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Theses/Dissertations

2014

Cell Biology

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Full-Text Articles in Molecular Biology

The Role Of Nag-1 In Tumorigenesis, Kyung-Won Min Dec 2014

The Role Of Nag-1 In Tumorigenesis, Kyung-Won Min

Doctoral Dissertations

This dissertation explores the nature of a divergent member of the Transforming Growth Factor-β [beta] superfamily, the non-steroidal anti-inflammatory drugs activated gene (NAG-1), as it relates to its regulation and biological activity in cancer context. Our lab has extensively studied on the molecular mechanism by which phytochemicals and NSAIDs induce apoptosis correlation with NAG-1 expression in human colorectal cancer (CRC) cells. Significant data from in vitro studies suggest that NAG-1 has an anti-tumorigenic activity which elicits apoptosis in a cyclooxygenase (COX)-independent manner in CRC cells. Indeed, NAG-1 transgenic mice developed less aberrant polyp foci (APC) compared to those of ...


Novel Posttranslational Modification In Lkb1 Activation And Function, Szu-Wei Lee Dec 2014

Novel Posttranslational Modification In Lkb1 Activation And Function, Szu-Wei Lee

UT GSBS Dissertations and Theses (Open Access)

Cancer cells display dramatic alterations in cellular metabolism to meet their needs of increased growth and proliferation. In the last decade, cancer research has brought these pathways into focus, and one emerging issue that has come to attention is that many oncogenes and tumor-suppressors are intimately linked to metabolic regulation (Jones and Thompson, 2009). One of the key tumor-suppressors involved in metabolism is Liver Kinase B1 (LKB1). LKB1 is the major upstream kinase of the evolutionarily conserved metabolic sensor—AMP-activated protein kinase (AMPK). Activation of the LKB1/AMPK pathway provides a survival advantage for cells under energy stress. LKB1 forms ...


Investigation Of Nuclear And Cytoplasmic Functions Of The Dlipin Protein Of Drosophila Melanogaster, Qiuyu Chen Dec 2014

Investigation Of Nuclear And Cytoplasmic Functions Of The Dlipin Protein Of Drosophila Melanogaster, Qiuyu Chen

Theses and Dissertations

Lipin family proteins are highly conserved proteins present in species ranging from mammals to yeast. Lipin 1, the first Lipin gene identified in fatty liver dystrophy (fld) mutant mice, encodes the bifunctional protein Lipin 1, which can serve as an Mg2+-dependent phosphatidic acid phosphatase (PAP) and transcriptional co-regulator. dLipin, the single Lipin ortholog of Drosophila melanogaster, is required in triglyceride synthesis and fat body development. To study the transcriptional co-regulator activity of dLipin, nuclear receptors were screened to find receptors that interact with dLipin. The genetic interaction data indicated that Drosophila hepatic nuclear receptor 4 (HNF4) was a promising ...


Regulation Of Cdk1 Activity During The G1/S Transition In S. Cerevisiae Through Specific Cyclin-Substrate Docking: A Dissertation, Samyabrata Bhaduri Oct 2014

Regulation Of Cdk1 Activity During The G1/S Transition In S. Cerevisiae Through Specific Cyclin-Substrate Docking: A Dissertation, Samyabrata Bhaduri

GSBS Dissertations and Theses

Several cell cycle events require specific forms of the cyclin-CDK complexes. It has been known for some time that cyclins not only contribute by activating the CDK but also by choosing substrates and/or specifying the location of the CDK holoenzyme. There are several examples of B-type cyclins identifying certain peptide motifs in their specific substrates through a conserved region in their structure. Such interactions were not known for the G1 class of cyclins, which are instrumental in helping the cell decide whether or not to commit to a new cell cycle, a function that is non-redundant with B-type cylins ...


