Cell and Developmental Biology Commons^™

Regulation Of Morphogenesis In Filamentous Fungi, Haoyu Si

School of Biological Sciences: Dissertations, Theses, and Student Research

One of the distinguishing features of fungal cells is their highly polarized model of growth. Both yeast cells and hyphal cells grow by cell surface expansion at specified cortical sites. Although the same general mechanisms are likely to be involved in controlling the establishment of hyphal polarity in budding yeast and filamentous fungi, it is noticeable that hyphal cells are organized in a fundamentally different manner to yeast dells. For example, hyphal cells organize formins, septins and actins at the division site while simultaneously retain the same machinery at the tip; whereas yeast cells undergo a transient period of isotropic …

Regulation Of Dna Damage Processing By Covalent Modification Of Thymine Dna Glycosylase, Ryan D. Mohan

Electronic Thesis and Dissertation Repository

Thymine DNA glycosylase (TDG) is an essential DNA repair enzyme mediating excision of uracil and thymine mispaired with guanine within CpG contexts. Unrepaired, these lesions result in G:C to A:T transitions which are major contributors to genome instability. Interestingly, TDG interacts functionally with transcriptional regulators and participates in directed cytosine demethylation at promoters. TDG is subject to multiple post-translational modifications (PTM) and we undertook an analysis of how these regulate TDG function. Initially, we examined TDG regulation by small ubiquitin-like modifier (SUMO) and identified a novel SUMO binding motif (SBM1, residues 144-148). We hypothesized that SBM1, along with SBM2 (319-322), …

Characterization Of The Putative Xyloglucan Glycosyltransferase Gt14 In Arabidopsis Thaliana, Najam R. Syed

Honors Scholar Theses

Plant cell walls largely consist of matrix polysaccharides that are linked to cellulose microfibrils. Xyloglucan, the primary hemicellulose of the cell wall matrix, consists of a repeating glucose tetramer structure with xylose residues attached to the first three units ('XXXG'). In Arabidopsis thaliana, the core XXXG structure is further modified by enzymatic addition of galactose and fucose residues to the xylose side chains to produce XLXG, XXLG, XLLG and XLFG structures. GT14 is a putative glycosyltransferase in the GT47 gene family. Initial predictions of GT14's hydrophobic regions, based on its translated amino acid sequence, are almost identical to its Arabidopsis …

Alkylphenol Contamination In Homarus Americanus, Jennifer Renee Urban

Honors Scholar Theses

Alkylphenols are pollutants that are present in marine sediments and fishes. In earlier work it has been discovered that alkylphenols are present in the Homarus americanus, or the American lobster. Research suggests that alkylphenols could behave as endocrine disruptors as they have been found to affect juvenile hormone activity. It has been hypothesized that lobsters may be able to rid themselves of alkylphenol contamination through secreting these compounds into the environment or sequestering them in their tissues. In this study, I address the question of how lobsters may rid themselves of alkylphenols by analyzing hemolymph, muscle, gill, and shell samples …

Determination Of The Myogenic Potential Of Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells, Rory Coleman

Honors Scholar Theses

Human embryonic stem cells (hESCs) have the potential to

differentiate to all adult somatic cells. This property makes hESCs a very promising area of research for the treatment of disorders in which specific cell populations need to be restored. Despite this potential, research that focuses on producing mesodermally derived cell populations from hESCs is decidedly limited, notwithstanding the prevalence of disorders involving mesodermal tissues for which treatment options are limited. Skeletal muscle myoblasts are derivatives of mesodermal cells and are characterized by the expression of the MyoD gene. These cells are difficult to obtain from hESCs in a reproducible and …

Assessing The Phylogenetic Utility Of Dna Barcoding Using The New Zealand Cicada Genus Kikihia, Megan Ribak

Honors Scholar Theses

DNA Barcoding (Hebert et al. 2003) has the potential to revolutionize the process of identifying and cataloguing biodiversity; however, significant controversy surrounds some of the proposed applications. In the seven years since DNA barcoding was introduced, the Web of Science records more than 600 studies that have weighed the pros and cons of this procedure. Unfortunately, the scientific community has been unable to come to any consensus on what threshold to use to differentiate species or even whether the barcoding region provides enough information to serve as an accurate species identification tool. The purpose of my thesis is to analyze …

Macroh2a1 Regulation During The Cell Cycle Of Mouse Embryonic Stem Cells, Persis S. Thomas

Honors Scholar Theses

MacroH2A is a core histone variant that plays an important role in the X-inactivation process during differentiation of embryonic stem cells. It has been shown that macroH2A changes in localization during the cell cycle of somatic cells. This study aims to determine how macroH2A changes during the cell cycle of embryonic stem cells. Male and female mouse embryonic stem cells were transfected with a GFP::macroH2A construct and the relationship between macroH2A and the cell cycle was determined using FACS. This study shows that macroH2A is altered during the cell cycle of embryonic stem cells as it is in somatic cells …

