more)

Subjects/Keywords: idiopathic pulmonary fibrosis; adenosine; alternatively-activated macrophages; hypoxia-inducible factor 1-alpha; acute lung injury; Medicine and Health Sciences

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Philip, K. M. (2017). The Hypoxic Adenosine Response Modulates Macrophage Differentiation and Contributes to Lung Disease. (Doctoral Dissertation). Texas Medical Center. Retrieved from https://digitalcommons.library.tmc.edu/utgsbs_dissertations/734

Chicago Manual of Style (16^th Edition):

Philip, Kemly Mary. “The Hypoxic Adenosine Response Modulates Macrophage Differentiation and Contributes to Lung Disease.” 2017. Doctoral Dissertation, Texas Medical Center. Accessed February 26, 2021. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/734.

MLA Handbook (7^th Edition):

Philip, Kemly Mary. “The Hypoxic Adenosine Response Modulates Macrophage Differentiation and Contributes to Lung Disease.” 2017. Web. 26 Feb 2021.

Vancouver:

Philip KM. The Hypoxic Adenosine Response Modulates Macrophage Differentiation and Contributes to Lung Disease. [Internet] [Doctoral dissertation]. Texas Medical Center; 2017. [cited 2021 Feb 26]. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/734.

Council of Science Editors:

Philip KM. The Hypoxic Adenosine Response Modulates Macrophage Differentiation and Contributes to Lung Disease. [Doctoral Dissertation]. Texas Medical Center; 2017. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/734

Texas Medical Center

29. Sun, Kaiqi. ROLE AND REGULATION OF SPHINGOSINE 1-PHOSPHATE IN ERYTHROCYTE.

Degree: PhD, 2017, Texas Medical Center

URL: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/736

► Sphingosine 1-phosphate (S1P) is a bioactive signaling sphingolipid produced in every mammalian cell. It plays a variety of important roles both in and outside… (more)

▼ Sphingosine 1-phosphate (S1P) is a bioactive signaling sphingolipid produced in every mammalian cell. It plays a variety of important roles both in and outside of cells. S1P is highly enriched in mature erythrocytes because of the high enzymatic activity of the S1P-generating enzyme Sphingosine Kinase 1 (Sphk1) and the absence of S1P degrading enzymes. Erythrocytes are considered only a major reservoir for S1P because they supply S1P to the circulation for the regulation of various physiological processes which include but are not limited to immune cell trafficking, endothelial integrity and hematopoietic stem cell mobilization. However, if S1P plays a role in the oxygen delivery ability of erythrocyte is unknown. Recent studies using unsupervised metabolomics screening revealed significantly higher S1P levels in Sickle Cell Disease mice. Moreover, the activity of erythrocyte Sphk1 was also higher in SCD and was further increased by hypoxia. Elevated erythrocyte Sphk1 and S1P contribute to sickling and SCD progression, though by an unknown mechanism. Here in this thesis, I provide answers to three key questions regarding S1P and Sphk1 in erythrocytes: i) the regulation of erythrocyte Sphk1 activation; ii) the function of erythrocyte Sphk1/S1P in hypoxia adaptation; iii) the mechanism underlying the detrimental role of erythrocyte Sphk1/S1P in SCD. Elevated adenosine, a signaling molecule induced by hypoxia, increases erythrocyte Sphk1 activity in normal and sickle erythrocytes by activating the A2B adenosine receptor (ADORA2B) which then leads to activation of protein kinase A (PKA) and Extracellular Signal Regulated Kinase 1/2 (ERK1/2) signaling pathways. Activated erythrocyte Sphk1 and elevated S1P are beneficial to hypoxia adaptation by promoting erythrocyte glycolysis to increase oxygen release. In SCD, erythrocyte Sphk1/S1P mediated elevation of glycolysis is detrimental because of the increased sickling and oxidative stress induced. The discoveries reported in this thesis not only extend human knowledge in understanding erythrocyte physiology and pathology, but also reveal several innovative mechanism-based therapeutic targets that can be harnessed to develop treatments for hypoxia and SCD. Advisors/Committee Members: Yang Xia, M.D, Ph.D., Yang Xia, M.D, Ph.D., Rodney E. Kellems, Ph.D..

Subjects/Keywords: Erythrocyte; Sphingosine 1-Phosphate; Sphingosine Kinase 1; Adenosine Signaling; Hypoxia Adaptation; Oxygen Release; Glucose Metabolism; Sickle Cell Disease; Biochemistry; Medicine and Health Sciences

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Sun, K. (2017). ROLE AND REGULATION OF SPHINGOSINE 1-PHOSPHATE IN ERYTHROCYTE. (Doctoral Dissertation). Texas Medical Center. Retrieved from https://digitalcommons.library.tmc.edu/utgsbs_dissertations/736

Chicago Manual of Style (16^th Edition):

Sun, Kaiqi. “ROLE AND REGULATION OF SPHINGOSINE 1-PHOSPHATE IN ERYTHROCYTE.” 2017. Doctoral Dissertation, Texas Medical Center. Accessed February 26, 2021. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/736.

