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Articles 1 - 16 of 16
Full-Text Articles in Medicine and Health Sciences
Investigation Of Proliferation Suppressors In Genetic Fitness Screens, Walter Frank Lenoir Iv
Investigation Of Proliferation Suppressors In Genetic Fitness Screens, Walter Frank Lenoir Iv
Dissertations & Theses (Open Access)
Innovation of CRISPR gene-editing technology has provided scientists genome manipulation tools that allowed rapid advancement of scientific capabilities and thus improved our ability to systematically study mammalian genetic functional profiles. Genome-wide CRISPR knockout screens conducted in collections of human cell lines can knock out genes at multiple loci, and have provided new insights into functional roles for independent genes. This method has launched massive efforts in looking across genetic backgrounds for context specific genetic vulnerabilities within cancer. Much of the research effort thus far has been spent on optimizing phenotype distinctions between essential, genes required for cell fitness, and non-essential, …
Beyond The Brain: A Study Of Α-Synuclein's Role In Bone And Adipose Tissue, Carolina A. Figueroa
Beyond The Brain: A Study Of Α-Synuclein's Role In Bone And Adipose Tissue, Carolina A. Figueroa
Electronic Theses and Dissertations
α-Synuclein is a polypeptide encoded by the Snca gene, highly expressed in neurons, but it is also found in bones and adipose tissue. Co-expression analysis showed that Snca regulates skeletal homeostasis, and its deletion reduced estrogen deficiency-induced bone loss and weight gain. It is a major component of Lewy bodies (LB) in Parkinson’s disease (PD), leading to progressive immobilization and a range of nonmotor symptoms, including osteopenia, body composition alterations and insulin resistance. This thesis aimed to determine α-Synuclein’s intrinsic role in bone and adipose homeostasis. We discussed the PD pathophysiology emphasizing aspects of bone health and metabolism. By using …
Quantifying Mid-Pregnancy Placental Metabolism In Guinea Pigs Fed A Lifelong Western Diet, Mary-Ellen E.T Empey
Quantifying Mid-Pregnancy Placental Metabolism In Guinea Pigs Fed A Lifelong Western Diet, Mary-Ellen E.T Empey
Electronic Thesis and Dissertation Repository
Maternal consumption of a Western diet (WD) has been linked to alterations in fetoplacental metabolic programming and risk for the exposed fetus to develop obesity, cardiovascular disease, and type II diabetes mellitus. It may also cause oxidative damage to the placental mitochondria. This thesis investigated the metabolic effects of a WD on placentae using a guinea pig model of pregnancy and hyperpolarized 13C MRI for metabolic quantification. It was hypothesized that placental glycolytic metabolism would increase, and placental oxidative metabolism would decrease in WD-fed sows. Control diet- and WD-fed, pregnant sows underwent metabolic MRI at 33 days gestation and …
Therapeutic Potential Of A Ketogenic Diet In The Treatment Of Major Depressive Disorder, Jordan A. Murrin
Therapeutic Potential Of A Ketogenic Diet In The Treatment Of Major Depressive Disorder, Jordan A. Murrin
Masters Theses, 2020-current
Major depressive disorder (MDD) is the second most common mental health condition and a leading cause of disability in the world. It is theorized that MDD develops from a combination of biological, psychological, and social stressors. The condition is typically treated using pharmaceuticals and psychotherapy. However, not all individuals with MDD have access to or choose to use these treatments, or may prefer to incorporate therapeutic lifestyle changes such as exercise, sleep, and healthy eating. Even with treatment, MDD can alter brain structure and function, leading to the development of comorbid mental health and chronic metabolic conditions like obesity, cardiovascular …
Tumor-Derived Exosomes Drive Immunosuppressive Macrophages In A Pre-Metastatic Niche Through Nf-Kβ Dependent Glycolytic Metabolic Reprogramming., Samantha M. Morrissey
Tumor-Derived Exosomes Drive Immunosuppressive Macrophages In A Pre-Metastatic Niche Through Nf-Kβ Dependent Glycolytic Metabolic Reprogramming., Samantha M. Morrissey
Electronic Theses and Dissertations
