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Articles 3601 - 3630 of 7399

Full-Text Articles in Cell and Developmental Biology

Pyruvate Kinase Isoform M2 Influences Autophagy And Related Processes In Hepatocellular Carcinoma Cells, Matthew Lin May 2018

Pyruvate Kinase Isoform M2 Influences Autophagy And Related Processes In Hepatocellular Carcinoma Cells, Matthew Lin

University Scholar Projects

Hepatocellular carcinoma (HCC) is the most common form of liver cancer that affects ~14 million people in the world. Like all cancers, HCC is a disease that arises from unstinted cellular growth initiated by genetic alterations, metabolic changes, and dysregulation in key cellular pathways. Of interest is the relationship between metabolism and cell proliferation/degradation for therapeutic targeting. Pyruvate kinase M2 is a dimeric, glycolytically inactive isoform of the final enzyme involved in glycolysis, that is often upregulated in cancerous tissue. It is thought that the enzymatic function of PKM2 outside of glycolysis contributes to the biosynthesis of anabolic intermediates used …

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Investigation Of P-Glycoprotein (Pgp) Induction By Pgp Substrates To Induce Paclitaxel Resistance In Ovarian Cancer Cells, Ryker Penn May 2018

Investigation Of P-Glycoprotein (Pgp) Induction By Pgp Substrates To Induce Paclitaxel Resistance In Ovarian Cancer Cells, Ryker Penn

Theses & Dissertations

The purpose of this study was to investigate the development of chemotherapeutic resistance to paclitaxel in ovarian cancer cells after treatment with drugs that are substrates for P-glycoprotein (PGP). A core concept of this experiment was to identify if PGP substrate drugs could also act as PGP inducers after prolonged treatment in SKOV-3 ovarian cancer cells. In order to test this, SKOV-3 cells were exposed to either fexofenadine, a PGP substrate used as an antihistamine, or the chemotherapeutic drug vinblastine. After 42 days of drug treatment, ABCB1 gene expression was measured by qRT-PCR. Analysis of ABCB1 expression in treated cells …

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Functional Studies Of The E. Coli Proc And A Putative Ortholog Mrub_1345, Maureen Azar, Dr. Lori Scott May 2018

Functional Studies Of The E. Coli Proc And A Putative Ortholog Mrub_1345, Maureen Azar, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses the bioinformatics tools associated with the Guiding Education through Novel Investigation –Annotation Collaboration Toolkit (GENI-ACT) to predict gene function. We investigated the biological function of Escherichia coli and Meiothermus ruber proC genes using the complementation assay. In this research project, mutants of varying severity to the functional state of the protein were developed. The results showed that two or more amino acid deletions reduced or eliminated ProC function. Amino acid substitutions, on the other hand, were not severe enough to impact ProC function. Double and triple mutants …

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Effect Of Silk-Based Hydrogel Topography On Intestinal Epithelial Cell Morphology And Wound Healing In Vitro, Marisa E. Boch May 2018

Effect Of Silk-Based Hydrogel Topography On Intestinal Epithelial Cell Morphology And Wound Healing In Vitro, Marisa E. Boch

University Scholar Projects

Recent advances in the field of biomaterials have suggested that cells cultured on substrates resembling the native tissue mechanical properties, matrix and growth factor composition, and topography can adopt phenotypes that more closely resemble the in vivo tissue compared to cells cultured on non-mimetic constructs. Understanding the effect of culture substrate on in vitro tissue formation is important for bioengineering applications that include mechanistic studies of healthy tissue function and development of disease models. In this work, Caco-2 adenocarcinoma cells were seeded on flat and crypt-like topographies of 3D-printed cytocompatible hydrogels derived from silk fibroin protein. Silk hydrogels were selected …

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Circulating Tumor Cell Analysis In Preclinical Mouse Models Of Metastasis, Jenna Kitz, Lori E. Lowes, David Goodale, Alison L. Allan May 2018

