Cell and Developmental Biology Commons^™

Fancm And Faap24 Maintain Genomic Stability Through Cooperative And Unique Functions, Yucai Wang

Dissertations & Theses (Open Access)

Fanconi anemia (FA) is a rare recessive genetic disease with an array of clinical manifestations including multiple congenital abnormalities, progressive bone marrow failure and profound cancer susceptibility. A hallmark of cells derived from FA patients is hypersensitivity to DNA interstrand crosslinking agents such as mitomycin C (MMC) and cisplatin, suggesting that FA- and FA-associated proteins play important roles in protecting cells from DNA interstrand crosslink (ICL) damage. Two genes involved in the FA pathway, FANCM and FAAP24, are of particular interest because they contain DNA interacting domains. However, there are no definitive patient mutations for these two genes, and the …

Tet1: A Unique Dna Demethylase For Maintenance Of Dna Methylation Pattern, Chunlei Jin

Dissertations & Theses (Open Access)

DNA methylation at the C5 position of cytosine (5-methylcytosine, 5mC) is a crucial epigenetic modification of the genome and has been implicated in numerous cellular processes in mammals, including embryonic development, transcription, X chromosome inactivation, genomic imprinting and chromatin structure. Like histone modifications, DNA methylation is also dynamic and reversible. However, in contrast to well defined DNA methyltransferases, the enzymes responsible for erasing DNA methylation still remain to be studied. The ten-eleven translocation family proteins (TET1/2/3) were recently identified as Fe(II)/2-oxoglutarate (2OG)-dependent 5mC dioxygenases, which consecutively convert 5mC into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine and 5-carboxylcytosine both in vitro and in mammalian …

Genetic Analysis Of The Hippo Pathway In Mouse Liver, Li Lu

Dissertations & Theses (Open Access)

Cancer therapy and tumor treatment remain unsolved puzzles. Genetic screening for tumor suppressor genes in Drosophila revealed the Hippo-signaling pathway as a kinase cascade consisting of five core components. Disrupting the pathway by deleting the main component genes breaks the balance of cell proliferation and apoptosis and results in epithelial tissue tumorigenesis. The pathway is therefore believed to be a tumor suppressor pathway. However, a corresponding role in mammals is yet to be determined. Our lab began to investigate the tumor suppression function of the potent mammalian Hippo pathway by putting floxed alleles into the mouse genome flanking the functional-domain-expressing …

The Effects Of Cytokinin On The Transcriptional Regulation Of Pin Expression In Arabidopsis Thaliana, Elizabeth Burgess

Honors Theses and Capstones

The processes of cell division and differentiation are critical to the development of any multicellular organism. During the formation of plant roots these processes take place at a region of the root tip called the meristem. Cytokinin and auxin are two plant growth hormones that influence this process. Although these two growth hormones are both necessary they also appear in many ways to have an antagonistic relationship. As meristematic root cells undergo differentiation they cease dividing. It has been proposed that the size of the root meristem and thus the overall rate of root growth are determined by the balance …

Uncovering Dual Roles For Perk Signaling During Experimentally Induced Pancreatitis, Elena Fazio

Electronic Thesis and Dissertation Repository

Pancreatitis is characterized by inappropriate activation of digestive enzyme

precursors, or zymogens, local and systemic inflammation, dysregulation of

cellular calcium (Ca2+), and induction of the unfolded protein response (UPR).

The UPR consists of three distinct pathways all of which are activated during

pancreatitis. However, the molecular roles of each remain unclear. The

protein kinase RNA (PKR)-like ER kinase (PERK) pathway reduces general

protein translation by phosphorylating eIF2!, and is activated within minutes

of initiating pancreatic damage. Microarray analysis carried out by our lab

revealed robust upregulation of the PERK pathways members Activating

Transcription Factor (ATF) 3 and stanniocalcin (STC) 2. …

Studies On Enzyme Functional Evolution In The Sabath Multigene Family Using Phylogenetic And Biochemical Approaches, Ruiqi Huang

Masters Theses

Gene duplication is believed to be the major source for providing genetic materials for the innovation and diversification of protein functions; natural selection and/or neutral drift then works on these genetic materials to guide their evolutionary directions. Here, I used the salicylic acid/benzoic acid/theobromine (SABATH) multigene family to study how natural selection acted on duplicated genes to prompt functional diversification. Members in this family methylate plant secondary metabolites by transferring the methyl group from S-adenosyl-L-methionine (SAM) to the carboxyl group or ring nitrogen of the substrates. In the Apocynaceae and Solanaceae lineage of this family, I documented three putative gene …

The Dietary Isoprenoid Perillyl Alcohol Inhibits Telomerase Activity In Prostate Cancer Cells, Tabetha Sundin

Theses and Dissertations in Biomedical Sciences

This is the first evidence that a plant-derived compound–perillyl alcohol regulates telomerase activity via the mammalian target of rapamycin (mTOR) pathway in prostate cancer cells. Telomerase–the enzyme responsible for immortalizing cells through telomeric repeats addition–is de-repressed early in an aspiring cancer cell. We hypothesized that perillyl alcohol regulates hTERT (human telomerase reverse transcriptase) at the translational and post-translational levels via its effects on the mTOR pathway. A rapid suppression of telomerase activity was detected in prostate cancer cell lines (PC-3 and DU145) in response to biologically-relevant concentrations and short incubations of perillyl alcohol or the mTOR inhibitor—rapamycin.

Western blot analysis …

Identification Of Cellular Functions Of Cardiolipin As Physiological Modifiers Of Barth Syndrome, Amit Shridhar Joshi

Wayne State University Dissertations

Cardiolipin (CL) is an anionic phospholipid synthesized in the mitochondrial inner membrane. Perturbation of CL metabolism leads to Barth syndrome (BTHS), a life threatening genetic disorder. I utilized genetic, biochemical and cell biological approaches in yeast to elucidate the cellular functions of CL. Understanding the functions of CL is expected to shed light on the pathology and possible treatments for BTHS.

BTHS is caused by mutations in TAZ1, which encodes a CL remodeling enzyme called tafazzin. BTHS patients exhibit a wide range of clinical presentations, indicating that physiological modifiers influence the BTHS phenotype. A targeted synthetic lethality screen was performed …

Comparative Developmental Transcriptomics Of Echinoderms, Roy Vaughn

USF Tampa Graduate Theses and Dissertations

The gastrula stage represents the point in development at which the three primary germ layers diverge. At this point the gene regulatory networks that specify the germ layers are established and the genes that define the differentiated states of the tissues have begun to be activated. These networks have been well characterized in sea urchins, but not in other echinoderms. Embryos of the brittle star Ophiocoma wendtii share a number of developmental features with sea urchin embryos, including the ingression of mesenchyme cells that give rise to an embryonic skeleton. Notable differences are that no micromeres are formed during cleavage …