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2024

Doctor of Philosophy (PhD) Heersink School of Medicine

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Full-Text Articles in Medicine and Health Sciences

Non-Catalytic Regulators Of The Secretory Pathway, Peyton Vanwinkle Jan 2024

Non-Catalytic Regulators Of The Secretory Pathway, Peyton Vanwinkle

All ETDs from UAB

This thesis focuses on two key questions: 1) how are bone development and regeneration regulated by the CREB3L1 transcription factor; and 2) what is the mechanism of action of the endoplasmic reticulum resident protein JAGN1, which when dysregulated, causes severe congenital neutropenia (SCN)? CREB3L1 regulates bone development and regeneration in mammalian models by facilitating the expression of COL1A1 and components of the secretory pathway required for collagen secretion. We generated two zebrafish models of Creb3l1 dysfunction (creb3l1ΔbZIP/ΔbZIP and creb3l1TA+/TA+). Both models showed that Creb3l1 functions in regulating col1a1a transcription and overall regenerate size are conserved in zebrafish. However, we also …


Phosphate Drives Pulmonary Inflammation Through Fgfr1, Erk, And Akt Signaling, Seth Bollenbecker Jan 2024

Phosphate Drives Pulmonary Inflammation Through Fgfr1, Erk, And Akt Signaling, Seth Bollenbecker

All ETDs from UAB

Chronic kidney disease (CKD) is characterized as irreversible progressive loss of renal function and affects over one tenth of the global population. Although CKD-associated comorbidities contribute significantly to its mortality, the lungs are often not considered. Lung diseases make up three of the top six leading causes of death worldwide and share many comorbidities with CKD. Clinical reports show that CKD patients are more likely to develop obstructive and restrictive lung diseases, but the mechanisms underlying this propensity for CKD-associated pulmonary complications are unknown. Hyperphosphatemia and associated elevations of fibroblast growth factor (FGF) 23, two of many consequences of reduced …


Novel Roles Of Rab35 In Development And Disease, Kelsey Ruth Clearman Jan 2024

Novel Roles Of Rab35 In Development And Disease, Kelsey Ruth Clearman

All ETDs from UAB

As the largest and most dynamic family of GTPases within the mammalian cell, Rabs play an essential role as molecular switches in regulating intracellular vesicular trafficking and serve as significant signaling transducers. Over the last few decades, Rabs have been identified to regulate endocytic, transcytosis, and exocytotic pathways, and mutations in Rabs, or alterations in downstream effectors lead to embryonic lethality and diseases such as cancer and ciliopathies. Ciliopathies are a class of pathologies that result from defects in structure or function of the primary cilia. Primary cilia, found on virtually all mammalian cells, is a microtubule-derived appendage that relies …


Catecholamines And Catecholamine Resistance In Animal Models Of Metabolic Syndrome, Robert Follett Rosencrans Jan 2024

Catecholamines And Catecholamine Resistance In Animal Models Of Metabolic Syndrome, Robert Follett Rosencrans

All ETDs from UAB

The sympathetic nervous system is a key regulator of energy homeostasis, in part, through the control of white adipose tissue lipolysis. Sympathetic nerves modulate adipose tissue physiology through the release of catecholamines, particularly norepinephrine, onto alpha- and beta-adrenergic receptors (a-AR; B-AR). Lipolysis refers to the breakdown of triglycerides into glycerol and free fatty acids, often in response to activation of B2/3-AR. Beta adrenergic activation of lipolysis is widely known to be impaired in patients with metabolic syndrome and animal models thereof (catecholamine resistance). Recent studies have demonstrated that catecholamine regulation of adipokine release is also disrupted, suggesting that catecholamine resistance …


Investigating The Electrostatics Of Mucins As Key Contributors To Mucus Stasis In Cystic Fibrosis, Elex Skylar Rose Jan 2024

Investigating The Electrostatics Of Mucins As Key Contributors To Mucus Stasis In Cystic Fibrosis, Elex Skylar Rose

All ETDs from UAB

Cystic fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes a channel responsible for the transport of chloride and bicarbonate ions across the apical cell surface. In the respiratory tract, defective CFTR results in viscous and adherent mucus that becomes static within the airway, which leads to chronic infections, progressive lung damage, and early mortality. Historically, CF mucus stasis has been attributed to significant airway dehydration; however, growing evidence has demonstrated that aberrant electrostatic properties of mucins also contribute to mucus stasis in CF. Mucins are large, polymeric glycoproteins …


The Role Of Fibroblast Growth Factor Receptors In Inflammatory Airway Diseases, Molly Easter Jan 2024

The Role Of Fibroblast Growth Factor Receptors In Inflammatory Airway Diseases, Molly Easter

All ETDs from UAB

Chronic inflammation plays a role in the development and progression of airway diseases such as chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF). COPD is caused primarily by chronic cigarette smoke exposure. Conversely, CF is a single gene disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR). Although the causes of COPD and CF are different, there are common pathological features. Studies show that chronic inflammation plays a significant role in the pathogenesis of both COPD and CF. Moreover, chronic inflammation induces ageing-associated pathomechanisms like cellular senescence, which exacerbates chronic inflammation. Previous work demonstrates that …


Investigating Hiv-1 Transmission To Human Cervix Using Reporter Virus Technologies, Dana Frances Indihar Jan 2024

Investigating Hiv-1 Transmission To Human Cervix Using Reporter Virus Technologies, Dana Frances Indihar

All ETDs from UAB

Around 39 million people globally are currently infected with Human immunodeficiency virus 1 (HIV-1), more than half of whom are women. HIV-1 is a retrovirus that infects and depletes an individual’s immune cells, culminating in the development of acquired immunodeficiency syndrome (AIDS) if not managed with anti-retroviral therapies (ART). Most women acquire HIV-1 through heterosexual intercourse. However, the early mechanisms and virologic determinants of HIV-1 transmission to women remain unclear. Herein, we demonstrate transmitted/founder (TF) HIV-1 representing two genetically and pathogenically distinct subtypes (A and D) in vivo have distinct replication phenotypes in an ex vivo cervical explant tissue (CET) …