Circulating Tumor Cell Analysis In Preclinical Mouse Models Of Metastasis, Jenna Kitz, Lori E. Lowes, David Goodale, Alison L. Allan

Anatomy and Cell Biology Publications

The majority of cancer deaths occur because of metastasis since current therapies are largely non-curative in the metastatic setting. The use of in vivo preclinical mouse models for assessing metastasis is, therefore, critical for developing effective new cancer biomarkers and therapies. Although a number of quantitative tools have been previously developed to study in vivo metastasis, the detection and quantification of rare metastatic events has remained challenging. This review will discuss the use of circulating tumor cell (CTC) analysis as an effective means of tracking and characterizing metastatic disease progression in preclinical mouse models of breast and prostate cancer and …

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Mice Harbouring An Oculodentodigital Dysplasia-Linked Cx43 G60s Mutation Have Severe Hearing Loss, Julia M. Abitbol, John J. Kelly, Kevin J. Barr, Brian L. Allman, Dale W. Laird May 2018

Mice Harbouring An Oculodentodigital Dysplasia-Linked Cx43 G60s Mutation Have Severe Hearing Loss, Julia M. Abitbol, John J. Kelly, Kevin J. Barr, Brian L. Allman, Dale W. Laird

Anatomy and Cell Biology Publications

Given the importance of connexin43 (Cx43, encoded by GJA1) function in the central nervous system and sensory organ processing, we proposed that it would also be crucial in auditory function. To that end, hearing was examined in two mouse models of oculodentodigital dysplasia that globally express GJA1 mutations resulting in mild or severe loss of Cx43 function. Although Cx43(I130T/+) mutant mice, with similar to 50% Cx43 channel function, did not have any hearing loss, Cx43(G60S/+) mutant mice, with similar to 20% Cx43 channel function, had severe hearing loss. There was no evidence of inner ear sensory hair cell loss, suggesting …

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Expression Of Androgen Receptor And Cancer Stem Cell Markers (Cd44 +/Cd24 - And Aldh1 +): Prognostic Implications In Invasive Breast Cancer, Nazia Riaz, Romana Idress, Sadia Habib, Iqbal Azam Syed, El Nasir Lalani May 2018

Expression Of Androgen Receptor And Cancer Stem Cell Markers (Cd44 +/Cd24 - And Aldh1 +): Prognostic Implications In Invasive Breast Cancer, Nazia Riaz, Romana Idress, Sadia Habib, Iqbal Azam Syed, El Nasir Lalani

Section of General Surgery

Background: Androgen receptor (AR) has emerged as a significant prognostic marker in early breast cancer (BCa). Association of AR with cancer stem cell (CSC) markers in BCa is unknown. Aim of the present study was to evaluate the immunohistochemical expression of AR, CD44, CD24 and ALDH1 in a cohort of Pakistani patients diagnosed with invasive BCa and to correlate the expression with 5- year disease free survival.
Patients and methods: We evaluated immunohistochemical expression AR, CD44, CD24 and ALDH1 in formalin fixed paraffin embedded archival blocks of 166 cases of primary invasive BCa (stage I-III) and correlated the expression with …

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Evolutionary Conservation Of Midline Repulsion By Robo Family Receptors In Flies And Mice, Allison Loy May 2018

Evolutionary Conservation Of Midline Repulsion By Robo Family Receptors In Flies And Mice, Allison Loy

Biological Sciences Undergraduate Honors Theses

As the nervous system develops in animal embryos, neuronal axons are guided to their synaptic targets by extra cellular cues that signal through axon guidance receptors expressed on the surface of the axon. In animals with bilateral symmetry, one of the important decisions made by nearly every axon in the embryonic nervous system is whether to stay on its own side of the body, or to cross the midline and connect to cells on the opposite side. The Roundabout (Robo) family is an evolutionarily conserved group of axon guidance receptors that regulate midline crossing in a wide range of animal …

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Cancer-Induced Muscle Wasting, Jacob Levi Brown May 2018

