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Full-Text Articles in Cell and Developmental Biology

Glutathionylation/Glutaredoxin Axis And The Regulation Of Epithelial Cell Plasticity And Fibroblast Activation In Airway Fibrosis, Shi Biao Chia Jan 2020

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 …


Pathological Consequences Of Pdi Oxidoreductase Activity On Viral Protein Maturation, Nicolas Chamberlain Jan 2020

Pathological Consequences Of Pdi Oxidoreductase Activity On Viral Protein Maturation, Nicolas Chamberlain

Graduate College Dissertations and Theses

The influenza A virus (IAV) causes severe respiratory illness in humans. Current treatments are rapidly becoming ineffective due to the emergence of viral resistance to available therapies such as oseltamivir and zanamivir. Given the impact of this virus there is an urgent need to explore novel targets for new treatments less susceptible to viral mutation; targeting host proteins utilized by the virus may avoid these limitations. It has been shown in vitro that interactions with host ER based protein disulfide isomerases (PDIs) are required for specific IAV proteins to reach their functional conformations. The viral proteins hemagglutinin (HA) and neuraminidase …


Redox Regulation Of Src Kinase: Implications For Innate Il-33 Signaling In Allergen Responses, Christopher Michael Dustin Jan 2020

Redox Regulation Of Src Kinase: Implications For Innate Il-33 Signaling In Allergen Responses, Christopher Michael Dustin

Graduate College Dissertations and Theses

The proto-oncogene tyrosine kinase Src is a ubiquitously expressed non-receptor tyrosine kinase involved in critical cellular functions including wound healing, migration, survival, and proliferation. Accordingly, aberrant Src signaling is also significantly involved in many diseases. Src is most well known as an oncogenic protein, however, there are emerging roles for Src signaling in various tissues involved in inflammatory diseases. One such tissue is the respiratory epithelium, which comprises the first line of defense against inhaled microbial, particulate, and chemical insults and is a critical nexus of innate immune signaling. Recent work has detailed the involvement of Src in many innate …


Anti-Tumor Signaling Of Thyroid Hormone Receptor Beta In Breast And Thyroid Cancer Cells, Eric Bolf Jan 2020

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 …


A Chemical Genetics Approach To Understand The Regulation Of Cryptosporidium Sexual Differentiation, Md Mahmudul Hasan Jan 2020

A Chemical Genetics Approach To Understand The Regulation Of Cryptosporidium Sexual Differentiation, Md Mahmudul Hasan

Graduate College Dissertations and Theses

Cryptosporidium species are eukaryotic intracellular parasites belonging to the phylum Apicomplexa. C. hominis and C. parvum cause diarrhea in humans which is self-limiting in immunocompetent adults but can have severe consequences in immunocompromised individuals and malnourished children. In developing countries, Cryptosporidium is one of the leading causes of moderate to severe diarrhea in children under five years of age. There is an urgent need for novel therapeutics against this parasite as the current treatment option is inadequate to treat the most vulnerable population to Cryptosporidium infection. Better understandings of the biology of Cryptosporidium would greatly enhance our capability to design …


Regulation Of Neuroinflammation After Ischemic Stroke By Astroglial Endothelin Receptor Type-B Signaling, John Mcinnis Jan 2020

Regulation Of Neuroinflammation After Ischemic Stroke By Astroglial Endothelin Receptor Type-B Signaling, John Mcinnis

Graduate College Dissertations and Theses

A large body of neuroscientific research has focused on reactive gliosis and glial scar formation because these are among the most prominent features of the cellular response to central nervous system (CNS) injury. Despite much progress in our understanding, controversy remains regarding the relative balance between the protective nature of the astroglial scar and its anti-regenerative features. Recent work suggests that astrocytes are heterogeneous in their resting state and in their reactivity. In traumatic injuries such as stroke and spinal cord injury, proliferative reactive astrocytes protect CNS tissue. By contrast, under neuroinflammatory and/or neurodegenerative conditions, neurotoxic astrocyte phenotypes may contribute …