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Full-Text Articles in Medical Sciences
Understanding The Protumorigenic Functions Of St6gal1 In Glioblastoma Stemness And Metabolism, Sajina Gc
Understanding The Protumorigenic Functions Of St6gal1 In Glioblastoma Stemness And Metabolism, Sajina Gc
All ETDs from UAB
Glioblastoma (GBM) is a rare but deadly cancer with median survival of just 15 months despite of aggressive treatment. Advancement in novel treatment modalities is hindered by its heterogeneous nature, which includes subsets of neural stem cell-like brain tumor initiating cells (BTICs) that are highly tumorigenic and therapy-resistant. bgalactoside a-2,6-sialyltransferase 1 (ST6Gal1) is elevated in most tumors including in normal and neoplastic stem cells. ST6Gal1 imparts oncogenic phenotypes such as invasion, apoptosis evasion, therapy resistance, TIC maintenance among others via sialylation of critical receptors like, Fas, TNFR1, EGFR and more. Yet ST6Gal1 led regulation of BTIC specific cell surface proteins …
The Role Of Dock3 In Normal Skeletal Muscle Function And Metabolism, Adrienne Samani
The Role Of Dock3 In Normal Skeletal Muscle Function And Metabolism, Adrienne Samani
All ETDs from UAB
DOCK (dedicator of cytokinesis) are proteins of an 11-member family of typical guanine exchange factors (GEFs) expressed almost exclusively in the brain and spinal cord. Human pathogenic DOCK3 variants have been identified to cause debilitating neuromuscular phenotypes such as muscle hypotonia, ataxia, and intellectual disability. Our lab identified DOCK3 as being strongly upregulated in Duchene muscular dystrophy (DMD), specifically in the skeletal muscles of DMD patient and mouse skeletal muscles. Global Dock3 KO mice on the dystrophin-deficient background exacerbated skeletal muscle and cardiac phenotypes. Similarly, DOCK3 KO mice appeared to have poor muscle architecture, locomotive activity, reduced myogenic fusion, impaired …
Transcriptional Regulation And Islet Transplantation Advantages Of Brown Adipose Tissue, Jessica D. Kepple
Transcriptional Regulation And Islet Transplantation Advantages Of Brown Adipose Tissue, Jessica D. Kepple
All ETDs from UAB
Metabolic disease encompasses various disorders, including obesity and diabetes, that negatively impact glucose and lipid homeostasis and increase the risk of co-morbidities. Adipose tissue, which regulates whole-body energy balance and acts as a specialized endocrine tissue, is negatively affected by obesity and diabetes. Brown adipose tissue (BAT) functions to dissipate excess energy as heat and therefore is an attractive target against metabolic disease. To develop more effective therapeutic strategies, BAT physiology and genetic regulatory mechanisms need to be better understood. This dissertation highlights studies seeking to illuminate novel transcriptional regulation and islet transplantation applications of BAT. We investigated the requirement …
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 …
The Role Of The St6gal-I Sialyltrasferase In Protecting Tumor Cells From Hypoxic Stress, Robert Brent Jones
The Role Of The St6gal-I Sialyltrasferase In Protecting Tumor Cells From Hypoxic Stress, Robert Brent Jones
All ETDs from UAB
An emerging concept in cancer biology is that surface glycosylation can play important roles in the regulation of cancer development and progression. Our group and others have shown that ST6Gal-I, a sialyltransferase that adds α2-6-linked sialic acids to N-glycosylated proteins, is upregulated in many cancers. Furthermore, data has indicated that ST6Gal-I acts as a pro-survival factor in a variety of settings, including resistance to chemotherapeutic drugs, radiotherapy resistance, and serum deprivation. The work presented in this dissertation adds to this understanding of ST6Gal-I’s role as a potent pro-survival factor and explores ST6Gal-I’s function in aiding tumor cells to survive hypoxic …
Novel Insights Into Neurofibromin Function And Human Neurofibromatosis Type 1 Mutations Using Genetically Engineered Mouse Models, Ashley Nicole Turner