Cancer-Induced Muscle Wasting, Jacob Levi Brown

Graduate Theses and Dissertations

Cancer-induced muscle wasting, otherwise known as cancer-cachexia, is a wasting syndrome that occurs in approximately 80% of cancer patients that is the primary cause of death for 22%-30% of cancer cases. Cancer-cachexia may be metabolically induced; therefore, the central hypothesis of this dissertation is mitochondrial degeneration occurs before cancer-cachexia, and increased oxidative stress because of mitochondrial degeneration in muscle may instigate cancer-cachexia. Lewis Lung Carcinoma cells (LLC) or PBS (control) were injected into the hind-flank of C57Bl6/J mice at 8 wks age, and tumor allowed to develop for 1, 2, 3 or 4 wks. Mitochondrial quality, function, ROS emission, protein …

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Targeting Mitochondrial Proline Dehydrogenase (Prodh) With A Suicide Inhibitor As A Novel Anticancer Strategy, Beatrice Becker May 2018

Targeting Mitochondrial Proline Dehydrogenase (Prodh) With A Suicide Inhibitor As A Novel Anticancer Strategy, Beatrice Becker

Dissertations, Masters Theses, Capstones, and Culminating Projects

Proline dehydrogenase (PRODH) is a p53-inducible inner mitochondrial membrane protein linked to electron transport and capable of generating mitochondrial glutamate and intracellular ATP, especially under cellular stress conditions. Among a panel of 51 human breast cancer cell lines, PRODH and glutaminase (GLS1) expression levels were found to be inversely correlated (1) implicating two independent and alternative mitochondrial pathways supplying anaplerotic glutamate for cancer cell energy production and macromolecular synthesis. Proposing PRODH to be a promising cancer therapeutic target, we compared the in vitro cellular effects of PRODH knockdown by siRNA as well as competitive (L-tetrahydrofuroic acid, THFA; or 5-oxo-2-tetrahydrofurancarboxylic acid, …

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Identification Of Substrate-Selective Histone Deacetylases And Their Inhibitors That Mediate Her2 Transcript Stability, Mariah Alejo May 2018

Identification Of Substrate-Selective Histone Deacetylases And Their Inhibitors That Mediate Her2 Transcript Stability, Mariah Alejo

Dissertations, Masters Theses, Capstones, and Culminating Projects

Breast cancer is the most common malignancy diagnosed in women. 15-20% of these cancers overexpress the HER2 (ERRB2) oncoprotein. HER2-positive breast cancers are generally aggressive and are associated with poor prognosis. Unfortunately, only a mere 30% of HER2-positve patients respond to therapies when they are used as a single agent. Combining therapeutics can potentially lead to synergy and improved anticancer efficacy, and there is clearly a need for the development of new HER2-directed therapeutics. Newer approaches include the utilization of histone deacetylase (HDAC) inhibitors. It has been observed that HDAC inhibitors can induce the rapid decay of oncogenic transcripts such …

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Genetic Testing And A Real World Case Of Lynch Syndrome, Paige Montanaro May 2018

Genetic Testing And A Real World Case Of Lynch Syndrome, Paige Montanaro

Senior Honors Projects

In recent years, advancements in genetic testing methods have revolutionized the medical field by enhancing the ability to identify persons with an inherited predisposition to cancer. According to the American Society for Clinical Oncology, individuals should undergo genetic testing when he or she meets the following criteria: the individual demonstrates familial history that indicates a predisposition to certain cancers, the test can be adequately interpreted, and the results will aid in the diagnosis, treatment, or management of the patient or additional family members at risk. Genetic testing can be done on samples of hair, skin, blood, amniotic fluid, or other …

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Dicer1 Syndrome: Dicer1 Mutations In Rare Cancers, Jake C. Robertson, Cheryl L. Jorcyk, Julia Thom Oxford May 2018

Dicer1 Syndrome: Dicer1 Mutations In Rare Cancers, Jake C. Robertson, Cheryl L. Jorcyk, Julia Thom Oxford