MLA Handbook (7^th Edition):

Sun, Kaiqi. “ROLE AND REGULATION OF SPHINGOSINE 1-PHOSPHATE IN ERYTHROCYTE.” 2017. Web. 26 Feb 2021.

Vancouver:

Sun K. ROLE AND REGULATION OF SPHINGOSINE 1-PHOSPHATE IN ERYTHROCYTE. [Internet] [Doctoral dissertation]. Texas Medical Center; 2017. [cited 2021 Feb 26]. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/736.

Council of Science Editors:

Sun K. ROLE AND REGULATION OF SPHINGOSINE 1-PHOSPHATE IN ERYTHROCYTE. [Doctoral Dissertation]. Texas Medical Center; 2017. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/736

Texas Medical Center

30. Kwan, Suet Ying. Cyclin B1 mediates the effect of UCHL1 in promoting cell cycle progression in uterine papillary serous carcinoma.

Degree: PhD, 2017, Texas Medical Center

URL: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/737

► Uterine papillary serous carcinoma (UPSC) is an aggressive form of endometrial cancer with poor survival rates and a high risk of recurrence. The rarity… (more)

▼ Uterine papillary serous carcinoma (UPSC) is an aggressive form of endometrial cancer with poor survival rates and a high risk of recurrence. The rarity of UPSC poses challenges to the discovery of novel targeted therapies. Therefore, the purpose of this dissertation was to identify novel therapeutic targets that could aid in the management of UPSC. To do so, we began with the relatively large cohort of UPSC cases in the TCGA data set, which was used to identify differentially expressed genes between UPSC and low-grade endometrioid endometrial carcinoma (EEC) and normal tissue. We identified Ubiquitin Carboxyl-Terminal Hydrolase L1 (UCHL1) to be a gene of interest, as it was significantly upregulated in UPSC and correlated with poorer overall survival. These findings were validated through immunohistochemical analysis of an independent cohort of tumor samples. Due to its role as a deubiquitinating enzyme, we hypothesized that UCHL1 contributes to UPSC tumor progression by modulating the protein stability of target genes. To test this hypothesis, we first examined the functional role of UCHL1 in UPSC progression. Subsequently, we found that UCHL1 silencing reduced cell proliferation in vitro and in vivo. The treatment of UPSC-bearing mice with the UCHL1-specific inhibitor LDN-57444 via intraperitoneal injection also reduced tumor growth and increased overall survival times. Next, we found that the effect of UCHL1 on increased cell proliferation was due to its ability to stabilize cyclin B1 protein, an essential protein in mitotic progression. Specifically, we demonstrated that UCHL1 and cyclin B1 interact with each other in both the cytoplasm and nuclear space prior to mitosis. UCHL1 silencing increased the deubiquitination of cyclin B1, suggesting that UCHL1 counteracts the ubiquitination of cyclin B1 by the anaphase-promoting complex. Accordingly, UCHL1 silencing slowed the progression of cells into mitosis. Taken together, our findings indicate that UCHL1 impairs the degradation of cyclin B1, leading to uncontrolled cell cycle progression. In summary, we have identified UCHL1 as a prognostic marker for UPSC and a viable therapeutic target. Advisors/Committee Members: Karen H Lu, Russell R Broaddus, Wenliang Li.

Subjects/Keywords: Endometrial cancer; uterine papillary serous carcinoma; UCHL1; cyclin B1; Cancer Biology; Medicine and Health Sciences; Oncology; Translational Medical Research

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Kwan, S. Y. (2017). Cyclin B1 mediates the effect of UCHL1 in promoting cell cycle progression in uterine papillary serous carcinoma. (Doctoral Dissertation). Texas Medical Center. Retrieved from https://digitalcommons.library.tmc.edu/utgsbs_dissertations/737

Chicago Manual of Style (16^th Edition):

Kwan, Suet Ying. “Cyclin B1 mediates the effect of UCHL1 in promoting cell cycle progression in uterine papillary serous carcinoma.” 2017. Doctoral Dissertation, Texas Medical Center. Accessed February 26, 2021. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/737.

MLA Handbook (7^th Edition):

Kwan, Suet Ying. “Cyclin B1 mediates the effect of UCHL1 in promoting cell cycle progression in uterine papillary serous carcinoma.” 2017. Web. 26 Feb 2021.

Vancouver:

Kwan SY. Cyclin B1 mediates the effect of UCHL1 in promoting cell cycle progression in uterine papillary serous carcinoma. [Internet] [Doctoral dissertation]. Texas Medical Center; 2017. [cited 2021 Feb 26]. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/737.

Council of Science Editors:

Kwan SY. Cyclin B1 mediates the effect of UCHL1 in promoting cell cycle progression in uterine papillary serous carcinoma. [Doctoral Dissertation]. Texas Medical Center; 2017. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/737

		in
And / Or
		in
And / Or
		in
And / Or
		in

Open Access Theses and Dissertations