Associated Behavioral, Genetic, And Gene Expression Variation With Alternative Life History Tactics In Salmonid Fishes, Ashley Chin-Baarstad Oct 2014

Associated Behavioral, Genetic, And Gene Expression Variation With Alternative Life History Tactics In Salmonid Fishes, Ashley Chin-Baarstad

Open Access Dissertations

Individual differences in behavior can have potential fitness consequences and often reflect underlying genetic variation. My research focuses on three objectives related to individual level variation: 1) evaluating the innate behavioral variation within and between individuals, families, and progeny of different life-history types across time; 2) testing for differences in gene expression within the brain associated with this behavioral variation; and 3) using genetic polymorphisms to test for associations with ecotype, as well as population structure, in polymorphic populations. First, we evaluated the variation in a suite of ecologically relevant behaviors across time in juvenile progeny produced from crosses within ...


Small Rnas And Argonautes Provide A Paternal Epigenetic Memory Of Germline Gene Expression To Promote Thermotolerant Male Fertility: A Dissertation, Colin C. Conine Sep 2014

Small Rnas And Argonautes Provide A Paternal Epigenetic Memory Of Germline Gene Expression To Promote Thermotolerant Male Fertility: A Dissertation, Colin C. Conine

GSBS Dissertations and Theses

During each life cycle, gametes must preserve and pass on both genetic and epigenetic information, making the germline both immortal and totipotent. In the male germline the dramatic morphological transformation of a germ cell through meiosis, into a sperm competent for fertilization, while retaining this information is an incredible example of cellular differentiation. This process of spermatogenesis is inherently thermosensitive in numerous metazoa ranging from worms to man. Here, I describe the role of two redundant AGO-class paralogs, ALG-3/4, and their small RNA cofactors, in promoting thermotolerant male fertility in Caenorhabditis elegans. alg-3/4 double mutants exhibit temperature dependent ...


Role And Regulation Of Snon/Skil And Plscr1 Located At 3q26.2 And 3q23, Respectively, In Ovarian Cancer Pathophysiology, Madhav Karthik Kodigepalli Sep 2014

Role And Regulation Of Snon/Skil And Plscr1 Located At 3q26.2 And 3q23, Respectively, In Ovarian Cancer Pathophysiology, Madhav Karthik Kodigepalli

Graduate Theses and Dissertations

Ovarian cancer is one of the most common causes of gynecological cancer related deaths in women. In 2014, the estimated number of deaths due to ovarian cancer is 14,270 with occurrence of over 22, 240 new cases (National Cancer Institute, http://seer.cancer.gov/statfacts/html/ovary.html). Despite improvement in treatment strategies, the 5-year survival rate is still below 50% mainly due to chemoresistance and relapse. Amplification of chromosomal region 3q26 is a common characteristic in various epithelial cancers including ovarian cancer. This region harbors various oncogenes including the TGFβ signaling mediators EVI1 and SnoN/SkiL, PKCι and ...


Transcriptional Regulation Of Sinorhizobium Meliloti Cell Cycle-Related Genes In The Δcbra Mutant And Root Nodules Of Medicago Sativa, Corey S. Hazekamp Aug 2014

Transcriptional Regulation Of Sinorhizobium Meliloti Cell Cycle-Related Genes In The Δcbra Mutant And Root Nodules Of Medicago Sativa, Corey S. Hazekamp

Graduate Masters Theses

Sinorhizobium meliloti is a Gram-negative alphaproteobacterium and nitrogen-fixing symbiont, which undergoes a novel cell cycle modification during its' host-microbe interaction. I intend to monitor the transcriptional regulation of cell cycle-related genes during free-loving growth, in addition to monitoring their expression during symbiosis. Using genes known to be regulated by CtrA in C. crescentus or predicted to be regulated by CtrA in S. meliloti, I aim to show how certain cell cycle genes are regulated in S. meliloti. In C. crescentus, CtrA acts as a transcription factor that is active when phosphorylated and inactive when not phosphorylated. In S. meliloti, CbrA ...