Biology Faculty Publications and Presentations

DICER1 syndrome is a rare genetic disorder that predisposes individuals to multiple cancer types. Through mutations of the gene encoding the endoribonuclease, Dicer, DICER1 syndrome disrupts the biogenesis and processing of miRNAs with subsequent disruption in control of gene expression. Since the first description of DICER1 syndrome, case reports have documented novel germline mutations of the DICER1 gene in patients with cancers as well as second site mutations that alter the function of the Dicer protein expressed. Here, we present a review of mutations in the DICER1 gene, the respective protein sequence changes, and clinical manifestations of DICER1 syndrome. Directions …

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The Effects Of Insulin Signaling On Follicle Development And Activation, Ali Abdullah May 2018

The Effects Of Insulin Signaling On Follicle Development And Activation, Ali Abdullah

Renée Crown University Honors Thesis Projects - All

Women are born with the all the germ cells they will produce in their lifetime, with the establishment of this initial pool of germ cells being critical for fertility. In the mouse model, germ cells arrive at the genital ridge around 10.5 days post coitum (dpc) and divide by mitosis, forming cysts, until 13.5 dpc. These germ cells, referred to as oocytes, enter meiosis and begin to arrest in the diplotene stage of prophase I around 17.5 dpc. Simultaneously, the cysts begin to break apart and flattened granulosa cells surround the remaining single oocytes to form primordial follicles. Most oocytes …

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Wnt/Β-Catenin Signaling Components On Cancer Stem Cell Activation In Hepatocellular Carcinoma., Kevin Jacob May 2018

Wnt/Β-Catenin Signaling Components On Cancer Stem Cell Activation In Hepatocellular Carcinoma., Kevin Jacob

College of Arts & Sciences Senior Theses

Hepatocellular carcinoma is the most common type of liver cancer that, when diagnosed at advanced stage, has a 5-year survival rate of less than 12%. Alarmingly, the recurrence rate of HCC after curative and palliative treatment is 70% in the first 14 months. Cancer Stem Cells are a subpopulation in the tumor mass. Accumulating evidence suggests that the CSC subpopulation can initiate cancer and drives tumor recurrence, drug resistance, and metastasis. The Wnt/β-catenin pathway is a cardinal pathway contributing to stem-cell organogenesis during embryo development. The objective of the project was to identify canonical Wnt/β-catenin pathway components and/or downstream targets …

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Low Hemodynamic Loading Alters Heart Morphogensis In E8.5 To E9.5 Mouse Embryos, Tanner Gerard Hoog May 2018

Low Hemodynamic Loading Alters Heart Morphogensis In E8.5 To E9.5 Mouse Embryos, Tanner Gerard Hoog

Graduate Theses/Dissertations

Hemodynamic loading, the force exerted on the cardiovascular walls as blood circulates, has been shown to alter heart morphology in chick and zebrafish embryos, but has yet to be shown to singly influence mouse heart development. Defects of heart morphology found in model organisms with physically altered hemodynamics resemble the aberrations seen in human congenital heart disease and are therefore crucial to understand in a mammalian model. In the present study, hemodynamic loading was altered by lowering the hematocrit of early stage mouse embryos. This was accomplished by injecting acrylamide and TEMED into the blood islands of cultured embryos to …

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Investigation Of The Homologs Rad51 And Dmc1 Role In Cell Division And Homologous Recombination, Amaal Abulibdeh May 2018

Investigation Of The Homologs Rad51 And Dmc1 Role In Cell Division And Homologous Recombination, Amaal Abulibdeh