Notch 1 Mediated Inhibition Of Nur77-Induced Apoptosis: Implications For T-Cell Leukemia, Jonathan George Rud

Open Access Dissertations

It is widely accepted that activating mutations of genes encoding the Notch family of transmembrane receptors, specifically Notch1, are associated with oncogenic transformation. Previous data from our lab has shown that an active form of Notch1 (NICD) provides protection against apoptosis in D011.10 T cells; and that this effect may be attributed to NICD binding the pro-apoptotic protein Nur77. Nur77 is an immediate early gene that is upregulated during both negative selection of thymocytes and activation-induced apoptosis in D011.10 T cells. Nur77 upregulation is tightly regulated and requires MEF2D, NFAT, and the transcriptional co-activator, p300, to effectively respond to apoptotic …

From Mouse Mammary Tumor Model To New Therapeutic Method ---Mammary Tumor Development In Balb/C-Trp53+/- Mice And Magnetic Nanoparticle Induced Heating For Cancer Treatment, Haoheng Yan

Open Access Dissertations

Mutation and loss of p53 function are common features among human breast cancers. We use BALB/c-Trp53+/- mice as a model to examine the sequence of events leading to mammary tumors. Mammary epithelium proliferation rates were similar in both BALB/c-Trp53+/- mice and wild type controls. Among the 28 mammary tumors collected from BALB/c-Trp53+/- mice, loss of heterozygosity for Trp53 was detected in more than 90% of invasive mammary tumors. Transplantation of Trp53+/- ductal hyperplasias indicated an association between loss of the wild type allele of Trp53 and progression to invasive carcinomas. Expression of biomarkers such as ERα, PR, Her2/Neu and activated …

Arabidopsis Thaliana Myosin Xi Is Necessary For Cell Fate Determination In Root Epidermis, Kevin Kuo

Chancellor’s Honors Program Projects

No abstract provided.

Delta Like Ligand 4 Is A Critical Regulator Of Bone Marrow Cell Differentiation Into Pericytes/Vascular Smooth Muscle Cells And Is Essential For The Vasculogenesis That Supports The Growth Of Ewing’S Sarcoma, Keri L. Stewart

Dissertations & Theses (Open Access)

We have previously shown that vasculogenesis, the process by which bone marrow-derived cells are recruited to the tumor and organized to form a blood vessel network de novo, is essential for the growth of Ewing’s sarcoma. We further demonstrated that these bone marrow cells differentiate into pericytes/vascular smooth muscle cells(vSMC) and contribute to the formation of the functional vascular network. The molecular mechanisms that control bone marrow cell differentiation into pericytes/vSMC in Ewing’s sarcoma are poorly understood. Here, we demonstrate that the Notch ligand Delta like ligand 4 (DLL4) plays a critical role in this process. DLL4 is essential for …

Functional Analysis Of Chromodomain Helicase Dna Binding Protein 2(Chd2) Mediated Genomic Stability, Sangeetha Rajagopalan

Doctoral Dissertations

Histone modifying enzymes and chromatin remodeling complexes play an important regulatory role in chromatin dynamics that dictate the interaction of regulatory factors involved in processes such as DNA replication, recombination, repair and transcription, with DNA template. The CHD (Chromodomain Helicase DNA Binding Protein) family of proteins is known to be involved in the regulation of gene expression, recombination and chromatin remodeling via their chromatin specific interactions and activities. Phenotypic analysis of the Chd2 mutant mouse model developed by our laboratory indicates that the Chd2 protein plays a critical role in tumor suppression as the heterozygous mutant mice develop spontaneous lymphomas. …

New Target Genes For Tumor Suppressors P53 And P73 In Regenerating Liver, Svitlana M. Kurinna

Dissertations & Theses (Open Access)

The p53-family of proteins regulates expression of target genes during tissue development and differentiation. Within the p53-family, p53 and p73 have hepatic-specific functions in development and tumor suppression. Despite a growing list of p53/p73 target genes, very few of these have been studied in vivo, and the knowledge regarding functions of p53 and p73 in normal tissues remains limited. p53+/-p73+/- mice develop hepatocellular carcinoma (HCC), whereas overexpression of p53 in human HCC leads to tumor regression. However, the mechanism of p53/p73 function in liver remains poorly characterized. Here, the model of mouse liver regeneration is used to identify new target …

Inhibition Of Deubiquitinase Activity And Ubiquitination Of Jak2 Blocks Cytokine Signaling And Induces Tumor Cell Apoptosis, Vaibhav Kapuria

Dissertations & Theses (Open Access)

The Jak-stat pathway is critical for cellular proliferation and is commonly found to be deregulated in many solid tumors as well as hematological malignancies. Such findings have spurred the development of novel therapeutic agents that specifically inhibit Jak2 kinase, thereby suppressing tumor cell growth. Tyrphostin AG490, the first described Jak2 inhibitor, displays poor pharmacology and requires high concentrations for anti-tumor activities. Our research group screened a small library of AG490 structural analogues and identified WP1130 as a potent inhibitor of Jak2 signaling. However, unlike AG490, WP1130 did not directly inhibit Jak2 kinase activity. Our results show that WP1130 induces rapid …