Novel Insights Into Neurofibromin Function And Human Neurofibromatosis Type 1 Mutations Using Genetically Engineered Mouse Models, Ashley Nicole Turner
All ETDs from UAB
Loss of NF1 in different developmental and cellular contexts leads to unique physiological outcomes due to loss of neurofibromin function, including embryonic lethality, sporadic cancers, and the genetic disorder NF1. Neurofibromin acts as a tumor suppressor by modulation of RAS signaling, with other functions of this multi-domain protein being less clear. Even within the monogenic disorder of NF1, the clinical heterogeneity and mutational spectrum are immense, revealing the complexity underlying this disorder. There is a huge urgency and need for NF1 therapeutic treatments, and the same urgency to develop in vivo models to better understand NF1 that can be utilized …
Mechanistic Connections Between Metabolic And Differentiation Programs In T Cells, Danielle Alexandria Chisolm
Mechanistic Connections Between Metabolic And Differentiation Programs In T Cells, Danielle Alexandria Chisolm
All ETDs from UAB
Cellular metabolism is closely coupled to differentiation gene programs in many developmental systems. In part, this is due to a similar complement of transcription factors playing dual roles in regulating both the gene expression programs associated with specific metabolic pathways and the differentiation gene program of the cell. In T cells, T cell receptor- (TCR) and IL-2-sensitive transcription factors coordinate the programming of metabolic states with the effector and memory gene programs. Currently, our understanding of the mechanisms by which metabolic states contribute to the regulation of T cell differentiation gene programs is unclear. Metabolites are directly involved in epigenetic …
Altering Metabolism In The Tumor Microenvironment To Enhance Anti-Tumor Immunity For Lung Cancer, Cara Schafer
Altering Metabolism In The Tumor Microenvironment To Enhance Anti-Tumor Immunity For Lung Cancer, Cara Schafer
All ETDs from UAB
Overcoming cancer cell immune escape represents a fundamental obstacle in the treatment of cancer. Indoleamine 2,3-dioxygenase (IDO)-expressing myeloid-derived suppressor cells (MDSCs) are known to induce oxidative stress and alter amino acid metabolism within the tumor microenvironment (TME). The tryptophan (Trp)-catabolizing action of IDO not only promotes T cell tolerance and evasion but is also associated with impaired quality of life in cancer patients. We have previously demonstrated that a novel combination therapy, consisting of MDSC-depleting gemcitabine and a superoxide dismutase mimetic, prolonged survival of tumor-bearing mice by enhancing CD8+ memory T cell metabolism. We identify that combination therapy inhibits IDO …
The Alpha-Glucosidase Inhibitor Acarbose As A Calorie Restriction Mimetic To Modify Metabolic Outcomes In Mice, Rachel Ann Brewer
The Alpha-Glucosidase Inhibitor Acarbose As A Calorie Restriction Mimetic To Modify Metabolic Outcomes In Mice, Rachel Ann Brewer
All ETDs from UAB
Age-related diseases continue to be a leading cause of death. One of the only replicable methods proven to decrease age-related morbidity and mortality in multiple species is calorie restriction (CR). CR is difficult for human populations to implement, and has a number of associated risks and side effects. A CR mimetic could provide the healthspan- and lifespan-extending benefits of CR without the limitations. Acarbose (ACA), an α-glucosidase and α-amylase inhibitor approved to treat type 2 diabetes in humans, was recently identified as able to extend lifespan in healthy mice. The purpose of this research was to determine the effects of …
Energy Metabolism Of Platelets During Activation, Oxidative Stress And Storage, Saranya Ravi
Energy Metabolism Of Platelets During Activation, Oxidative Stress And Storage, Saranya Ravi
All ETDs from UAB
