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You searched for +publisher:"University of Notre Dame" +contributor:("Dr. Jeffrey Schorey, Committee Member"). Showing records 1 – 3 of 3 total matches.

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University of Notre Dame

1. Michelle Abadilla Favila. Host and Pathogenic Features That Drive Cellular Immune Response to <i>Leishmania spp. </i> Infection.

Degree: PhD, Biological Sciences, 2013, University of Notre Dame

Leishmaniases is a group of vector borne parasitic diseases that affects approximately 12 million people worldwide and results in diverse clinical pathologies, the initiating species often dictates these disease outcomes. Visceral leishmaniasis, the fatal form of the disease, results from infection with Leishmania donovani parasites while cutaneous leishmaniasis generally develops following infection with Leishmania major parasites. In the majority of L. major cases, lesions heal within several months and provide life-long immunity pending re-introduction of the disease. The source of this protective immunity to leishmaniasis is largely influenced by host cellular events leading to a robust IL-12 driven T-helper 1 (Th1) mediated response that produces high levels of IFN-γ which ultimately promotes anti- microbicidal production of nitric oxide (NO) and reactive oxygen species (ROS) that destroy invading pathogens. Macrophages (MPs) and Dendritic Cells (DCs) are major producers of IL-12. In this work, the overall goal of my research dissertation was to investigate the role of both host cell and pathogenic features that contribute to the IL-12 response elicited during Leishmania infection. To this end in vitro MP and DC infection assays coupled with host cell microarray based technologies and molecular genetics approaches were employed to address the interplaying host and pathogen determinants influencing the IL-12 response. Interestingly, previous studies have demonstrated a general suppression of IL-12 production in Leishmania infected macrophages that is tightly controlled at the level of IL-12p40 transcription. In chapter 2, we demonstrated that L. major inhibited promoter activity in RAW264.7 MPs that stably express Ets binding sites in the presence of (IFN-γ) or lipopolysacchride (LPS) stimulation, suggesting L. major may be inhibiting macrophage production of IL-12 by specifically targeting the Ets promoter element. Remarkably, human DCs exhibit a dynamic range in IL-12 production in response to Leishmania infection. IL-12 is generally enhanced during L. major infections, in contrast to, L. donovani infections which do not induce IL-12. In chapter 3, our microarray analysis of L. major infected human DCs (2, 4, 8, and 24 hrs) revealed a distinct type I IFN associated transcriptomic signature including upregulation of IRF2, IRF7, IRF9, and STAT1/2. L. major infected human DCs pre-treated with a neutralizing type I IFN pathway inhibitor, B18R, induced fewer IL-12p40 mRNA levels. Furthermore, in the context of L. donovani infections type I IFN genes IRF2, IRF7, and IFIT5 were not induced, a trend analogous to the IL-12p40 gene expression elicited by this species. These data indicated that the L. major induced IL-12 response is dependent upon a type I IFN response. In chapter 4, we investigated the role of pathogenic surface molecules on the ‘high- IL-12 inducing’ L. major background strain FV1. Parasite lipophosphoglycan (LPG) was previously characterized as a virulence determinant associated with… Advisors/Committee Members: Dr. Suzanne Bohlson, Committee Member, Dr. Jeffrey Schorey, Committee Member, Dr. Giles Duffield, Committee Member, Mary Ann McDowell, Committee Chair.

Subjects/Keywords: host cell; interleukin-12; leishmania

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Favila, M. A. (2013). Host and Pathogenic Features That Drive Cellular Immune Response to <i>Leishmania spp. </i> Infection. (Doctoral Dissertation). University of Notre Dame. Retrieved from https://curate.nd.edu/show/ww72b853p7q

Chicago Manual of Style (16th Edition):

Favila, Michelle Abadilla. “Host and Pathogenic Features That Drive Cellular Immune Response to <i>Leishmania spp. </i> Infection.” 2013. Doctoral Dissertation, University of Notre Dame. Accessed October 19, 2018. https://curate.nd.edu/show/ww72b853p7q.

MLA Handbook (7th Edition):

Favila, Michelle Abadilla. “Host and Pathogenic Features That Drive Cellular Immune Response to <i>Leishmania spp. </i> Infection.” 2013. Web. 19 Oct 2018.

