Molecular Biology Commons^™

Specificity And Catalytic Mechanism Of Dna Glycosylases In Udg Superfamily, Bo Xia

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DNA can be damaged by several kinds of endogenous and exogenous reactive nitrogen species. Under nitosative stress, uracil (U), hypoxanthine (I), xanthine (X) and oxanine (O) are four major deaminated DNA bases derived from cytosine (C), adenine (A) and guanine (G) respectively. To repair this type of DNA damage, several different repair pathways are involved.

My dissertation work mainly focused on the uracil-DNA glycosylase (UDG) superfamily, which includes several groups of enzymes that recognize the damaged DNA bases and initiate the base excision repair (BER) pathway, one of the most important repair pathways to deal with deaminated DNA bases. Chapter …

Prolactin And Isplatin Combination Treatment Inhibit Tumorspheres Formation And Tumor Growth In Mice, Eric Hingleung Lee

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Cancer stem cells (CSCs) are defined as a small population of tumor initiating cells that are responsible for the initiation, development, progression, and recurrence of cancer. The chemo and radiation resistance of CSCs remains one of the major obstacles in conventional anti-cancer therapies. One of the reasons that conventional chemotherapeutics are not effective in targeting CSCs is that CSCs are usually in a non-proliferative or dormant state. In this perspective, targeting CSCs by inducing its proliferation and differentiation and simultaneously applying chemotherapeutics may be an alternative approach. The current study investigates the effect of prolactin (PRL), a hormone intimately involved …

Biochemical Investigation Into Initiation Of Fatty Acid Synthesis In The African Trypanosomes, Sunayan Ray

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My doctoral studies focused on studying FA metabolism in the deadly protozoan parasite T. brucei. In my dissertation, I will be addressing various aspects of the regulation of TbACC, which catalyzes the first committed step in FA synthesis. In the second chapter, I hypothesized that TbACC is regulated in response to environmental lipids. I examined changes in TbACC RNA, protein, and activity in response to different levels of environmental lipids in both BF and PF cells. I also delineated the mechanisms by which TbACC expression and activity is regulated by phosphorylation in response to altered lipid environments. In the third …

Stromal-Epithelial Interactions Modulate Cross Talk Between Prolactin Receptor And Her2/Neu In Breast Cancer, Cong Xu

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The tumor microenvironment is a crucial factor in breast tumorigenesis. Tumor epithelial cells maintain 3D structure in tumor stroma and they interact with soluble factors secreted by stromal cells such as cancer associated fibroblasts (CAFs) or directly with the extracellular matrix (ECM). Recent studies have shown that the hormone prolactin (PRL) promotes the proliferation and survival of breast cancer cells in part via the transactivation of human epidermal growth factor receptor 2 (HER2), also known as Neu in rodents. A PRL receptor (PRLR) antagonist, G129R, has been demonstrated not only to be able to directly inhibit PRLR activation but also …

Spidroin N-Terminal Domain: A Ph Sensor In The Spider Silk Assembly Process, William Gaines

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Spider silks are protein-based fibers with remarkable mechanical qualities. Perhaps even more impressive is the spinning process in which the spider silk proteins (spidroins) are assembled from a highly soluble storage state into a well-ordered and insoluble fiber. Indeed, the ordered arrangement of spidroins, which is endowed by the spinning process, is the basis of fiber strength. However, the forces driving fiber assembly and the mechanisms by which spidroins respond those forces are only poorly understood. Spidroins have a tripartite domain architecture consisting of a large and repetitive central domain flanked by small, non-repetitive N- and C-terminal domains. Both terminal …

The Role Of Car And Pxr In Toxicant Sensitivity, Linda Mota

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The Constitutive Androstane Receptor (CAR) and the Pregnane X Receptor (PXR) are nuclear receptors of significant importance in the regulation of enzymes that metabolize, detoxify and eliminate compounds from the body. In this study we assessed the protective role of CAR and PXR in the basal and inducible regulation of Cytrochrome P450s (CYPs), and the potential of CAR and PXR to help protect individuals from the organophosphate, parathion and the plasticizer, nonylphenol, putatively due to improved metabolism and elimination. Knockout models of these receptors were used to model susceptible populations such as children that are known to have lower CAR …

Genomic, Proteomic And Metabolomic Approaches To Study Drought Responses In Aquilegia, David Henry

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Global population is expected to increase 30% by 2040, which will result in an increased need for crop production to feed the growing population. Combined with projected increased drought conditions worldwide, plant genetic research is necessary to gain a deeper knowledge of the molecular factors involved in plant drought response in order to engineer crop species with improved drought tolerance. Aquilegia has been recently developed as a model species for gene exploration based on its ability to thrive in a wide variety of environments including arid locations. An attractive asset of Aquilegia is its evolutionary position, equidistant between rice and …

Development Of Novel Prolactin And Growth Hormone Receptor Agonists And Antagonists, John Langenheim

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Potential indications for human prolactin (hPRL) and human growth hormone (hGH) are the support and sustainment of lactation and the enhancement or reconstitution of the immune system when under dysregulation. A prolactin receptor (PRLR) antagonist, hPRL-G129R (G129R), and a PRLR and growth hormone receptor (GHR) antagonist, hGH-G120R (G120R), have been developed which may be useful for the treatment of breast cancer since PRLR is elevated in a majority of human breast tumors and makes cancer cells highly sensitive to the mitogenic and anti-apoptotic activity of hPRL and hGH.

As a single agent, G129R is more cytostatic than cytotoxic to human …

The Role Of Prolactin And Its Antagonist In Her2/Neu Tumorigenesis, Michele Scotti

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Purpose: To study the role of prolactin (PRL) and its antagonist, G129R, in HER2/Neu tumorigenesis. Specifically, to investigate the interaction between the oncogene HER2 and the PRL receptor (PRLR) signaling pathways for designing effective combinational therapeutics for breast cancer.
Experimental Design: The combination effects of G129R and an anti-HER2 antibody, Herceptin, were tested against HER2-overexpressing human breast cancer cell lines, T-47D and BT-474, using cell based assays and xenografts established in athymic mice. Furthermore, four different bitransgenic mouse lines co-expressing the murine version of HER2 and PRL or G129R were generated. The mammary tumor incidence, characterization of mammary gland development, …