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Roles Of Dietary Bioactive Compounds In Gut Microbiota Modulation And Epigenetic Regulation In The Prevention Of Breast Cancer, Huixin Wu
All ETDs from UAB
Breast cancer (BC) is the second most common cancer and the second leading cause of cancer death among women in the United States. The average risk of a woman developing BC is about 13% according to American Cancer Society. Various genetic-related risk factors including inherited mutations of genes, and lifestyle-related risk factors such as physical inactivity, obesity, aging, smoking, and air pollution have been studied for cancer prevention and treatment. The currently existing treatment methods such as chemotherapy and neoadjuvant systemic therapy can induce adverse effects on patients. Therefore, cancer prevention has been of great interest to the society. Numerous …
A Tale Of Two Waves: The Role Of Genomic Enhancers In Regulating Transcriptional And Epigenetic Responses To Neuronal Activitiy, Robert A. Phillips Iii
A Tale Of Two Waves: The Role Of Genomic Enhancers In Regulating Transcriptional And Epigenetic Responses To Neuronal Activitiy, Robert A. Phillips Iii
All ETDs from UAB
The mesolimbic dopamine (DA) pathway, which consists of dopaminergic neurons that project from the ventral tegmental area (VTA) to the nucleus accumbens (NAc), is heavily implicated in drug addiction. Exposure to drugs of abuse results in increases in extracellular concentrations of DA in the NAc, which in turn activates an immediate early gene (IEG) expression program that primarily consists of activity-dependent transcription factors, such as the AP1 subunits Fos and JunB. IEGs engage a set of temporally and functionally distinct genes, termed the late response gene (LRG) expression program. While gene expression changes are critical for drug-dependent adaptations, two major …
Epigenetic Aberrations In Systemic Sclerosis And Systemic Lupus Erythematosus, Peter C. Allen
Epigenetic Aberrations In Systemic Sclerosis And Systemic Lupus Erythematosus, Peter C. Allen
All ETDs from UAB
Autoimmune diseases are a classification of more than eighty diseases where the immune system recognizes a self-antigen and mistakenly attacks the body’s own tissue, inducing inflammation a nd p otentially l eading t o d amage. Autoimmune diseases disproportionately affect women and develop at any age depending on the disease. The prevalence of some autoimmune diseases is increased in minority populations. Despite this, research into higher-risk populations is lacking. This highlights the need to contribute research into understanding autoimmune disease pathogenesis in diverse studies to understand why disease is more severe in these populations. We analyzed transcriptomes and methylomes of …
The Roles Of Repressive And Activating Epigenetic Factors In Vertebrates Neural And Neural Crest Development, Saeid Mohammad Parast
The Roles Of Repressive And Activating Epigenetic Factors In Vertebrates Neural And Neural Crest Development, Saeid Mohammad Parast
All ETDs from UAB
The vertebrate nervous system comes from specific regions of the ectoderm that comprises of the neural plate and the neural crest. Although genetic mechanisms governing vertebrate neural development have been investigated in depth, there is a knowledge gap regarding the roles of epigenetic mechanisms in this process. As epigenetic modulators, the COMPASS (also known as SET1/MLL complex) and HP1 proteins are responsible for regulating chromatin accessibility to transcription factors. COMPASS is responsible for deposition of activating histone H3K4 methylation marks at promoters and enhancers and thus creates open chromatin domains. The critical structural and regulatory subunits of COMPASS, Dpy30 and …
Examining Sex And Race Difference In Obesity Risk Factors In Older Americans Using Genetic And Lifestyle Data In Regards, Hairui Yu
All ETDs from UAB
Obesity is a prevalent chronic condition determined by social, psychological, behavioral, and biological factors. The prevalence of obesity remains a major public health issue and has continued to rise in the United States and around the world. People who are obese face a higher risk of cardiovascular and metabolic diseases. The fat mass and obesityassociated gene (FTO) is one of the most commonly identified genes in obesity-related research. This three-paper dissertation is aimed at improving understanding of sex and race differences in obesity risk factors in older Americans from genetic (FTO SNPs) and lifestyle (diet and physical activity) perspectives, using …