Vancouver:

Favila MA. Host and Pathogenic Features That Drive Cellular Immune Response to <i>Leishmania spp. </i> Infection. [Internet] [Doctoral dissertation]. University of Notre Dame; 2013. [cited 2018 Oct 19]. Available from: https://curate.nd.edu/show/ww72b853p7q.

Council of Science Editors:

Favila MA. Host and Pathogenic Features That Drive Cellular Immune Response to <i>Leishmania spp. </i> Infection. [Doctoral Dissertation]. University of Notre Dame; 2013. Available from: https://curate.nd.edu/show/ww72b853p7q


University of Notre Dame

2. Cristina Ricardo Carter. Host-Pathogen Interactions:.

Degree: MS, Biological Sciences, 2008, University of Notre Dame

Leishmania species infect approximately 2 million people each year and 350 million people live in areas where they are at risk for infection. This vector-transmitted disease causes significant morbidity and mortality in tropical and subtropical regions of the world and its impact on global health has increased substantially in light of the rise of HIV infection. More recently, military incursions into Leishmania-endemic regions have highlighted the importance of this parasitic infection. Leishmania parasites are transmitted by the bites of infected female sand flies of the genre Lutzomyia in the Western Hemisphere and Phlebotomus in Asia, Africa and southern Europe. Infections present as self-limiting cutaneous lesions, mucocutaneous infection, or disseminated visceral disease responsible for the vast majority of fatalities. While extensive work has been done to characterize these infections, an appropriate treatment or vaccine is still not available. In this light, there is a pressing need to continue immunological research on this important parasite. Leishmania is the prototypical model of the T helper 1/T helper 2 (Th1/Th2) dichotomy of the immune response. These two extremes in response to infection have been best characterized in mouse models and lead to the control and elimination of pathology in case of Th1 and in uncontrolled infection and tissue damage in the case of Th2. Because Leishmania has been shown to utilize complement receptor 3 (CR3) to enter host cells and CR3 has been reported to downregulate Th1 responses, the role of CR3 in in vivo infection was characterized in Chapter 2. Our studies reveal that CR3 deficiency leads to heightened, albeit not complete, resistance to Leishmania major on a susceptible Balb/c background. A growing body of evidence indicates that Leishmania and other intracellular pathogens do not passively infect their hosts. Rather, many pathogens manipulate their hosts in such a way as to make them more hospitable to infection. In Chapter 3, we examine how CR3 affects host cell responses to L. major and how infection may act to modulate macrophage cell signaling events that would lead to appropriate activation and parasite killing. This includes looking at the activation of mitogen activated protein kinases (MAPK), the translocation of transcription factors into cell nuclei, and the production of effector molecules like nitric oxide (NO). Chapter 4 presents our investigation of CR3 and Leishmania infection in resistant C57BL/6 mice. This chapter will outline our results examining parasite phagocytosis, production of Th1-driving interleukin-12 (IL-12), and mitogen-activated protein kinases (MAPK) and interferon-gamma (IFN-γ)-mediated cell signaling. Chapter 5 draws on our research and the extensive body of literature that dissects Leishmania-host immune interactions to attempt to build a framework wherein we can begin to unravel the often contradictory mechanisms involved in Leishmania infection. In addition, we will consider… Advisors/Committee Members: Dr. Crislyn DSouza-Schorey , Committee Member, Dr. Jeffrey Schorey, Committee Member, Dr. Mary Ann McDowell, Committee Chair.

Subjects/Keywords: macrophage; complement receptor 3; leishmaniasis

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Carter, C. R. (2008). Host-Pathogen Interactions:. (Masters Thesis). University of Notre Dame. Retrieved from https://curate.nd.edu/show/4b29b566244

Chicago Manual of Style (16th Edition):

Carter, Cristina Ricardo. “Host-Pathogen Interactions:.” 2008. Masters Thesis, University of Notre Dame. Accessed October 19, 2018. https://curate.nd.edu/show/4b29b566244.

MLA Handbook (7th Edition):

Carter, Cristina Ricardo. “Host-Pathogen Interactions:.” 2008. Web. 19 Oct 2018.

Vancouver:

Carter CR. Host-Pathogen Interactions:. [Internet] [Masters thesis]. University of Notre Dame; 2008. [cited 2018 Oct 19]. Available from: https://curate.nd.edu/show/4b29b566244.