Graduate Theses/Dissertations

RecA-like proteins homologs Rad51 and Dmc1 (disruption of meiotic control) promote recombination between homologous chromosomes by repairing programmed DNA Double-Strand Breaks (DSBs). Dmc1 is a Recombinase involved in meiosis-specific repair of DSBs, whereas Rad51 has been found to be involved in meiotic and non-meiotic DSBs repair. Previous studies showed that when RAD51 is overexpressed, interhomologous recombination still occurs even when DMC1 is knocked out. Dmc1 and Rad51 have not been fully characterized in the ciliate Tetrahymena thermophila. In order to more fully investigate the role of Rad51 and Dmc1 in Homologous Recombination Repair (HHR), this work focuses on using …

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Ketone Bodies And Signaling In Pancreatic Cancer Cell Lines, Kyla B. Buettner, Pankaj K. Singh, Surendra K. Shukla May 2018

Ketone Bodies And Signaling In Pancreatic Cancer Cell Lines, Kyla B. Buettner, Pankaj K. Singh, Surendra K. Shukla

Theses/Capstones/Creative Projects

Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States, and 95% of these cases are caused by PDAC (pancreatic ductal adenocarcinoma). Ketone bodies have previously been shown to decrease cell proliferation and cancer-induced cachexia. The molecular mechanism of ketone body-mediated growth inhibition of pancreatic cancer cells is not well understood. Research conducted thus far has not explored which molecular pathways are affected by ketone body treatment in pancreatic cancer cells. In the current study, the effect of the ketone body sodium hydroxybutyrate on the JAK-STAT and mTOR pathways and cell migration was explored. A decrease …

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The Subcloning And Expression Of Munc18a In Escherichia Coli For Antibody Production And Analysis In Mast Cell Degranulation Reactions, Brandi Goble May 2018

The Subcloning And Expression Of Munc18a In Escherichia Coli For Antibody Production And Analysis In Mast Cell Degranulation Reactions, Brandi Goble

Honors Theses

Mast cells are secretory cells responsible for fighting off infection through the early recognition of pathogens. This process is completed through the secretion of proinflammatory mediators that are stored in secretory granules within the cytoplasm of the cell. The degranulation secretion process relies on regulated fusion of secretory granules to the cell membrane via membrane-bound SNARE proteins that bridges the two opposed membranes. The intricate regulation of SNARE-mediated mast cell degranulation is not well understood. However, Sec1/Munc18 (SM) proteins, specifically the Munc18 isoforms, are known to play a critical role in the process (Brochetta, et. al., 2014). The Xu lab …

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Mechanisms And Targeting Of Neurodevelopmental Regulator Rest In Medulloblastoma Dissemination, Keri Callegari May 2018

Mechanisms And Targeting Of Neurodevelopmental Regulator Rest In Medulloblastoma Dissemination, Keri Callegari

Dissertations and Theses (Open Access)

Molecular subgrouping of medulloblastoma (MB) has produced four subgroups: wingless (WNT), sonic hedgehog (SHH), group 3, and group 4. While patients with WNT tumors have the best prognosis, patients with SHH tumors have a more variable prognosis concurrent with metastatic disease. This subset of SHH patients have elevated levels of the neurogenic regulator, RE1 Silencing Transcription factor (REST). To understand the role of REST in MB, we utilized a novel transgenic mouse model wherein REST expression can be conditionally elevated during postnatal development in the cells of origin of SHH MB, cerebellar granule neural progenitors (GNPs). While these mice did …

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Investigating Invasion In Ductal Carcinoma In Situ With To Pographical Single Cell Genome Sequencing, Anna Casasent, Anna Casasent May 2018

Investigating Invasion In Ductal Carcinoma In Situ With To Pographical Single Cell Genome Sequencing, Anna Casasent, Anna Casasent

Dissertations and Theses (Open Access)

Synchronous Ductal Carcinoma in situ (DCIS-IDC) is an early stage breast cancer invasion in which it is possible to delineate genomic evolution during invasion because of the presence of both in situ and invasive regions within the same sample. While laser capture microdissection studies of DCIS-IDC examined the relationship between the paired in situ (DCIS) and invasive (IDC) regions, these studies were either confounded by bulk tissue or limited to a small set of genes or markers. To overcome these challenges, we developed Topographic Single Cell Sequencing (TSCS), which combines laser-catapulting with single cell DNA sequencing to measure genomic copy …