The principal function of platelets is to regulate hemostasis, and dysfunction of platelet aggregation or activation can lead to either excessive thrombotic or hemorrhagic complications. It has been shown that the ability to generate ATP and exposure to oxidative stress can affect platelet thrombotic potential. While platelet metabolism has been extensively studied, the importance of substrate availability and metabolic plasticity in regulating aggregation under physiological or pathological conditions is not well understood. In this dissertation, we examined the reliance of platelets on different metabolic substrates, the importance of ATP production for aggregation in response to thrombin stimulation, metabolic stress following …
Metabolic And Oxidative Regulation Of Neuronal Autophagy And Survival, Matthew Dodson
Metabolic And Oxidative Regulation Of Neuronal Autophagy And Survival, Matthew Dodson
All ETDs from UAB
Neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease and Huntington's disease are all characterized by metabolic dysfunction, increased oxidative damage to proteins and organelles, formation of proteinaceous inclusions, decreased autophagic and proteasomal function, and eventual neuronal and glial cell death. While our understanding of the mechanisms that underlie many of these pathologies is constantly growing, their exact cause, onset, interplay and progression still remain unclear. The gap between the description of disease pathologies and understanding the fundamental mechanisms of disease pathogenesis, progression and potential therapeutics to mitigate disease progression is still large. Based on the observation that altered glucose utilization, …
Mitochondrial Genetics Modify Body Composition, Metabolic Efficiency And Myocardial Metabolism, Kimberly Joanne Dunham
Mitochondrial Genetics Modify Body Composition, Metabolic Efficiency And Myocardial Metabolism, Kimberly Joanne Dunham
All ETDs from UAB
Obesity and cardiometabolic pathologies have reached epidemic levels worldwide over the last 30 years. Currently, the majority of research investigating possible genetic causes of obesity is focused on nuclear DNA (nDNA). While this has lead to the development of numerous animal models, it is apparent the etiology of obesity is more complex than single gene mutations. Recently it has also been suggested that mitochondrial DNA (mtDNA) mutations sustained during evolution as a consequence of our prehistoric environment may influence individual propensity and risk of disease. Contemporary human populations are no longer faced with the challenges of our ancestors such as …
Actions Of Grape Seed Extract In Rodent Brain And Differences In Metabolism Of Its Polyphenols In A Rodent Model Of Menopause, John Kenneth Cutts
Actions Of Grape Seed Extract In Rodent Brain And Differences In Metabolism Of Its Polyphenols In A Rodent Model Of Menopause, John Kenneth Cutts
All ETDs from UAB
Grape seed extract (GSE), a dietary supplement, has potential in the treatment and prevention of human chronic age-related diseases including cancers, cardiovascular diseases, and neurodegenerative diseases. GSE and adult hippocampal neurogenesis, independently, have enhanced learning and memory in rodents. We hypothesized that GSE enhances learning and memory, at least partially, by enhancing hippocampal neurogenesis. However, adult mice given GSE did not exhibit increased number of progenitor cells or new neurons, established markers of neurogenesis, in the dentate gyrus (DG). Also, 26-day-old pups whose mother was given GSE only while nursing had fewer new neurons in the DG compared to control …
Mitochondrial Genetics And Function In Cardiovascular Disease Susceptibility, Jessica L. Brenneman
Mitochondrial Genetics And Function In Cardiovascular Disease Susceptibility, Jessica L. Brenneman
All ETDs from UAB
While progress has been made in understanding the development and progression of cardiovascular disease (CVD), the mechanisms of CVD risk and initiation are not completely understood. It is widely accepted that CVD is the result of a combination of genetic and environmental factors but it is not known why some populations with otherwise similar risk factors appear more susceptible to CVD than others. It is also known that different strains of laboratory mice have distinct susceptibilities to CVD development. For example, C3H mice are resistant to diet induced atherogenesis whereas C57 animals are susceptible. We have also found that the …