The formation of a pre-metastatic niche is a fundamental requirement for primary tumor metastasis. One of the defining characteristics of a pre-metastatic niche is infiltration of immunosuppressive macrophages. However, how these macrophages acquire their immunosuppressive phenotype remains largely unexplored. Here, we demonstrate that tumor-derived exosomes (TDE) polarize macrophages towards an immunosuppressive phenotype characterized by increased PD-L1 expression through NF-kB-dependent metabolic reprogramming in mice and humans. While NF-κB has previously been shown to act as a direct transcription factor for PD-L1, we report a novel mechanism where TDE-induced NF-κB activation drives PD-L1 expression by augmenting the glycolytic capacity of macrophages through …
Targeting Unique Domains Of Lsd1 Regulates Pediatric Glioma Innate Immunity And Nk Cell Metabolism, Cavan Bailey
Targeting Unique Domains Of Lsd1 Regulates Pediatric Glioma Innate Immunity And Nk Cell Metabolism, Cavan Bailey
Dissertations & Theses (Open Access)
Regulation of chromatin accessibility is a key mechanism of cellular identity, allowing different tissues to develop using the same DNA template. Cancers will often hijack these epigenetic pathways, reactivating developmental genes to drive growth and deactivating tumor suppressor and immune recognition genes. Chromatin-modifying proteins deposit and remove chemical moieties from histone tails to aid in governing gene expression, and these proteins have become a new therapeutic target in cancer. Traditional chemotherapeutics aim to damage DNA, dysregulate cell division, or block hormonal growth signals, but epigenetic therapy can target vulnerabilities specific to cancer cells and broadly change gene expression patterns that …
Function Of Gpr68 In Normal Hematopoiesis And Malignant Hematopoietic Diseases, Xiaofei He
Function Of Gpr68 In Normal Hematopoiesis And Malignant Hematopoietic Diseases, Xiaofei He
Theses and Dissertations
G protein-coupled receptor 68 (GPR68), as a proton-sensing receptor, is involved in numerous physiological processes. However, its specific functions in normal hematopoiesis and malignant hematopoietic diseases were unknown. Using a genetic loss of function approach (i.e. whole-body Gpr68-/- mouse model), B lymphocytes were reduced under stressed conditions, such as aging and hematopoietic regeneration. However, hematopoietic stem cells (HSC) from Gpr68-/- mice exhibited comparable function as HSC from wild type mice either under steady-state or upon stress. To determine whether the unaltered HSC function of Gpr68-/- mice was due to compensatory effects of Gpr68 in nonhematopoietic cells, a …
Functional Heterogeneity And Metabolic Adaptation Of Fibroblasts In Cancer, Lisa Becker
Functional Heterogeneity And Metabolic Adaptation Of Fibroblasts In Cancer, Lisa Becker
Dissertations & Theses (Open Access)
The tumor microenvironment is comprised of a multitude of cell types producing a milieu of cytokines, growth factors an extracellular matrix. Together, this intricate network of cells plays highly critical roles in determining a tumor’s potential to progress and metastasize. As the predominant cell types in the tumor microenvironment, cancer-associated fibroblasts (CAFs) are a key component in the regulation of tumor development and progression, but their exact functions in tumorigenesis remain poorly understood. This is partly due to the considerable heterogeneity amongst these cells, which confounds the characterization of their roles within the tumor microenvironment. Nevertheless, recent studies have provided …
Elucidating The Effects Of Glucose Toxicity On Tauopathy And Aging, Lukas Fluitt
Elucidating The Effects Of Glucose Toxicity On Tauopathy And Aging, Lukas Fluitt
Natural Sciences and Mathematics | Biological Sciences Master's Theses
Diabetes patients are at higher risk of contracting an age-related neurodegenerative disease such as Alzheimer’s disease (AD). However, the mechanisms which link these diseases are poorly understood. We hypothesize that glucose and elevated levels of the glycolysis by product advanced glycation end-products (AGEs), may be involved. AGEs accumulate with age and are elevated in both diabetic and AD patients. Diabetes is a metabolic disorder for which consumption of sugar-rich diets is a major risk factor and is central to etiology in the vast majority of cases.
