Life Sciences Commons^™

Glutathionylation/Glutaredoxin Axis And The Regulation Of Epithelial Cell Plasticity And Fibroblast Activation In Airway Fibrosis, Shi Biao Chia

Graduate College Dissertations and Theses

Asthma is a complex lung disorder that affects more than 200 million people across the globe. About 10% of asthmatics have severe disease accompanied by structural airway remodeling, including subepithelial fibrosis, airway smooth muscle cell hyperplasia, goblet metaplasia, and increased vascularization. Oxidative stress has been well-linked to asthma pathogenesis; however, the precise redox mechanisms governing the pathological states are slowly being teased apart in the recent years. Protein S-glutathionylation (PSSG) is a posttranslational modification where a three amino acid-peptide, glutathione, forms a disulfide bond with reactive cysteines of a protein thereby potentially changing the protein’s biological functions. Glutaredoxins are members …

Anti-Tumor Signaling Of Thyroid Hormone Receptor Beta In Breast And Thyroid Cancer Cells, Eric Bolf

Graduate College Dissertations and Theses

Dysregulation of the tumor suppressor thyroid hormone receptor beta (TRβ) is a frequent event in a number of solid tumors. As a nuclear hormone receptor, the primary function of TRβ is to regulate transcriptional activity in a ligand-dependent manner. However, TRβ activity is not well-defined and the pathways it regulates are not yet fully delineated. The two cancer types where TRβ is best studied are thyroid cancer and breast cancer. Interestingly, thyroid cancer is a risk factor for breast cancer and breast cancer is a risk factor for thyroid cancer, suggestive of an etiological link. Determining the molecular mechanisms of …

Novel Pausing Behavior Of The Kinesin-3 Family Member Kif1a Is Regulated By Tau, Dominique V. Lessard

Graduate College Dissertations and Theses

The unique relationship between neuronal structure and function is paramount for the complexity of the human nervous system. This relationship allows neurons to receive, process, and transmit information through many inter- and intracellular mechanisms. Axonal transport is an essential intracellular mechanism for neuronal health and viability. This process involves the transport of cellular cargo in the anterograde and retrograde direction along the axon, relaying materials between the soma and axon terminals, respectively. The necessity of an expedited form of transport becomes clear when one considers the magnitude of distance cargo must travel; in some cases, the axon can be up …

Tsrna Involvement In Promoting Breast Cancer Phenotypes, Stephanie Scalia

Graduate College Dissertations and Theses

The overall 5-year survival rate for woman diagnosed with breast cancer has increased significantly over the last 20 years. However, prognosis for women with stage IV, metastatic disease remains very poor. Women diagnosed with stage 0-III breast cancer have above an 85% chance of survival over a 5-year period while women diagnosed with stage IV breast cancer have a 5-year survival of less than 30%. A better understanding of the molecular mechanisms driving aggressive breast cancer is essential for the potential discovery of more targeted therapies to increase the survival rates for women diagnosed with stage IV breast cancer.

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Investigating The Runx1-Cbfβ Transcription Factor Complex As A Mitotic Gene Bookmark To Maintain The Normal Mammary Epithelial Phenotype, Eliana Moskovitz

Graduate College Dissertations and Theses

Disruption of normal mammary epithelial cell homeostasis through acquisition of

deleterious somatic and/or germline mutations leads to breast cancer development. Breast

cancer is the most commonly diagnosed cancer among women worldwide, and is

associated with the second highest amount of cancer-related deaths. Breast cancer

mortality rates are decreasing, likely through increased methods of detection and

development of targeted therapies. However, due to the complexity and heterogeneity of

the disease, the incidence rate remains high and the molecular events that lead to breast

cancer initiation and progression are poorly understood.

The epithelial-to-mesenchymal transition (EMT) is an essential molecular process

involved in …

Implications Of The Calm-Af10 Oncogenic Fusion Protein On Wnt Signaling In Leukemia, Jamie Lucille Deutsch

Graduate College Dissertations and Theses

Hematopoiesis is the complex differentiation process involving the formation of all blood cells from a common progenitor; the hematopoietic stem cell. Errors in this process can lead to acute leukemia, or a rapid accumulation of immature blood cells which hinders proper immune function. While survival rates of this devastating disease have increased dramatically over the last several decades, certain cytogenetic abnormalities remain risk factors for treatment resistance and relapse. One of these abnormalities is a chromosomal translocation involving the transcription factor, AF10

Mix-Lineage Leukemia, Translocated to, 10 (MLLT 10, referred to as AF10) is involved in several oncogenic translocations involved …

The Utilization Of Host-Derived Compounds By Gram-Negative Bacteria, Lauren Alexandra Hinkel

Graduate College Dissertations and Theses

The increase in multidrug resistance (MDR) among bacterial pathogens is an ongoing threat to public health, with the CDC estimating more than 2.8 million MDR infections in the United States each year, and greater than 35,000 deaths annually. Gram-negative bacteria possess intrinsic mechanisms to resist available therapeutics and are frequently responsible for difficult-to-treat nosocomial, blood stream, and soft tissue infections. In addition to biophysical and genetic MDR mechanisms, Gram negatives are metabolically versatile, enabling them to utilize host-derived nutrients to promote proliferation and colonization within the host. The metabolic versatility of Gram-negative bacteria is due, in part, to the transcription …

Investigations Into Signaling Mechanisms Of The Dcbld Receptor Family, Anna Schmoker

Graduate College Dissertations and Theses

Cells communicate to drive all biological processes during organismal development, homeostasis, and disease. Communication, or signaling, is carried out through an orchestration of complex sequential molecular interactions. A signal is typically initiated by an extracellular cue binding to a receptor on the cell membrane, which induces an intracellular response, resulting ultimately in cellular phenotypes such as growth, proliferation, migration, apoptosis or survival. Adaptor proteins are critical to signal transduction, as they facilitate the formation of protein complexes that transduce signals. CT10 regulator of kinase (CRK) and CRK-like (CRKL) form a family of adaptors that facilitate complex formation during developmental signaling, …