Role Of Dietary Compounds On Modulation Of Epigenetic Mechanisms And Gut Microbiota In Prevention Of Breast Cancer, Manvi Sharma
Role Of Dietary Compounds On Modulation Of Epigenetic Mechanisms And Gut Microbiota In Prevention Of Breast Cancer, Manvi Sharma
All ETDs from UAB
Breast cancer is the second leading causes of mortality among women living in the United States, representing a major public health issue. The current chemoprevention therapies can result into various adverse effects. Therefore, the use of dietary bioactive compounds has been of great interest due to their safer, non-toxic and efficacious properties. Sulforaphane (SFN) is an isothiocyanate found in various cruciferous vegetables such as broccoli sprouts (BSp) and green-tea polyphenols (GTPs) contain a major polyphenol, (-)-epigallocatechin-3-gallate (EGCG). These compounds have been shown to exhibit several anticancer properties especially as an epigenetic modifier. We investigated the efficacy of BSp or GTPs …
The Potential Roles Of Broccoli Sprouts (Bsp) And Green Tea Polyphenols (Gtps) In Prevention Of Mammary Cancer, Itika Arora
The Potential Roles Of Broccoli Sprouts (Bsp) And Green Tea Polyphenols (Gtps) In Prevention Of Mammary Cancer, Itika Arora
All ETDs from UAB
Cancer is one of the leading causes of death in the United States. Based on the American Cancer Society statistics, in 2021 1,806,590 new cancer cases and 605,520 cancer deaths are projected to occur in the United States. Amongst all, breast cancer (BC) is one of the most prevalent cancers that occurs in women. Various lifestyle factors such as alcohol intake, smoking, an unhealthy diet and physical inactivity may result in increased rates of BC risks (cancer-transition) by inducing mutations in DNA. Numerous epidemiological studies indicate that a diet rich in green tea polyphenols (GTPs), and/or cruciferous vegetables such as …
Epigenetic Regulation Of Gene Expression In Temporal Lobe Epilepsy, Rebecca Mary Hauser
Epigenetic Regulation Of Gene Expression In Temporal Lobe Epilepsy, Rebecca Mary Hauser
All ETDs from UAB
Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy and is characterized by seizures originating from the temporal lobe of the brain. A frequent seizure focus in TLE is the hippocampus, a structure located within the temporal lobe crucial for its role in memory formation. Seizures are an excess of synchronous excitation in the brain caused by a surplus of excitatory neurotransmission and a lack of sufficient inhibitory transmission. Coordinating the process of neuronal transmission is differential expression of genes likely resulting in an increase or decrease in proteins responsible for neural signaling such as neurotransmitters, ion …
Epigenetic Regulation By O-Glcnac Alters Anti-Fibrotic Gene Expression In Ipf Fibroblasts, Qiuming Wu
Epigenetic Regulation By O-Glcnac Alters Anti-Fibrotic Gene Expression In Ipf Fibroblasts, Qiuming Wu
All ETDs from UAB
Idiopathic pulmonary fibrosis (IPF) is an age-related chronic disease with a me-dian survival period of 3-4 years [1]. Although FDA has approved two drugs that may slow the disease process, there is no effective treatment [2]. IPF is characterized by the excessive deposition of collagen, which leads to deformation of alveolar structure, loss of lung function, and ultimately death [3]. Anti-fibrotic genes such as cyclooxygenase-2 (COX-2) and Heme Oxygenase 1 (HMOX-1) are usually suppressed in the pathogenesis of IPF [4-6], while the mechanisms responsible for the repression of anti-fibrotic genes in IPF are incompletely understood. More evidence has shown that …
Beyond Apoptosis: Insight Into The Complex Intracellular Networks That Govern Cell Fate, Hayley Neal Widden
Beyond Apoptosis: Insight Into The Complex Intracellular Networks That Govern Cell Fate, Hayley Neal Widden
All ETDs from UAB
The determination of cell fate is a dynamic process regulated by hundreds of proteins that converge into complex cell signaling pathways. Upon irreparable intracellular stress, a cell undergoes programmed cell death, a process known as intrinsic apoptosis. Apoptosis is regulated by the Bcl-2 family, a class of proteins that act either as pro-survival or pro-death signaling molecules. Due to the oncogenic upregulation of pro- survival Bcl-2 family proteins across human cancer cell types, a novel class of small molecule inhibitors called ‘BH3-mimetics’ have emerged as promising anti-cancer therapeutics currently under clinical investigation. Here, we highlight the crosstalk between anti-apoptotic Bcl-2 …