Council of Science Editors:

Carter CR. Host-Pathogen Interactions:. [Masters Thesis]. University of Notre Dame; 2008. Available from: https://curate.nd.edu/show/4b29b566244


University of Notre Dame

3. Emma A Lynch. Role and Regulation of the Proteasome in Epithelial Cell Adhesion and Migration.

Degree: PhD, Biological Sciences, 2006, University of Notre Dame

Epithelial cells disassemble their adherens junctions and “scatter’ during processes such as tumor cell invasion, as well as some stages of embryonic development. As migrating epithelia do not always exhibit changes in the composition of cadherin-catenin complexes, it is likely that post-transcriptional regulation of cellular processes can impinge on the assembly/disassembly of adherens junctions and contribute to the loss of cell polarity and the acquisition of a migratory potential, a process known as epithelial to mesenchymal transition (EMT). Control of actin polymerization is a powerful mechanism for regulating the strength of cell-cell adhesion. In this regard, studies have shown that sustained activation of Rac1, a well known regulator of actin dynamics, results in the accumulation of polymerized actin at cell-cell contacts and an increase in E-cadherin-mediated adhesion in epithelia. This study describes a link between the activity of the proteasome, the actin cytoskeleton and growth factor stimulated adherens junction disassembly. The disassembly of the adherens junction complex has been documented to be accompanied by a transient decrease in the cellular levels of Rac1-GTP. In this study, we demonstrate that Rac1-GTP (but not Rac1-GDP) is ubiquitinated and subject to proteasome-mediated degradation during the early steps of epithelial cell scattering. These findings delineate a mechanism for the down-regulation of Rac1 in the disassembly of epithelial cell-cell contacts and support the emerging theme that ubiquitin proteasome system (UPS)-mediated degradation of the Rho family GTPases may serve as an efficient mechanism for GTPase deactivation in the sustained presence of Dbl-exchange factors. Furthermore, we provide insight into the control of proteasome activity during E-cadherin-mediated adhesion. We show that arfaptin 2, an ARF interacting protein, regulates the disassembly of cell contacts via its effect on proteasome activity. Using cell-based assays, we show that expression of wild type arfaptin 2 inhibits proteasome activity and hence, the disruption of cell-cell contacts in MDCK cells despite the presence of scatter factor. Depletion of arfaptin 2 using small interfering RNA, results in the disorganization of E-cadherin-based contacts and increased cell volume. We have also begun to elucidate a role for the GTPase, Rap1, in the regulation of E-cadherin membrane traffic during adherens junction turnover in epithelial cells. Thus, this dissertation delineates a novel mechanism involved in the disassembly of cell-cell contacts during epithelial cell scattering and documents some key regulators of this process. Advisors/Committee Members: Prof. Joseph OTousa, Committee Member, Dr. Holly Goodson, Committee Member, Dr. Jeffrey Schorey, Committee Member, Dr. Crislyn DSouza-Schorey, Committee Chair.

Subjects/Keywords: epithelial cell scattering; proteasome; adherens junction; E-cadherin

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Lynch, E. A. (2006). Role and Regulation of the Proteasome in Epithelial Cell Adhesion and Migration. (Doctoral Dissertation). University of Notre Dame. Retrieved from https://curate.nd.edu/show/n296ww74m9w

Chicago Manual of Style (16th Edition):

Lynch, Emma A. “Role and Regulation of the Proteasome in Epithelial Cell Adhesion and Migration.” 2006. Doctoral Dissertation, University of Notre Dame. Accessed October 19, 2018. https://curate.nd.edu/show/n296ww74m9w.

MLA Handbook (7th Edition):

Lynch, Emma A. “Role and Regulation of the Proteasome in Epithelial Cell Adhesion and Migration.” 2006. Web. 19 Oct 2018.

Vancouver:

Lynch EA. Role and Regulation of the Proteasome in Epithelial Cell Adhesion and Migration. [Internet] [Doctoral dissertation]. University of Notre Dame; 2006. [cited 2018 Oct 19]. Available from: https://curate.nd.edu/show/n296ww74m9w.

Council of Science Editors:

Lynch EA. Role and Regulation of the Proteasome in Epithelial Cell Adhesion and Migration. [Doctoral Dissertation]. University of Notre Dame; 2006. Available from: https://curate.nd.edu/show/n296ww74m9w

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