Elucidating The Signalling Pathway Of Mer Tyrosine Kinase Receptor In Efferocytosis, Ekenedelichukwu Azu Aug 2014

Elucidating The Signalling Pathway Of Mer Tyrosine Kinase Receptor In Efferocytosis, Ekenedelichukwu Azu

Electronic Thesis and Dissertation Repository

Efferocytosis is the clearance of apoptotic cells and is necessary for homeostasis. Mer Tyrosine Kinase (MerTK) is a crucial efferocytic receptor whose loss is associated with chronic inflammatory diseases and autoimmunity. While previous studies have shown that MerTK mediates efferocytosis through a unique mechanism that requires integrins, MerTK signalling pathway remains unknown. Given this unusual internalization mechanism, I hypothesized that MerTK signals and engages integrins through a novel signalling pathway different from that used by other phagocytic receptors. Therefore, this study aimed to identify the signalling pathways activated by MerTK, utilizing conventional cell biology and pharmacological approaches.

I found that ...


Development Of Peripheral Innervation In The Frog Xenopus Laevis, Mitali A. Gandhi Aug 2014

Development Of Peripheral Innervation In The Frog Xenopus Laevis, Mitali A. Gandhi

Theses and Dissertations

The skin in Xenopus laevis is innervated by two different sets of mechanosensory neurons at different times during development. Rohon Beard (RB) neurons start differentiating during gastrulation, innervate the embryonic skin and mediate sensory function during hatching. Dorsal Root Ganglion (DRG) neurons start differentiating after neural crest migration, innervate adult epidermal targets and mediate mechanosensory function during larval and adult stages and eventually replace RB neurons. The change in sensory neurons occurs during the transformation of skin, sensory structures, and behavior from their embryonic to their larval forms. We hypothesized that developmental changes in either the sensory end organs or ...


Roles For B-Raf Kinase In The Specific Regulation Of Α4Β1 Integrin In T Cells, Wells S. Brown Aug 2014

Roles For B-Raf Kinase In The Specific Regulation Of Α4Β1 Integrin In T Cells, Wells S. Brown

UT GSBS Dissertations and Theses (Open Access)

The regulation of integrin-mediated adhesion is of vital importance to adaptive and innate immunity. Integrins are versatile proteins and mediate T cell migration and trafficking by binding to ECM or other cells, as well as initiating intracellular signaling cascades promoting survival or activation. The mitogen activated-protein kinase (MAPK) pathway is known to be downstream from integrins and regulate survival, differentiation, and motility. However, secondary roles for canonical MAPK pathway members are being discovered. We show chemical inhibition of RAF by Sorafenib or shRNA-mediated knockdown of B-Raf reduces T cell resistance to shear stress to α4β1 integrin ligands vascular cell adhesion ...


Egfr Modulates Microrna Maturation In Response To Hypoxia Through Phosphorylation Of Argonaute2, Jia Shen Aug 2014

Egfr Modulates Microrna Maturation In Response To Hypoxia Through Phosphorylation Of Argonaute2, Jia Shen

UT GSBS Dissertations and Theses (Open Access)

MicroRNAs (miRNAs) are generated by two-step processing to yield small RNAs that negatively regulate target gene expression at posttranscriptional level. Deregulation of miRNAs has been linked to diverse pathological processes, including cancer. Recent studies have also implicated miRNAs in regulatory roles to cope with a spectrum of stresses, such as hypoxia, which is frequently encountered in the poorly angiogenic core of a solid tumor. However, the upstream regulators of miRNA biogenesis machineries remain obscure, raising the question of how tumor cells efficiently coordinate and impose specificity on miRNA expression and function in response to stresses. Here, we show that EGFR ...


Energy Stress Causes Chaperones To Assemble Into Cytoplasmic Complexes, Kimberly J. Cope Aug 2014

Energy Stress Causes Chaperones To Assemble Into Cytoplasmic Complexes, Kimberly J. Cope

UT GSBS Dissertations and Theses (Open Access)

The majority of proteins require molecular chaperones to assist their folding into tertiary and quaternary structures. Certain stresses can compromise the weak hydrophobic forces responsible for these structures and lead to protein unfolding, misfolding, and aggregation. Aggregates of proteins are hallmarks of devastating diseases such as Alzheimer’s, Parkinson’s, and Huntington’s diseases. Fortunately, bacteria, plants, and fungi have a potent disaggregase, named Hsp104 in Saccharomyces cerevisiae. Recently, heat-induced aggregates, termed Q-bodies, were found to contain three molecular chaperones: Hsp70, Hsp104, and Hsp42. Their coalescence from small puncta into larger inclusions required Hsp104. During glucose deprivation, a stress that ...