Genome-Wide Mirna Regulation Of Stress Susceptibility Across The Brain In A Rodent Model Of Early Life Stress, Lauren Alexis Allen Mckibben
Genome-Wide Mirna Regulation Of Stress Susceptibility Across The Brain In A Rodent Model Of Early Life Stress, Lauren Alexis Allen Mckibben
All ETDs from UAB
Early life stress (ELS) affects a significant portion of the US population in the form of various types of abuse and neglect, as well as household dysfunction and loss of a loved one, among others. Although these experiences happen early in life, they increase risk for mental health disorders, especially major depression (MDD), across the lifespan. MDD is a debilitating psychiatric disorder marked by periods of depressed mood and loss of pleasure in once enjoyable activities. Patients with MDD also report trouble sleeping, unintentional weight loss or gain, feelings of worthlessness, and suicidal ideation. MDD is associated with annual $100 …
Context Fear Memory Formation Is Regulated By Hippocampal Lncrna-Mediated Histone Methylation Changes, Anderson Alan Butler
Context Fear Memory Formation Is Regulated By Hippocampal Lncrna-Mediated Histone Methylation Changes, Anderson Alan Butler
All ETDs from UAB
The post-translational modification of histones regulates gene expression and is critical for the formation and maintenance of hippocampus-dependent long-term memories. Changes in gene-specific expression of various epigenetic marks during the aging pro-cess are sufficiently consistent as to be used as an aging landmark or epigenetic clock in both humans and other species; however, the molecular mechanisms which govern the application of these marks aging are poorly explored. Recently, long noncoding RNAs (lncRNAs) have been implicated as regulators of histone methyltransferases and other chromatin-modifying enzymes (CMEs). Despite the relevance of such mechanisms to both aging and memory formation, the behavioral relevance …
The Effects Of Saha And Egcg On Metastatic Potential In Triple-Negative Breast Cancer Cells, Kayla Lewis Steed
The Effects Of Saha And Egcg On Metastatic Potential In Triple-Negative Breast Cancer Cells, Kayla Lewis Steed
All ETDs from UAB
About 1 in 8 women will be diagnosed with breast cancer at some time in their lives, and more than 40,000 women will die due to breast cancer this year. Women do not die from localized breast cancer cases but from metastatic, or Stage IV, breast cancer (MBC). Over 150,000 women are currently living with MBC, and treatments focus on length and quality of life considering there is no cure. Triple-negative breast cancers (TNBC) do not respond to targeted therapies as they are lacking estrogen receptor alpha (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). They …
Genetic And Epigenetic Underpinnings Of End-Stage Human Heart Failure, Mark Emile Pepin
Genetic And Epigenetic Underpinnings Of End-Stage Human Heart Failure, Mark Emile Pepin
All ETDs from UAB
Heart failure (HF) is the clinical endpoint of numerous diseases that negatively impact the heart’s capacity to pump and/or fill with blood. A variety of genetic and environmental factors have been identified as critical determinants of HF susceptibility; however, these factors cannot independently explain the phenotypic diversity of human HF. Instead, a complex interplay has been theorized to exist between genetics and the environment, although the molecular underpinnings of this synergy remain poorly understood. Of the possible mechanisms, epigenetic influences are uniquely capable of explaining how acute stressors of the cardiac microenvironment trigger the stable – yet reversible – reprogramming …
Baf Chromatin Landscaping During Bone Formation And Maintenance, Tanner Cole Godfrey
Baf Chromatin Landscaping During Bone Formation And Maintenance, Tanner Cole Godfrey
All ETDs from UAB