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Identifying New Genes Involved In Centromere Establishment, Megan Boyer May 2018

Identifying New Genes Involved In Centromere Establishment, Megan Boyer

Honors Scholar Theses

The centromere is a site on the chromosome that mediates accurate cell division by serving as a platform for kinetochore assembly, and microtubule attachment during cell division. Errors in the process of chromosome segregation can contribute to genetic irregularities, such as those seen in cancer and congenital defects. Our lab uses the ectopic centromere as a tool to discover what proteins may be involved in centromere establishment, defined as the deposition of CENP-A at the locus. We use the lacO/LacI system within Drosophila S2 cells that contain a CAL1-GFP- LacI transgene and an integrated lacO array to study the ectopic …

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Effects Of Piggybac Transposable Element Derived 5 (Pgbd5) In Cortical Tissue, Benjamin Shao May 2018

Effects Of Piggybac Transposable Element Derived 5 (Pgbd5) In Cortical Tissue, Benjamin Shao

Honors Scholar Theses

Many cancers are known to have genetic rearrangements, as these rearrangements develop abnormalities that can lead to certain types of cancer. Many of these genetic rearrangements can be caused by transposons, which are DNA sequences that can change its position and move to other positions within the genome. Transposons move to and integrate into a new location by the action of transposase enzymes, and recently genes that code for proteins similar to transposases and with transposase activity have been identified in the human and other vertebrate genomes. In this study, one of these genes, human piggyBac transposable element derived 5 …

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Effect Of Silk-Based Hydrogel Topography On Intestinal Epithelial Cell Morphology And Wound Healing In Vitro, Marisa E. Boch May 2018

Effect Of Silk-Based Hydrogel Topography On Intestinal Epithelial Cell Morphology And Wound Healing In Vitro, Marisa E. Boch

Honors Scholar Theses

Recent advances in the field of biomaterials have suggested that cells cultured on substrates resembling the native tissue mechanical properties, matrix and growth factor composition, and topography can adopt phenotypes that more closely resemble the in vivo tissue compared to cells cultured on non-mimetic constructs. Understanding the effect of culture substrate on in vitro tissue formation is important for bioengineering applications that include mechanistic studies of healthy tissue function and development of disease models. In this work, Caco-2 adenocarcinoma cells were seeded on flat and crypt-like topographies of 3D-printed cytocompatible hydrogels derived from silk fibroin protein. Silk hydrogels were selected …

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Regulation Of The Tubulin Homolog Ftsz In Escherichia Coli, Monika S. Buczek May 2018

Regulation Of The Tubulin Homolog Ftsz In Escherichia Coli, Monika S. Buczek

Dissertations, Theses, and Capstone Projects

Escherichia coli is a well-known pathogen, and importantly, a widely used model organism in all fields of biological sciences for cloning, protein purification, and as a model for Gram-negative bacterial species. And yet, researchers do not fully understand how this bacterium replicates and divides. Every year additional division proteins are discovered, which adds complexity to how we understand E. coli undergoes cell division. Due to their specific roles in cytokinesis, some of these proteins may be potential targets for development of antibacterials or bacteriostatics, which are much needed for fighting the current global antibacterial deficit. My thesis work focuses on …

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Development Of Endogenous Tagging Plasmids For Characterization Of Protein Interactions, Localization, And Post-Translational Modifications Of Tetrahymena Thermophila Rad23, Evan Andrew Wilson May 2018

Development Of Endogenous Tagging Plasmids For Characterization Of Protein Interactions, Localization, And Post-Translational Modifications Of Tetrahymena Thermophila Rad23, Evan Andrew Wilson

