Open Access. Powered by Scholars. Published by Universities.®
- Keyword
-
- Breast cancer (3)
- CD44 (2)
- PU.1 (2)
- ACL (1)
- ATP citrate lyase (1)
-
- Acetyl-CoA (1)
- Active DNA demethylation (1)
- Acute Respiratory Distress Syndrome (1)
- Aldehyde dehydrogenase (ALDH) (1)
- Antigen presenting cell (1)
- B cell development (1)
- B cells (1)
- Biomarker (1)
- Blastocyst (1)
- Blood pressure (1)
- Bone tissue (1)
- CRISPR-Cas9 (1)
- Cancer (1)
- Cancer immunotherapy (1)
- Cancer stem cell (CSC) (1)
- Cell Signalling (1)
- Cell biology (1)
- Cell cycle (1)
- Cell fate (1)
- Cellular MRI (1)
- ChIP-sequencing (1)
- Chondrocytes (1)
- Chronic kidney disease (1)
- Coiled coils (1)
- Connexin43 (1)
Articles 1 - 18 of 18
Full-Text Articles in Entire DC Network
The Mitochondrial Calcium Uniporter Regulator 1 (Mcur1) Matrix Domain Is A Self-Associated Multimer Sensitive To Divalent Cations, Naveed Siddiqui
The Mitochondrial Calcium Uniporter Regulator 1 (Mcur1) Matrix Domain Is A Self-Associated Multimer Sensitive To Divalent Cations, Naveed Siddiqui
Electronic Thesis and Dissertation Repository
Mitochondria are primarily appreciated for the generation of adenosine triphosphate (ATP), a chemical store of energy required by all cells. These organelles, however, also play key roles in apoptosis, autophagy and shaping cytosolic calcium (Ca2+) signaling via Ca2+ uptake into the mitochondrial matrix. This Ca2+ uptake is mediated chiefly via the mitochondrial Ca2+ uniporter (MCU), an inner mitochondrial membrane protein that oligomerizes to form a Ca2+ selective pore. MCU is regulated by several protein binding partners, including the recently identified MCU regulator-1 (MCUR1). MCUR1 stabilizes a higher order MCU heterocomplex through interactions with MCU …
19f-Mri To Monitor Therapeutic Cell Migration And Distribution, Corby Fink
19f-Mri To Monitor Therapeutic Cell Migration And Distribution, Corby Fink
Electronic Thesis and Dissertation Repository
A major hurdle hindering the advancement of cell-based cancer vaccines is the inability to non-invasively track in vivo therapeutic cell migration. Within cancer immunotherapy, antigen presenting cell-based (APC) immunotherapies can be dendritic cell-based (DC) and elicit de novo anti-tumor immune responses or formulated as mixed APC-based immunotherapy generated from peripheral blood mononuclear cells (PBMC). Mixed APC-based therapies contain monocytes and B cells as APC and can enhance a pre-existing anti-tumor immune response such that objective anti-tumor responses are observed. In either APC-based formulation, the quantity of anti-tumor APC reaching a secondary lymphoid organ post injection is predictive of the magnitude …
Determining The Molecular Mechanisms Of Pacs-1-Mediated Protein Sorting, Brennan S. Dirk
Determining The Molecular Mechanisms Of Pacs-1-Mediated Protein Sorting, Brennan S. Dirk
Electronic Thesis and Dissertation Repository
Membrane trafficking events are required to direct proteins to their precise subcellular locations. The cellular Phosphofurin Acidic Cluster Sorting protein – 1 (PACS-1) has emerged as a protein of interest in controlling the localization of a multitude of cellular and viral proteins. Specifically, PACS-1 is hijacked by type-1 Human Immunodeficiency Virus (HIV-1) to contribute to immune evasion in addition to regulating neuroendocrine hormone storage and release. To accomplish this, PACS-1 connects the cytoplasmic tail of cellular receptors to the heterotetrameric adaptor proteins (APs) to form a functional trafficking unit. Throughout this dissertation, I explored the role of PACS-1 and AP-1 …
The Role Of Hand1 In The Development Of The Lateral Plate Mesoderm In Xenopus, Victoria A. Deveau
The Role Of Hand1 In The Development Of The Lateral Plate Mesoderm In Xenopus, Victoria A. Deveau
Electronic Thesis and Dissertation Repository
The transcription factor hand1 is expressed in the heart, lateral plate mesoderm (LPM) and neural crest cells during development. As Hand1-null mice die early in embryogenesis, identification of the precise role of Hand1 in development is difficult. In Xenopus, we observed that hand1 expression patterns correlates very closely with development of LPM derivatives, leading us to hypothesize that hand1 is required for normal LPM development. Using hand1 knockdown and overexpression models in Xenopus, development of LPM derivatives were assessed by whole mount in situ hybridization. I found that hand1 is required for proper heart morphogenesis. Furthermore, hand1 …