Bone loss is a worldwide problem resulting in increased risk of fracture. Osteoblasts are responsible for bone synthesis; therefore, treatments promoting osteoblast differentiation and/or activity would result in increased bone formation. The regulation of DNA accessibility is a key mechanism controlling gene expression and cellular differentiation. BAF (BRG1 Associated Factor) mediated chromatin remodeling increases DNA accessibility by sliding or ejecting nucleosomes. This process can occur in a cell type specific manner based on the composition of BAF. In many tissue types, a unique combination of BAF subunits has been identified to be responsible for the maintenance or differentiation of that …
Effect Of Dietary Compounds In Epigenetic Modulation And Microbial Alteration And Their Roles In Breast Tumor Inhibition, Bidisha Paul
Effect Of Dietary Compounds In Epigenetic Modulation And Microbial Alteration And Their Roles In Breast Tumor Inhibition, Bidisha Paul
All ETDs from UAB
Breast cancer is a major cause of cancer death among women in the United States. Current methods of chemoprevention and therapy have cytotoxic effects and have several short-term and long-term side effects. Therefore, the use of natural dietary bioactive compounds has gained prominence as safe and effective agents of chemoprevention and therapy. Genistein (GE), an isoflavone found in soy products, has been shown to exhibit several anticancer properties, particularly as an epigenetic modifier. We have observed that GE has the ability to alter the gut microbiome of germ-free mice humanized with fecal transplants from breast cancer patients undergoing chemotherapy. We …
Combinatorial Withaferin A And Sulforaphane And Their Potential Roles In Breast Cancer Prevention And Therapy, Kendra Jeanine Royston
Combinatorial Withaferin A And Sulforaphane And Their Potential Roles In Breast Cancer Prevention And Therapy, Kendra Jeanine Royston
All ETDs from UAB
Cancer is a leading cause of death worldwide and is a devastating disease. Breast cancer is of particular interest because it is a major cause of cancer-related fatality in women in the United States. To date, more than 40,000 women are expected to die due to breast cancer and more than 200,000 will be diagnosed every year. Despite numerous advancements in the field, breast cancer remedies can be harsh and while life may be prolonged, the quality of life may decrease. This being said, preventive measures and less harsh treatment options are needed to help eliminate breast cancer as a …
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 …
Nf-Κb And Methyl-Lysine Signaling In The Epigenetic Regulation Of Memory, William Mitchell Webb
Nf-Κb And Methyl-Lysine Signaling In The Epigenetic Regulation Of Memory, William Mitchell Webb
All ETDs from UAB
Epigenetic mechanisms such as DNA methylation and histone methylation are critical regulators of gene transcription during memory consolidation and retrieval. However, the means by which these mechanisms are themselves initiated and directed to specific gene regions, and the extent to which these marks coordinate control of gene expression, remain poorly understood. In this dissertation, we explore the role of methyl-lysine signaling in the epigenetic regulation of gene expression in two contexts. First, we investigated the role of histone H3 lysine 4 tri-methylation (H3K4me3) and DNA 5-hydroxymethylation (5hmC) during memory retrieval, finding that these marks increased globally and at CpG-enriched coding …
Effects Of Proanthocyanidins In Combination With Resveratrol And Sulforaphane Respectively On Human Breast Cancer Cells, Yifeng Gao
All ETDs from UAB
Breast cancer is the second most common cancer and the second leading cause of death from cancer among women in the United States. Cancer prevention and therapy through use of phytochemicals that have epigenetic properties has gained considerable popularity during the past few decades. Such dietary components include but are not limited to grape seed proanthocyanidins (GSPs), resveratrol (Res) and sulforaphane (SFN). Here we report for the first time that GSPs and Res in combination dose- and time-dependently inhibited cell viability and posttreatment colony forming ability synergistically in MDA-MB-231 and MCF-7 human breast cancer cells, while GSPs and SFN in …
A Multi-Modal Approach To Sulforaphane-Mediated Chemoprevention Using The Epigenetic Network, Samantha Martin
A Multi-Modal Approach To Sulforaphane-Mediated Chemoprevention Using The Epigenetic Network, Samantha Martin
All ETDs from UAB