Antiviral Responses In Mouse Embryonic Stem Cells: Differential Development Of Cellular Mechanisms In Type I Interferon Production And Response, Ruoxing Wang Aug 2014

Antiviral Responses In Mouse Embryonic Stem Cells: Differential Development Of Cellular Mechanisms In Type I Interferon Production And Response, Ruoxing Wang

Dissertations

Embryonic stem cells (ESCs) have been recognized as a promising cell source for regenerative medicine. Intensive research over the past decade has led to the possibility that ESC-derived cells will be used for the treatment of human diseases. However, increasing evidence indicates that ESC-derived cells generated by the current differentiation methods are not fully functional. It is recently recognized that ESC-derived cells lack innate immunity to a wide range of infectious agents and inflammatory cytokines. When used in patients, ESC-derived cells would be placed in wounded sites that are exposed to various pathogens and inflammatory cytokines; therefore, their viability and ...


Key Residues Of Human Cytoplasmic Protein Tyrosine Phosphatase-A And -B For Substrate Binding And Specificity, Byunghyun Park Jul 2014

Key Residues Of Human Cytoplasmic Protein Tyrosine Phosphatase-A And -B For Substrate Binding And Specificity, Byunghyun Park

Open Access Theses

Reversible tyrosine phosphorylation plays an important role in signaling pathways that are essential for regulating cellular growth, differentiation and metabolism. Moreover, several human diseases such as diabetes, obesity and cancers are associated with the deregulation of protein tyrosine phosphatases (PTPs). Several studies provide evidence that PTPs not only contribute to cellular differentiation, but over-expression of these molecules also leads to transformation of non-transfomed cells as well. Based on these results, designing specific PTP inhibitors may ultimately function as potential therapeutic agents to treat various diseases including cancer, diabetes, and autoimmune diseases. EphA2 is a receptor tyrosine kinase which is hypo-phosphorylated ...


Functional Analysis Of Cytosolic Hsp70 Nucleotide Exchange Factor Networks In Yeast, Jennifer Lynn Abrams May 2014

Functional Analysis Of Cytosolic Hsp70 Nucleotide Exchange Factor Networks In Yeast, Jennifer Lynn Abrams

UT GSBS Dissertations and Theses (Open Access)

The Hsp70 class of molecular chaperones play critical roles in protein homeostasis via an ATP-dependent folding cycle. Cytosolic Hsp70s in the budding yeast Saccharomyces cerevisiae, Ssa and Ssb, interact with up to three distinct nucleotide exchange factors (NEFs) homologous to human counterparts; Sse1/Sse2/HSP110, Fes1/HspBP1, and Snl1/Bag1. In an effort to understand the differential functional contributions of the cytosolic NEFs to protein homeostasis (“proteostasis”), I carried out comparative genetic, biochemical and cell biological analyses. For these studies, I developed protocols to monitor protein disaggregation and reactivation in a near real-time coupled assay that revealed the importance of ...


Characterization Of Ftsa-Ftsn Interaction During Escherichia Coli Cell Division, Kimberly.Busiek@Gmail.Com K. Busiek May 2014

Characterization Of Ftsa-Ftsn Interaction During Escherichia Coli Cell Division, Kimberly.Busiek@Gmail.Com K. Busiek

UT GSBS Dissertations and Theses (Open Access)

Division of a bacterial cell into two equal daughter cells requires precise assembly and constriction of the division machinery, or divisome. The Escherichia coli divisome includes nearly a dozen essential cell division proteins that assemble at midcell between segregating sister chromosomes. FtsZ, a homolog of eukaryotic tubulin, is the first essential cell division protein to localize at midcell where it polymerizes into a ring-shaped scaffold (Z ring). Establishment of the Z ring is required for recruitment of downstream cell division proteins including FtsA, a cytoplasmic protein that tethers the Z ring to the inner membrane. Following localization of FtsA and ...