Cellular And Developmental Functions Of The Xenopus Arvcf-Catenin:Kazrin Complex, Kyucheol Cho

Dissertations & Theses (Open Access)

Xenopus ARVCF (xARVCF), a member of p120-catenin subfamily, binds cadherin cytoplasmic domains to enhance cadherin metabolic stability, or when dissociated, modulates Rho-family GTPases. We previously found that xARVCF binds directly to Xenopus KazrinA (xKazrinA), a widely expressed, conserved protein that bears little homology to established protein families. xKazrinA is also known to influence keratinocyte proliferation-differentiation and cytoskeletal activity. In my study, I first evaluated the expression pattern of endogenous Kazrin RNA and protein in Xenopus embryogenesis as well as in adult tissues. We then collaboratively predicted the helical structure of Kazrin’s coiled-coil domain, and I obtained evidence of Kazrin’s dimerization/oligomerization. …

Xenoestrogen-Specific Mechanisms Of Developmental Reprogramming Correlate With Gene Expression And Tumor Development, Kristen L. Greathouse

Dissertations & Theses (Open Access)

Environmental exposures during sensitive windows of development can reprogram normal physiological responses and alter disease susceptibility later in life in a process known as developmental reprogramming. We have shown that neonatal exposure to the xenoestrogen diethylstilbestrol (DES) can developmentally reprogram the reproductive tract in genetically susceptible Eker rats giving rise to complete penetrance of uterine leiomyoma. Based on this, we hypothesized that xenoestrogens, including genistein (GEN) and bisphenol A (BPA), reprogram estrogen-responsive gene expression in the myometrium and promote the development of uterine leiomyoma. We proposed the mechanism that is responsible for the developmental reprogramming of gene expression was through …

The Ubiquitin Ligase Ube4b Is Required For Efficient Epidermal Growth Factor Receptor Degradation, Natalie Sirisaengtaksin

Dissertations & Theses (Open Access)

The length of time that integral membrane proteins reside on the plasma membrane is regulated by endocytosis, a process that can inactivate these proteins by removing them from the membrane and may ultimately result in their degradation. Proteins are internalized and pass through multiple distinct intracellular compartments where targeting decisions determine their fate. Membrane proteins initially enter early endosomes, and subsequently late endosomes/multivesicular bodies (MVBs), before being degraded in the lysosome. The MVB is a subset of late endosomes characterized by the appearance of small vesicles in its luminal compartment. These vesicles contain cargo proteins sorted from the limiting membrane …

Discrete Fractional Calculus And Its Applications To Tumor Growth, Sevgi Sengul

Masters Theses & Specialist Projects

Almost every theory of mathematics has its discrete counterpart that makes it conceptually easier to understand and practically easier to use in the modeling process of real world problems. For instance, one can take the "difference" of any function, from 1st order up to the n-th order with discrete calculus. However, it is also possible to extend this theory by means of discrete fractional calculus and make n- any real number such that the ½-th order difference is well defined. This thesis is comprised of five chapters that demonstrate some basic definitions and properties of discrete fractional calculus …

The Consequences Of Disrupting The Mdm2-P53 Balance In Hematopoiesis, Hussein A. Abbas

Dissertations & Theses (Open Access)

The bone marrow accommodates hematopoietic stem cells and progenitors. These cells provide an indispensible resource for replenishing the blood constituents throughout an organism’s life. A tissue with such a high turn-over rate mandates intact cycling checkpoint and apoptotic pathways to avoid inappropriate cell proliferation and ultimately the development of leukemias. p53, a major tumor suppressor, is a transcription factor that regulates cell cycle, and induces apoptosis and senescence. Mice inheriting a hypomorphic p53 allele in the absence of Mdm2, a p53 inhibitor, have elevated p53 cell cycle activity and die by postnatal day 13 due to hematopoietic failure. Hematopoiesis progresses …

Cip4 And Src In Promoting The Migration And Invasion Of Breast Cancers, Christina S. Pichot

Dissertations & Theses (Open Access)

Cellular invasion represents a critical early step in the metastatic cascade, and many proteins have been identified as part of an “invasive signature.” The non-receptor tyrosine kinase Src is commonly upregulated in breast cancers, often in conjunction with overexpression of EGFR. Signaling from this pathway stimulates cell proliferation, migration, and invasion and frequently involves proteins that regulate the cytoskeleton. My data demonstrates that inhibition of Src, using the small-molecule inhibitor dasatinib, impairs cellular migration and invasion. Furthermore, Src inhibition sensitizes the cells to the effects of the chemotherapeutic doxorubicin resulting in dramatic, synergistic inhibition of proliferation with combination treatments. The …