Colon cancer is the third most common diagnosed cancer in both women and men in the United States. It is reported that dietary factors are responsible for 70-90% of colon cancer cases. While some investigators have observed a direct correlation in high fat diets and cancer initiation, other studies have observed opposite effects mediated by fruit and vegetable consumption. Recently, studies have highlighted the importance of Epigenetics as it modifies gene expression without changing the DNA sequence. Notably, several nutritive compounds have been reported to alter epigenetic profiles in many cancer forms. SFN, an isothiocyanate found in cruciferous vegetables such …
Epigenetic Dysregulation In Levodopa-Induced Dyskinesia, David Anthony Figge
Epigenetic Dysregulation In Levodopa-Induced Dyskinesia, David Anthony Figge
All ETDs from UAB
Levodopa-induced dyskinesia (LID) is a persistent behavioral sensitization that develops after repeated levodopa (L-DOPA) exposure in Parkinson disease (PD) patients. LID is characterized by a “priming effect”, whereby initial administrations of L-DOPA trigger a sensitized biochemical and transcriptional response upon subsequent administrations of L-DOPA. In neurons, transcriptional regulation through dynamic changes to epigenetic modifications, including DNA methylation and histone acetylation, have been shown pivotal to many long-term behavioral modifications; however, their role in LID has been minimally explored. Using a rodent model, we show LID development leads to the aberrant expression of DNA demethylating enzymes and locus-specific changes to DNA …
Neurobiological Consequences Of Perinatal Ssri Exposure, Matthew Edward Glover
Neurobiological Consequences Of Perinatal Ssri Exposure, Matthew Edward Glover
All ETDs from UAB
Selective serotonin reuptake inhibitors (SSRIs) have been a mainstay pharmacological treatment for women experiencing depression during pregnancy and postpartum for nearly three decades. Recently, though, growing evidence indicates that early-life SSRI exposure triggers long-lasting behavioral abnormalities. Clinically, children exposed to SSRIs in early life exhibit increased internalizing behavior, reduced social behavior, and increased risk for depression in adolescence. Similarly, in rodents, perinatal SSRI exposure leads to increased traits of anxiety- and depression-like behavior. Interestingly, certain individuals are more susceptible to early-life SSRI exposure than others, suggesting that perinatal SSRI exposure poses greater risks for negative outcome within certain populations; however, …
Statistical Methodology To Improve The Understanding Of Dna Methylation Data, Lindsay Leigh Waite Jones
Statistical Methodology To Improve The Understanding Of Dna Methylation Data, Lindsay Leigh Waite Jones
All ETDs from UAB
The study of epigenetics involves the investigation of genomic elements that do not directly affect DNA sequence but are stable and preserved during cell division. One of the most commonly studied epigenetic elements is DNA methylation, which occurs when a methyl group is added to a cytosine residue in the DNA sequence. The advancement of technology to quantify DNA methylation, including bisulfite sequencing and bisulfite microarrays, has led to a large amount of available data. However, many questions still remain as to how to statistically analyze this data. This dissertation addresses some statistical concerns related to the analysis of DNA …
Altered Dna Methylation Contributes To Temporal Lobe Epilepsy And Associated Memory Deficits, Robert Ryley Parrish
Altered Dna Methylation Contributes To Temporal Lobe Epilepsy And Associated Memory Deficits, Robert Ryley Parrish
All ETDs from UAB
Status epilepticus (SE) triggers molecular mechanisms that underlie the cellular and network changes that occur during the development of temporal lobe epilepsy (TLE). Additionally, gene expression alterations occur during epileptogenesis and in the epileptic brain that contribute to the persistence of the phenotype. However, the underlying epigenetic mechanisms responsible for aberrant gene expression that occur with epilepsy require further investigation. This dissertation investigates how DNA methylation in the hippocampus affects epilepsy and contributes to the memory impairments associated with the disorder. We found that DNA methylation was altered in a hippocampal subregion specific manner in the epileptic brain, displaying altered …
Genetic And Epigenetic Changes Regulated By Bioactive Molecules In Cancer Therapeutics, Sabita Saldanha