Neurotrophins And Their Effects On Breast Cancer Cell Proliferation And Migration, Kayla Elise Minser Apr 2014

Neurotrophins And Their Effects On Breast Cancer Cell Proliferation And Migration, Kayla Elise Minser

Open Access Theses

Cancer is a large health issue in all parts of the world. In the United States alone, approximately 1 in 4 deaths are cancer related. Breast cancer is a particularly prevalent form, accounting for a little over 14 percent of all cancer incidence. The largest obstacle to overcome for breast cancer morbidity is metastasis. Over 90 percent of all breast cancer related deaths are due to metastasis. Because metastasis is a complex, multi-step process, it is difficult to treat. A recent observation in the Kirshner lab has revealed a type of phenotypic plasticity, where migratory cancer cells have a neuronal-like ...


Exploration Of Mutations In Erythroid 5-Aminolevulinate Synthase That Lead To Increased Porphyrin Synthesis, Erica Jean Fratz Mar 2014

Exploration Of Mutations In Erythroid 5-Aminolevulinate Synthase That Lead To Increased Porphyrin Synthesis, Erica Jean Fratz

Graduate Theses and Dissertations

5-Aminolevulinate synthase (ALAS; EC 2.3.1.37) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that catalyzes the first committed step of heme biosynthesis in animals, the condensation of glycine and succinyl-CoA yielding 5-aminolevuliante (ALA), CoA, and CO2. Murine erythroid-specific ALAS (mALAS2) variants that cause high levels of PPIX accumulation provide a new means of targeted, and potentially enhanced, photosensitization. Transfection of HeLa cells with expression plasmids for mALAS2 variants, specifically for those with mutated mitochondrial presequences and a mutation in the active site loop, caused significant cellular accumulation of PPIX, particularly in the membrane. Light treatment of HeLa ...


Molecular Landscape Of Induced Reprogramming: A Dissertation, Chao-Shun Yang Feb 2014

Molecular Landscape Of Induced Reprogramming: A Dissertation, Chao-Shun Yang

GSBS Dissertations and Theses

Recent breakthroughs in creating induced pluripotent stem cells (iPS cells) provide alternative means to obtain embryonic stem (ES) cell-like cells without destroying embryos by introducing four reprogramming factors (Oct3/4, Sox2, and Klf4/c-Myc or Nanog/Lin28) into somatic cells. However, the molecular basis of reprogramming is largely unknown. To address this question, we employed microRNAs, small molecules, and conducted genome-wide RNAi screen, to investigate the regulatory mechanisms of reprogramming.

First we showed that depleting miR-21 and miR-29a enhances reprogramming in mouse embryonic fibroblasts (MEFs). We also showed that p53 and ERK1/2 pathways are regulated by miR-21 and miR-29a ...


Immature Myeloid Cells Promote Tumor Formation Via Non-Suppressive Mechanism, Myrna Lillian Ortiz Feb 2014

Immature Myeloid Cells Promote Tumor Formation Via Non-Suppressive Mechanism, Myrna Lillian Ortiz

Graduate Theses and Dissertations

ABSTRACT

Although there is ample evidence linking chronic inflammation with cancer, the cellular mechanisms involved in early events leading to tumor development remain unclear. Myeloid cells are an intricate part of inflammation. They consist of mature cells represented by macrophages, dendritic cells and granulocytes and a population of Immature Myeloid Cells (IMC), which in healthy individuals are cells in transition to mature cells. There is a substantial expansion of IMC in cancer and many other pathological conditions which is associated with pathologic activation of these cells. As a result, these cells acquire the ability to suppress immune responses and are ...