Effects Of Maternal Protein Restriction On The Pulmonary Surfactant System During The Early Life And Adulthood, Reza Khazaee
Effects Of Maternal Protein Restriction On The Pulmonary Surfactant System During The Early Life And Adulthood, Reza Khazaee
Electronic Thesis and Dissertation Repository
Fetal growth restriction (FGR) is defined by low birth weight and contributes to a variety of adult-onset diseases with different severities between males and females. However, the effects of FGR on the pulmonary surfactant are not fully elucidated. In this thesis, first, we investigated the FGR effects on the lung function and the surfactant system at the early postnatal life. It was hypothesized that FGR contributes to alterations of lung mechanics and the surfactant system during the neonatal period. Second, we assessed the FGR effects on the surfactant system in response to sepsis in adulthood. It was hypothesized that FGR …
Lung-Derived Selectins Interact With Cd44 And Enhance The Migration Of Breast Cancer Cells, Sami U. Khan
Lung-Derived Selectins Interact With Cd44 And Enhance The Migration Of Breast Cancer Cells, Sami U. Khan
Electronic Thesis and Dissertation Repository
The lung is among the deadliest sites of breast cancer metastasis. Previous work from our laboratory demonstrated that aggressive CD44-expressing breast cancer cells preferentially metastasize to the lung in vivo, and observed the presence of multiple CD44-interacting proteins in the lung including E-, L- and P-selectin. We hypothesized that lung-derived selectins promote breast cancer migration and/or growth via interactions with CD44. Using an ex vivo model of the soluble lung-microenvironment, we demonstrate that lung-derived selectins enhance in vitro migration but not proliferation of breast cancer cells. Co-immunoprecipitation experiments reveal that CD44 expressed by breast cancer cells in vitro interacts …
Examining The Tissue-Level And Gross Phenotypic Effects Of The Connexin43i130t/+ Mutation On The Developing Mouse Skull, Sommer G.E. Jarvis
Examining The Tissue-Level And Gross Phenotypic Effects Of The Connexin43i130t/+ Mutation On The Developing Mouse Skull, Sommer G.E. Jarvis
Electronic Thesis and Dissertation Repository
The purpose of this study was to investigate the effects of reduced Connexin43 function on the developing skull phenotype, osteoblast and chondrocyte proliferation and differentiation, and to determine if a correlation exists between cell processes and gross morphology. Using the Cx43I130T/+mouse model, skull shape was analyzed using geometric morphometrics and cell proliferation and differentiation were assessed using immunohistochemistry at late embryonic and early post-natal stages. The largest shape changes between Cx43I130T/+ and wildtype mice were observed in the cranial base and facial skeleton. Changes infacial morphology correspond to reduced osteoblast differentiation. However, no changes in chondrocyte proliferation …
The Characterization Of Cx31 In Keratinocytes And Its Link To Erythrokeratodermia Variabilis Et Progressiva, Akina Au
Electronic Thesis and Dissertation Repository
The connexin 31 (Cx31) mutants L135V and L209F are linked to the skin disease erythrokeratodermia variabilis et progressiva. We investigated the life-cycle of Cx31 and its interplay with co-expressed Cx26, Cx30 and Cx43 in rat epidermal keratinocytes. We demonstrated that the apparent half-life of Cx31 was extended compared to Cx43, and that Cx31 gap junctions persisted longer at the cell surface. In REKs, Cx31 gap junctions were dynamic and the ablation of Cx43 did not prevent Cx31 gap junction formation. Furthermore, Cx31 and Cx30 localized to the same gap junctions and exhibited the highest correlation coefficient. Lastly, we demonstrated that …
Characterizing The Cognitive And Emotional Effects Of Delta-9-Tetrahydrocannabinol In Distinct Hippocampal Sub-Regions, Dinat Khan
Electronic Thesis and Dissertation Repository