Genetic And Epigenetic Changes Regulated By Bioactive Molecules In Cancer Therapeutics, Sabita Saldanha
All ETDs from UAB
Cancer biogenesis stems from genetic and epigenetic changes that regulate various signaling pathways responsible for growth, division, and proliferation. Genetic changes occur through mutations that contribute to loss of function, overexpression or repression of proteins involved in metabolic pathways. The changes place individuals at risk to diseases, including cancer. However, epigenetics is a mechanism of gene control that occurs through changes in chromatin structure without alterations to the DNA sequence and is mostly reversible. Epigenetic alterations have been implicated in colorectal cancers (CRCs), transforming normal colonic epithelial cells. Aberrant DNA methylation and chromatin modifications have been shown to contribute to …
The Role Of Histone Deacetylase Inhibitors In Ameliorating Memory Dysfunction Of An Alzheimer's Disease Mouse Model, Mark Kilgore
The Role Of Histone Deacetylase Inhibitors In Ameliorating Memory Dysfunction Of An Alzheimer's Disease Mouse Model, Mark Kilgore
All ETDs from UAB
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by amyloid beta plaques and neurofibrillary tangles, along with cognitive impairments that progress to dementia and eventually death. The development of drug treatments that rescue memory deficits could be a promising therapy given in the early stages of AD. In the following studies, we tested the potential for systemic treatment with histone deacetylase (HDAC) inhibitors to ameliorate cognitive deficits in a mouse model of AD. Using the APPSwe/PS1dE9 mouse model of AD, we showed that giving HDAC inhibitors systemically for 3 weeks reversed contextual memory deficits, stably maintained memories over a 2-week …
Epigenetic Regulation Of Hippocampus-Dependent Learning, Laura Qadri
Epigenetic Regulation Of Hippocampus-Dependent Learning, Laura Qadri
All ETDs from UAB
Knowledge of the molecular mechanisms that underlie learning and memory has advanced a great deal. Research into the role of epigenetics, or modifications above the genome, has the promise of providing an even greater understanding of the precise mechanisms involved in memory formation. Studies of epigenetic regulation of memory in the rodent hippocampus have primarily focused on associative learning using contextual fear conditioning. While these studies have provided valuable insight into the role that epigenetics plays in cognition, it remains to be seen whether the findings generalize to other forms of hippocampus-dependent learning. This work examines the role of epigenetic …
Epigenetic Markers In The Developing Postnatal Brain, Rebecca Kaye Simmons
Epigenetic Markers In The Developing Postnatal Brain, Rebecca Kaye Simmons
All ETDs from UAB
Epigenetic mechanisms provide a critical and plausible mechanism by which genes and the environment can interact and have been implicated in a number of diseases and disorders. In order to better understand how epigenetic mechanisms go awry in a diseased brain we must first understand how epigenetic mechanisms unfold during normal development. The present body of work begins to examine the role of DNA methylation in normal development and how it may contribute to a rodent model of emotion dysfunction. Using a variety of techniques, we evaluated the transcript, protein and functional output levels of DNA methyltransferase1, -3a, and -3b …
The Role Of Histone Methylation In The Medial Temporal Lobe During Long-Term Memory Formation, Swati Gupta
The Role Of Histone Methylation In The Medial Temporal Lobe During Long-Term Memory Formation, Swati Gupta
All ETDs from UAB
Several studies have established the importance of epigenetic regulation of gene transcription in the brain during memory consolidation. Epigenetic mechanisms involve modifying the DNA or the associated histone proteins to determine the transcriptional outcome of a gene. The work encompassed in this dissertation serves as an initial investigation for the role of histone lysine methylation mechanisms in regulating gene activation and suppression in the medial temporal lobe that includes entorhinal cortex (EC), hippocampus, and amygdala during memory consolidation. To this end, we found that di-methylation of histone H3 at lysine 9 (H3K9me2) which promotes gene suppression was specific to associative …