Polymerase Alpha Components Associate With Telomeres To Mediate Overhang Processing, Raffaella Diotti Feb 2014

Polymerase Alpha Components Associate With Telomeres To Mediate Overhang Processing, Raffaella Diotti

All Dissertations, Theses, and Capstone Projects

Telomeres consist of TTAGGG repeats, which end with a 3' G-overhang and are bound by a six-protein complex, known as Shelterin. In humans, telomeres shorten at each cell division, unless telomerase is expressed and able to add telomeric repeats to the 3' G-overhang. However, for effective telomere maintenance, the DNA strand complementary to that made by telomerase must be synthesized. In this study, I focused on the Polα/primase complex, in particular the subunits p68 (POLA2, the regulatory subunit) and p180 (Polα, the catalytic subunit), and their potential roles at telomeres. I was able to detect p180, p68 and OBFC1 ...


The Sex Of The Cell Dictates Its Response, Carlos Ganesh Penaloza Feb 2014

The Sex Of The Cell Dictates Its Response, Carlos Ganesh Penaloza

All Dissertations, Theses, and Capstone Projects

Male and female differences in frequency of occurrence in disease have perplexed scientists for some time. This in part derives from limitations in the systems in which one can evaluate sex differences. At the organismal level, differences can be hidden by a myriad of extensive and complex factors. Additional limitations exist since most biomedical studies are performed almost exclusively on male subjects, as the female hormonal milieu is intrinsically more variable and too troublesome for routine inclusion in research protocols. Research documenting sex differences continues to grow, and while most researchers suggests that sex hormones are at the core of ...


Role Of Cytoskeletal Remodeling In T Cell Receptor Signaling And Integrin Activation At The Immunological Synapse, Alexander Babich Jan 2014

Role Of Cytoskeletal Remodeling In T Cell Receptor Signaling And Integrin Activation At The Immunological Synapse, Alexander Babich

Publicly Accessible Penn Dissertations

The efficiency of an immune response critically depends on the ability of T cells to respond to antigens. Upon encountering cognate antigenic peptides on the surface of antigen-presenting cells, T cells form a specialized interface, termed the immunological synapse (IS), which serves as the site of information transfer between the cells. This contact zone is characterized by the enrichment of signaling receptors, kinases and adaptor proteins, and is the site of extensive cytoskeletal remodeling. The versatile nature and spatio-temporal regulation of signaling cascades at the IS has long been recognized but the exact mechanisms that coordinate these processes remain poorly ...


Chromatin Compaction And Genome Reorganization During Spermatogenesis In M. Musculus And Sporulation In S. Cerevisiae, Jessica Michelle Bryant Jan 2014

Chromatin Compaction And Genome Reorganization During Spermatogenesis In M. Musculus And Sporulation In S. Cerevisiae, Jessica Michelle Bryant

Publicly Accessible Penn Dissertations

Gametogenesis is a complex process that results in a highly differentiated gamete capable of transmitting genetic and epigenetic information to the next generation. In the cases of mammalian spermatogenesis and yeast sporulation, an extreme post-meiotic compaction of the genome is key to gamete function. While genome compaction in sperm is reliant upon a histone-to-protamine transition, yeast spores accomplish compaction with a full complement of histones. Although the mechanisms behind such striking chromatin dynamics are largely unknown, several histone variants and post-translational modifications, especially acetylation of histone H4, have been implicated in these processes. The following studies elucidate the roles of ...


Dynamics And Fate Of The Inner Membrane Complex In Apicomplexan Parasites, Dinkorma Toure Ouologuem Jan 2014

Dynamics And Fate Of The Inner Membrane Complex In Apicomplexan Parasites, Dinkorma Toure Ouologuem

Publicly Accessible Penn Dissertations

The eukaryotic phylum apicomplexa encompasses many thousands of parasite species of medical and veterinary importance, including Plasmodium sp. and Toxoplasma gondii. These obligate intracellular parasites survive and replicate within suitable eukaryotic hosts, ultimately rupturing infected cells to release parasites that can invade neighboring cells. Repeated cycles of infection and lysis are responsible for the pathogenesis associated with these parasites. Apicomplexan parasites replicate using an unusual process known as endodyogeny or schizogony, in which daughters are constructed de novo within the mother. This distinctive mode of replication relies on dynamic assembly of an organelle known as the Inner Membrane Complex (IMC ...


