Life Sciences Commons^™

Role Of Topoisomerase Ii Alpha In Dna Topology And T Cell Responses During Chronic Viral Infections, Stella Chinyere Ogbu

Electronic Theses and Dissertations

The clearance of viruses is largely dependent upon the activation of T cells to generate a robust immune response. However, host responses are suppressed during chronic viral infections. In this thesis, we explored the role of Top2α in DNA topology in individuals with chronic HBV, HCV, and HIV infections. We found that Top2α protein expression and activity were low in T cells derived from chronically virus-infected individuals compared to healthy subjects. Using CD4⁺ T cells treated with Top2α inhibitor or poisoner as a model, we demonstrated that Top2α inhibition disrupts the DNA topology, suppresses DNA repair kinase (ATM), and …

The Distinct Expressions Of Integrins Αdβ2 And Αmβ2 Differently Regulate Macrophage Migration In 3d Matrix In Vitro And In Tissue During Inflammation, Kui Cui

Electronic Theses and Dissertations

Chronic inflammation is an essential mechanism during the development of cardiovascular and metabolic diseases. The outcome of diseases depends on the balance between the migration and accumulation of macrophages in damaged tissues. Macrophage motility is highly regulated by adhesive receptors, integrins. Namely, intermediate expression of integrin supports macrophage migration, while a high integrin density inhibits it. Our studies are focused on evaluation of the contribution of related integrins α_Dβ₂ and α_Mβ₂ to macrophage migration and development of chronic inflammation.

We found that integrin α_Dβ₂ is upregulated on M1-macrophages in vitro and …

Telomeric Dna Damage And Repair Machineries In Hiv Infection, Lam Nguyen

Electronic Theses and Dissertations

In this thesis, we investigated T cell homeostasis and DNA damage repair machineries in HIV infection. We found that the frequencies of CD4T cells were low, which is associated with cell apoptosis in HIV patients compared to healthy subjects. Importantly, these events were closely correlated to the increase in T cell exhaustion, senescence, DNA damage, and telomere attrition. Mechanistically, while the DNA damage sensors Mer11, Rad50, and NBS1 (MRN) complexes remained intact, the ataxia-telangiectasia mutated (ATM) kinase and its downstream checkpoint kinase 2 (CHK2) were significantly inhibited during HIV infection. Additionally, telomeric repeat-binding factor 2 (TRF2) that functions to protect …