Graduate Theses/Dissertations

Rad23 is a protein involved in both nucleotide excision repair (NER) and proteasome-mediated degradation, and has been suggested to facilitate interactions between these two pathways. The model organism Tetrahymena thermophila, which has a transcriptionally silent micronucleus, provides a useful platform for studying the role of Rad23 in global genome NER (GG-NER). However, the ectopic expression systems used thus far in T. thermophila to study Rad23 are repressed by UV light and do not account for the background expression of endogenous RAD23; these phenomena prevent insightful gains to the true dynamics of Rad23. In this thesis, endogenous tagging …

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Functional Heterogeneity Of Fibroblasts In Dermal Wound Healing, Ehsan Ehsanipour May 2018

Functional Heterogeneity Of Fibroblasts In Dermal Wound Healing, Ehsan Ehsanipour

Dissertations and Theses (Open Access)

Impaired wound healing can lead to excessive scarring, dehiscence, chronic ulcers, and infection, which have adverse impact on the quality of life and pose a significant economic burden on the health care system. Thus, new therapeutic approaches are critically important. Dermal fibroblasts are critical players in cutaneous wound healing, possibly lending their contractile properties and extracellular matrix (ECM) remodeling functions to promote effective tissue repair. Dermal fibroblasts are also postulated to orchestrate tissue repair by interacting with and controlling other cell types in the wound microenvironment. It has become increasingly clear that the generic term “fibroblast” encompasses a diverse cell …

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Epithelial To Mesenchymal Transition As A Predictor Of Response To Polo-Like Kinase 1 Inhibition-Induced Apoptosis In Non-Small Cell Lung Carcinoma, Pavitra Viswanath May 2018

Epithelial To Mesenchymal Transition As A Predictor Of Response To Polo-Like Kinase 1 Inhibition-Induced Apoptosis In Non-Small Cell Lung Carcinoma, Pavitra Viswanath

Dissertations and Theses (Open Access)

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. Outcomes are poor for patients with recurrent, advanced or metastatic NSCLC. Polo-like kinase 1 (PLK1), involved in the regulation of mitotic processes and the response to DNA damage, is overexpressed in NSCLC. Inhibiting PLK1 may be an effective treatment for NSCLC patients as it is involved in the mechanisms of resistance to several chemotherapy drugs. PLK1 inhibition or knock-down has various effects in cancer cells, including mitotic arrest, apoptosis, and senescence. Predictive biomarkers have not been identified to select those patients who are likely to respond to …

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Trim24 In Normal & Malignant Hematopoiesis, Justin Shaw May 2018

Trim24 In Normal & Malignant Hematopoiesis, Justin Shaw

Dissertations and Theses (Open Access)

Treatment for acute myeloid leukemia (AML) has changed little in the past four decades. For the majority of AML patients, current treatment options include chemotherapy and allogeneic stem cell transplants, which also involves high-dose chemotherapy or radiation treatment. These options have little success in the long-run, as only an estimated 26% of patients survive five years post-diagnosis. In efforts to address this low survival rate, interest has increased for targeting epigenetic pathways in AML. This focus stems from the discovery that AML is frequently driven by blockades on hematopoietic stem cell differentiation, which involves a series of coordinated epigenetic changes. …

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Phosphorylation Impairs Dicer1 Function To Accelerate Aging And Tumorigenesis In Vivo, Neeraj Aryal May 2018

Phosphorylation Impairs Dicer1 Function To Accelerate Aging And Tumorigenesis In Vivo, Neeraj Aryal

Dissertations and Theses (Open Access)

Altered DICER1 protein levels are associated with developmental disorders, infertility, macular degenerative blindness, aging, and cancer in humans. Recently, post-translational regulation of Dicer1 via phosphorylation has been described in C. elegans. Oscillation of Dicer1 phosphorylation to regulate its activity is essential for germ cell development and embryogenesis in worms. These observations led us to posit that Dicer1 protein levels and activity are under tight regulation for normal mammalian homeostasis. To test whether phosphorylation of Dicer1 regulates its activity in mammals, I generated phospho-mimetic knock-in mouse models by replacing Serines 1712 and 1836 with Aspartic acids individually or together (dual …

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