We show that transgenic C. elegans expressing wild type (WT) human tau fed a …
Determining The Link Between Advanced Glycation Endproducts (Ages), Feeding, And Metabolism, Lauren Wimer
Determining The Link Between Advanced Glycation Endproducts (Ages), Feeding, And Metabolism, Lauren Wimer
Natural Sciences and Mathematics | Biological Sciences Master's Theses
Reactive a-dicarbonyls (a-DC’s), such as methylglyoxal (MGO), are unavoidable metabolites generated during glycolysis that accumulate with age and have been linked with chronic age-related metabolic diseases such as Diabetes Mellitus. Diabetes Mellitus is generally characterized by peripheral neuropathy and sustained hyperglycemia. Chronic hyperglycemia leads to an increase in glycolysis and a downstream increase in reactive a-DC’s. The human body has a natural method of detoxifying these a-DC’s. Glycolytic cells have enzymes which can detoxify a-DC’s, but if overwhelmed, a-DC’s can accumulate and react non-enzymatically with proteins, lipids and DNA to yield a group of molecules called advanced glycation end-products (AGEs). …
Metabolic Requirements Of Nk Cell Responses To Viral Infection, Annelise Yoo Mah-Som
Metabolic Requirements Of Nk Cell Responses To Viral Infection, Annelise Yoo Mah-Som
Arts & Sciences Electronic Theses and Dissertations
In recent years, the field of immunometabolism – the study of how specific changes in cellular metabolism regulate the function of diverse immune cell types—has grown exponentially. Several in vitro studies have examined the metabolic regulation of natural killer (NK) cells, which are first responders for viral infection and malignant transformation; however, much less is known regarding the role of metabolism in directing NK cell responses in vivo, such as during viral infection. In order to examine how NK cell antiviral function is regulated in vivo, we used a wellcharacterized infection with murine cytomegalovirus (MCMV) to assess NK cell cytokine …
Cyp2d6 Enzyme Polymorphisms And Their Effect On Opiate Metabolism, Blair Camille Runde
Cyp2d6 Enzyme Polymorphisms And Their Effect On Opiate Metabolism, Blair Camille Runde
Physician Assistant Scholarly Project Papers
The purpose of this research and systematic literature review is to determine if pharmacogenetic testing for the CYP2D6 enzyme responsible for the metabolism of several opiates leads to differences in serum levels, side effects, and treatment outcomes for patients with acute or chronic pain. In this review, the Pubmed and Embase databases were searched from January 1, 2014, to November 1, 2019. Exclusion criteria included studies published before 2014 and those not peerreviewed. For this review, 11 studies were included with designs such as prospective and retrospective cohorts, randomized control trials, systematic reviews, and meta-analyses. Much of the presented research …
Elucidating The Complex Signaling Events Driving Intestinal Stem Cell Plasticity Following Injury, Evan Lynch
Elucidating The Complex Signaling Events Driving Intestinal Stem Cell Plasticity Following Injury, Evan Lynch
Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics
Signaling events governing intestinal stem cell (ISC) homeostasis maintain the delicate balance of active self-renewal and passive differentiation to replenish intestinal epithelial cells (IEC) every 3-5 days. However, under certain contexts, ISC function is irreversibly compromised—requiring committed IEC lineages to dedifferentiate and regain “stemness”. In the current studies, we examine the signaling events driving epithelial cell responses to injury to expose pathologic failures in the healing response. Our specific goal is to tease out the cellular contexts that promote dedifferentiation to design effective therapeutics for disease conditions compromising ISC function.
First, we generated a novel transgenic animal using the epithelial-specific …
Apoe As A Metabolic Regulator In Humans, Mice, And Astrocytes, Brandon C. Farmer
Apoe As A Metabolic Regulator In Humans, Mice, And Astrocytes, Brandon C. Farmer
Theses and Dissertations--Physiology
Altered metabolic pathways appear to play central roles in the pathophysiology of late-onset Alzheimer’s disease (AD). Carrier status of the E4 allele of the APOE gene is the strongest genetic risk factor for late-onset AD, and increasing evidence suggests that E4 carriers may be at an increased risk for neurodegeneration based on inherent metabolic impairments. A new appreciation is forming for the role of APOE in cerebral metabolism, and how nutritional factors may impact this role. In chapter 1, the literature on nutritional interventions in E4 carriers aimed at mitigating disease risk is reviewed. Studies investigating the mechanism by which …
Investigations Of A Low Carbohydrate Ketogenic Diet As A Possible Treatment For Malignant Brain Tumors, Elizabeth Anaya
Investigations Of A Low Carbohydrate Ketogenic Diet As A Possible Treatment For Malignant Brain Tumors, Elizabeth Anaya
Regis University Student Publications (comprehensive collection)
Cancer is now the leading cause of premature death in the U.S. and second worldwide. However, all cancers on average have seen a 20% increase in 5-year survival in the last 30 years. This is not true for brain cancers which have only seen a 1% increase. Brain cancer is extremely hard to treat, costing the most money out of any other cancer. Nevertheless, Otto Warburg’s investigation of cancer as a metabolic disease has led to a variety of new promising treatments. One of these treatments involves starving cancer cells by cutting off their access to glucose, a key component …
Understanding And Targeting Glucose Transporter 3 In Glioblastoma, Catherine Jeanne Libby
Understanding And Targeting Glucose Transporter 3 In Glioblastoma, Catherine Jeanne Libby
All ETDs from UAB
Glioblastoma (GBM) is the most common adult primary malignant brain tumor with a median survival of about 15 months, even after aggressive treatment. Treatment of GBM is difficult for multiple reasons including the location of the tumor, tumor invasiveness, and the high degree of both inter-and intra-tumoral heterogeneity. Contributing to intratumoral heterogeneity are highly tumorigenic, stem-like tumor cells, with the capacity to self-renew and propagate the tumor, termed brain tumor initiating cells (BTICs). BTICs are also commonly therapy resistant, highly invasive, and metabolically plastic with elevated expression of glucose transporter 3 (GLUT3) allowing them to preferentially survive in low nutrient …