The objective of this study is to determine the potential differential effects of THC in the DH or VH sub-regions, as well as the upstream effects on PFC neuronal activity and oscillations. Rodents used for electrophysiology were infused with THC or vehicle in the DH or VH regions, combined with PFC recordings. Additionally, a battery of behavioural paradigms was performed. Deficits in short-term memory when THC was infused into both regions was observed, however working memory was impaired with VH infusions only. This could be due to THC-induced dysregulation in the PFC, as beta oscillations were significantly decreased selectively in …
Elucidation Of The Signaling Pathway Of Mertk, Kyle Taruc
Elucidation Of The Signaling Pathway Of Mertk, Kyle Taruc
Electronic Thesis and Dissertation Repository
Mer tyrosine kinase (MERTK) is a receptor tyrosine kinase which mediates efferocytosis-the recognition and uptake of apoptotic cells. MERTK serves as the predominant efferocytic receptor in several tissues, including in the heart, with single nucleotide polymorphisms associated with up to a 75% increased risk of atherosclerosis in humans. MERTK facilitates the internalization of apoptotic cells via a MERTK/integrin pathway that involves, in part, PI-3-kinase signaling and signaling via Src-family kinases. While these elements of the MERTK signaling pathway have been identified, much of MERTK’s signaling mechanisms remain to be elucidated. Pharmacological inhibitors were used to block signaling through canonical phagocytic …
The Role Of Spi-B And Pu.1 Transcription Factors In B Cell Development And In Suppression Of Leukemogenesis, Carolina Reyes Batista
The Role Of Spi-B And Pu.1 Transcription Factors In B Cell Development And In Suppression Of Leukemogenesis, Carolina Reyes Batista
Electronic Thesis and Dissertation Repository
The E26 transformation-specific transcription factors PU.1 and Spi-B are required for B cell maturation within the bone marrow. PU.1 expression is first detected in hematopoietic stem and progenitor cells, whereas Spi-B levels arise as early as the pro-B cell stage. The expression levels of both factors are maintained as B cells progress in development, and the lack of PU.1 and Spi-B at early stages impairs B cell development and can lead to B-cell leukemia. We hypothesized that PU.1 and Spi-B control events associated with the transition from high to low proliferative stages in B cell development and the absence of …
The Role Of Pu.1 In Lipid Metabolism And Cell Cycle Regulation In Myeloid Progenitor Cells, Jess Rhee
The Role Of Pu.1 In Lipid Metabolism And Cell Cycle Regulation In Myeloid Progenitor Cells, Jess Rhee
Electronic Thesis and Dissertation Repository
PU.1 is a transcription factor essential for myeloid development. High PU.1 levels promote cell cycle arrest and differentiation. Low levels promote proliferation and have been associated with leukemia. BN mice are homozygous for a hypomorphic allele of Spi1 that results in expression of PU.1 at 20% of normal levels. Induction of PU.1 expression in BN myeloid progenitor cells causes cell cycle arrest, differentiation, and the upregulation of microRNAs targeting lipid metabolic genes. Acly encoding ATP citrate lyase (ACL) was one of these targets. ACL produces acetyl-CoA which is essential for fatty acid synthesis. We hypothesized that inhibiting ACL would cause …
Proteomic Characterization Of Ovarian And Breast Cancer Microenvironments For Improved Diagnostics And Therapeutic Targeting, Dylan Z. Dieters-Castator
Proteomic Characterization Of Ovarian And Breast Cancer Microenvironments For Improved Diagnostics And Therapeutic Targeting, Dylan Z. Dieters-Castator
Electronic Thesis and Dissertation Repository
Cancers exist within complex microenvironments formed by heterogeneous cell types. This diversity creates significant challenges for detection, diagnosis and treatment. Mass spectrometry-based proteomics is a powerful approach capable of characterizing complex biological systems which are characteristic of cancer biology. In this thesis, proteomics was utilized to answer several questions related to ovarian cancer diagnosis and detection, and the effects of NODAL, an embryonic morphogen, on the breast cancer secretome and stromal cell recruitment. First, I compared multiple sample preparation techniques and found high-pH/low-pH fractionation to yield the greatest proteome coverage over commonly used approaches. Second, I compared the proteomes from …
The Role Of P66shc In Mouse Blastocyst Development, Nicole A. Edwards
The Role Of P66shc In Mouse Blastocyst Development, Nicole A. Edwards
Electronic Thesis and Dissertation Repository
