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The Impact Of Nitric Oxide On Dendritic Cell Metabolism, Julia Priscilla Snyder

Graduate College Dissertations and Theses

Dendritic cells (DCs) are sentinel immune cells capable of directly sensing and responding to pathogens. Upon pathogen recognition, DCs undergo a process of activation that allows them to participate in the proinflammatory response at the site of infection and to initiate the adaptive immune response through antigen presentation to T cells. Because activated DCs serve as the critical link between innate and adaptive immunity, modulating DC activation could be a powerful tool in various clinical contexts such as vaccine design. DC activation is accompanied by widespread changes in metabolism including the rapid upregulation of glycolysis, which is sustained in DCs …

Mitochondrial Dynamics Regulation Of The Lung Epithelial Response To Complex Allergen, Sierra White

Graduate College Dissertations and Theses

Asthma is a chronic inflammatory disease of the lungs that affects roughly 25 million Americans, costing the United States upwards of $80 billion annually in management and economic loss. The airway epithelium, which serves as the first line of defense against insults in the lung, are now appreciated as key contributors to initiation of this disease. A key regulator of the epithelial response to allergens and other inhaled irritants that can induce an allergic asthmatic response is the mitochondria. During an allergic response, the airway epithelial energy requirement changes, and mitochondrial function is altered, enhancing production of reactive oxygen species, …

Thyroid Hormone Receptor Beta Inhibits Pi3k Signaling And Glycogen Metabolism In Anaplastic Thyroid Cancer, Cole Davidson

Graduate College Dissertations and Theses

Thyroid cancer is the most common endocrine malignancy, and the global incidence has increased rapidly over the past few decades. While differentiated thyroid cancers often respond to standard therapies, there are no durable long-term treatment options for anaplastic thyroid cancer (ATC). The limited treatment options highlight a need for a deeper understanding of the molecular signaling in these aggressive tumors for development of more effective therapies.Non-steroidal nuclear receptors, such as thyroid hormone receptors (TRs), are an emerging class of therapeutic targets and tumor suppressors in thyroid and other cancers.Loss of expression of the tumor suppressor thyroid hormone receptor beta (TRβ) …

Spatial And Temporal Control Of The Kinesin Motors Kif11 And Kif22 In Mitosis, Alex Frances Thompson

Graduate College Dissertations and Theses

Mitosis requires the control of mechanical forces generated by kinesin motors to ensure equal segregation of chromosomes into two daughter cells. Two kinesins contributing to these forces are KIF11 (or Eg5), which crosslinks and slides anti-parallel microtubules, and KIF22 (or Kid), which binds to microtubules and chromosome arms. This work addresses how post-translational modifications and pathogenic mutations alter the structure and function of KIF11 and KIF22.

The homotetrameric kinesin KIF11 is subject to acetylation at lysine 146, a residue in the a2 helix of the motor domain. The effect of this acetylation was assessed at the single molecule and cellular …

Defining Regional Lung Extracellular Matrix Composition: Implications In Disease And Repair Following Injury, Evan T. Hoffman

Graduate College Dissertations and Theses

Chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are chronic lung diseases with significant worldwide impact and poor end-stage prognoses. Despite both diseases differing greatly in pathology, both COPD and IPF are hallmarked by drastic alterations to the extracellular matrix (ECM) within distinct anatomical lung regions. These alterations negatively impact cellular regeneration, and subsequently, lung homeostasis, physiology, and repair following injury. Whole decellularized lungs, stripped of cellular material while retaining lung ECM structure and composition, have previously provided complex models for both high-throughput proteomic evaluation of lung ECM as well as ex vivo culture models to study the …

Visualizing The Forces Exerted During 3d Motility By Toxoplasma Gondii, Rachel Stadler

Graduate College Dissertations and Theses

Intracellular parasites of the phylum Apicomplexa cause pervasive human diseases and are responsible for millions of deaths annually. The apicomplexan, Toxoplasma gondii, causes the disease toxoplasmosis and can infect most warm-blooded vertebrates. These parasites can cause blindness in their hosts. In immunocompromised individuals, the infection can lead to brain lesions and death. T. gondii uses a unique form of cellular motility to invade cells of its host, traverse numerous biological barriers, and disseminate throughout the host. These parasites move with an attachment-dependent mechanism called gliding. In the “linear motor model” of parasite motility, the parasite’s myosin motor, TgMyoA, is thought …