Cellular Interactions During Motor Nerve Regeneration, Allison F. Rosenberg Jan 2014

Cellular Interactions During Motor Nerve Regeneration, Allison F. Rosenberg

Publicly Accessible Penn Dissertations

Vertebrate peripheral nerves can regenerate, enabling severed axons to reconnect with their original synaptic targets. The interactions between injured nerves with cells in their environment, as well as the functional significance of these interactions, have not been determined in vivo and in real time. Here we provide the first minute-by-minute account of cellular interactions between laser transected motor nerves, macrophages, and Schwann cells in live intact zebrafish using transgenic lines that label each cell type in vivo. We find that axon fragmentation triggers macrophage invasion into the nerve to engulf axonal debris, and that delaying nerve fragmentation in a Wlds ...


Degradation Of The Oncoprotein Mdmx In Neurodegenerative States: Evidence For A Pro-Survival Role Of Mdmx In Neurons, Daniel James Colacurcio Jan 2014

Degradation Of The Oncoprotein Mdmx In Neurodegenerative States: Evidence For A Pro-Survival Role Of Mdmx In Neurons, Daniel James Colacurcio

Publicly Accessible Penn Dissertations

Neurodegenerative diseases, such as Alzheimer Disease (AD) and HIV–associated neurocognitive disorder (HAND) represent a tremendous burden to healthcare and a devastating impact on society. A common feature of neurodegenerative diseases is progressive dysfunction and death of neurons in key regions of the brain. Observations of dysregulated cell cycle proteins in the brains of patients, along with research in animal models and cultured cells, suggest that aberrant functions of cell cycle proteins contribute to neuronal death and progression of neurodegenerative diseases.

The p53 tumor suppressor is a key component in cell cycle signaling and cell death. p53 maintains multiple functions ...


Epigenetic Regulation Of Progenitor Cell Commitment By Hdac3, Mudit Gupta Jan 2014

Epigenetic Regulation Of Progenitor Cell Commitment By Hdac3, Mudit Gupta

Publicly Accessible Penn Dissertations

Tissue-specific progenitor cells emerge during development to expand and differentiate into the multiple cell lineages that populate the embryo. Appropriate differentiation of these precursor cells requires coordinated expression of numerous lineage-specific genes and repression of alternative fate programs. Epigenetic regulators are enzymes capable of activating or silencing large genomic domains by altering histone modifications, DNA methylation status and chromatin organization. Although differentiating progenitor cells undergo epigenetic changes and epigenetic factors are required for appropriate cell behavior, the precise mechanism of how these proteins influence cell fate remains unclear. In this dissertation, I examine the role of histone deacetylase 3 in ...


Distinct Patterns Of Ccr5 Versus Alternative Coreceptor Dependence In Non-Natural Host Versus Natural Host Simmian Immunodeficiency Virus Infection, Sarah Tc Elliott Jan 2014

Distinct Patterns Of Ccr5 Versus Alternative Coreceptor Dependence In Non-Natural Host Versus Natural Host Simmian Immunodeficiency Virus Infection, Sarah Tc Elliott

Publicly Accessible Penn Dissertations

Natural host sooty mangabeys infected with simian immunodeficiency viruses (SIV) exhibit high plasma viral loads without widespread CD4+ T cell loss. By contrast, non-natural host rhesus macaques experimentally infected with related SIV exhibit high viral loads but display subsequent CD4+ T cell loss and progression to AIDS, analogous to the effects of HIV-1 infection in humans. Several mechanisms have been proposed to explain these discrepant outcomes, including infection of distinct target cells in vivo. Cell targeting is substantially determined at the level of viral entry. Prior work demonstrated that sooty mangabey infection occurs in the absence of functional coreceptor CCR5 ...