The earliest cell fate specification events during mammalian development occur in the blastocyst-stage preimplantation embryo, during which a pluripotent cell population is established. These cells form the basis of the developing fetus and must be correctly specified in order for successful development to occur. Cell signalling in response to environmental cues has a critical role in cell differentiation. The signalling adaptor protein p66Shc is expressed in mammalian embryos and promotes apoptosis and permanent embryo arrest in response to stress-inducing conditions. However, loss-of-function studies suggest that p66Shc may be important for embryonic development to the blastocyst stage. In this thesis, I …
The Role Of Thymine-Dna Glycosylase In Transcriptional Regulation, Bart Kolendowski
The Role Of Thymine-Dna Glycosylase In Transcriptional Regulation, Bart Kolendowski
Electronic Thesis and Dissertation Repository
Precise control over transcriptional regulation is required for normal cell function. Errors in transcriptional regulation underpin many diseases including cancer. Thymine DNA Glycosylase (TDG) is a base excision repair protein and a coregulator that has been implicated in a diverse set of fundamental biological processes including embryonic development, nuclear receptor signaling and Wnt signaling. Importantly, TDG has been shown to play an important role in transcriptional regulation in a wide variety of systems. Details surrounding the mechanism through which TDG acts remain unclear. In this thesis we explore the role of TDG in Estrogen Receptor (ER)-dependent signaling and in cellular …
Functional Changes Associated With Shroom3 Deficiency And Mutation: Implications In Renal Pathophysiology And Disease, Doyun Ko
Electronic Thesis and Dissertation Repository
Chronic kidney disease (CKD) is a substantial global health burden that has recently been linked to the genetic locus SHROOM3 by several genome-wide association studies. Shroom3 is an actin-binding protein that is necessary for inducing apical constriction in epithelial cells. Our lab has previously shown that Shroom3 is critical for proper kidney development and loss of Shroom3 produces symptoms associated with CKD. As hypertension is both a leading cause and comorbidity of CKD, I hypothesized that loss of Shroom3 confers increased susceptibility to hypertension. Using a high-salt induced model of hypertension, I show that Shroom3 deficient mice do not become …
Characterizing The Role Of Thymine Dna Glycosylase In Transcriptional Regulation And Cancer In Vivo, Mohammad Haider Hassan
Characterizing The Role Of Thymine Dna Glycosylase In Transcriptional Regulation And Cancer In Vivo, Mohammad Haider Hassan
Electronic Thesis and Dissertation Repository
Cytosine methylation (5mC) is essential for transcriptional control and genomic stability and is often used as a prognostic marker in cancer. Although 5mC has long been considered a relatively stable epigenetic mark, recent studies have demonstrated that it can be reversed enzymatically by TET proteins which oxidize 5mC into 5-hydroxymethylcytosine (5-hmC), and then to 5-formylcytosine (5-fC) and 5-carboxylcytosine (5caC). This mechanism is known as active DNA demethylation and the base excision repair enzyme Thymine DNA Glycosylase (TDG) plays an essential role in this process by removing 5-fC and 5-caC which are subsequently replaced by the unmethylated cytosine. Importantly, homozygous loss …
Influence Of The Metastatic Microenvironment On Stem-Like Human Breast Cancer Cells, Ashkan Sadri
Influence Of The Metastatic Microenvironment On Stem-Like Human Breast Cancer Cells, Ashkan Sadri
Electronic Thesis and Dissertation Repository
Ninety percent of breast cancer-related mortalities result from metastasis. We have previously demonstrated that stem-like ALDHhiCD44+ breast cancer cells are critical for metastasis, and preferentially target the lung and bone marrow (BM). We hypothesize organ tropism occurs through promotion of the ALDHhiCD44+ phenotype. Using a 2D ex vivo model, lung and BM conditioned media (CM) were utilized to assess their influence on stem-like phenotype and behavior. Exposure of human breast cancer cells to lung-CM significantly decreased the proportion of cells with a stem-like ALDHhiCD44+ phenotype, decreased expression of cancer stem cell (CSC)-related genes, and increased gene expression related to migration …