Life Sciences Commons^™

Enhancing Therapeutic Approaches For Melanoma Patients Targeting Epigenetic Modifiers., Maria Gracia-Hernandez, Zuleima Munoz, Alejandro Villagra

Biochemistry and Molecular Medicine Faculty Publications

Melanoma is the least common but deadliest type of skin cancer. Melanomagenesis is driven by a series of mutations and epigenetic alterations in oncogenes and tumor suppressor genes that allow melanomas to grow, evolve, and metastasize. Epigenetic alterations can also lead to immune evasion and development of resistance to therapies. Although the standard of care for melanoma patients includes surgery, targeted therapies, and immune checkpoint blockade, other therapeutic approaches like radiation therapy, chemotherapy, and immune cell-based therapies are used for patients with advanced disease or unresponsive to the conventional first-line therapies. Targeted therapies such as the use of BRAF and …

Evaluating The Biological Activities Of Novel Histone Deacetylase Inhibitors (Hdaci) In Adherent And Nonadherent Tumor Cell Lines, Samer Alanani

Theses and Dissertations

Epigenetic dysregulations are linked to many human diseases including neurodegenerative disorders, immunodeficiencies, cardiac disease, and most notably cancer. Changes in the mechanisms of histone modifications have been recognized as hallmarks of carcinogenesis. One of these modifications is histone acetylation which is regulated by the activities of histone acetyltransferases (HATs) and histone deacetylases (HDACs). The reversible actions of these enzymes govern the acetylome and maintain its balance allowing for activation and repression of gene transcription. However, aberrant overexpression of HDACs in certain tumors is associated with decreased levels of transcription leading to tumor progression and survival. Hence, small-molecule histone deacetylase inhibitors …

Evolutionary Mechanisms For Host Resistance To Tumor Growth And Subsequent Cancer Cell Counter-Adaptations, Arig Ibrahim Hashim

USF Tampa Graduate Theses and Dissertations

Cancer is well-recognized as an evolutionary system, as first proposed by Cairns and Nowell more than 60 years ago. In an evolutionary context, cancers growing in vivo typically consist of heterogeneous subpopulations of cells that interact with each other and with host cells through selection forces operating at many temporal and spatial scales. Moreover, the tumor environment comprises more than just cancer cells; it includes a rich cancer stroma and cancer-driving molecules such as cytokines and metabolites. The tumor’s environment comprises intratumoral heterogeneity that often leads to therapy resistance attributed to the essential roles of many genetic and nongenetic mechanisms. …

Decoding The Equine Genome: Lessons From Encode, Sichong Peng, Jessica L. Petersen, Rebecca R. Bellone, Ted Kalbfleisch, N. B. Kingsley, Alexa Barber, Eleonora Cappelletti, Elena Giulotto, Carrie J. Finno

Department of Animal Science: Faculty Publications

The horse reference genome assemblies, EquCab2.0 and EquCab3.0, have enabled great advancements in the equine genomics field, from tools to novel discoveries. However, significant gaps of knowledge regarding genome function remain, hindering the study of complex traits in horses. In an effort to address these gaps and with inspiration from the Encyclopedia of DNA Elements (ENCODE) project, the equine Functional Annotation of Animal Genome (FAANG) initiative was proposed to bridge the gap between genome and gene expression, providing further insights into functional regulation within the horse genome. Three years after launching the initiative, the equine FAANG group has generated data …

Decoding The Equine Genome: Lessons From Encode, Sichong Peng, Jessica L. Petersen, Rebecca R. Bellone, Theodore S. Kalbfleisch, N. B. Kingsley, Alexa M. Barber, Eleonora Cappelletti, Elena Giulotto, Carrie J. Finno

Veterinary Science Faculty Publications

The horse reference genome assemblies, EquCab2.0 and EquCab3.0, have enabled great advancements in the equine genomics field, from tools to novel discoveries. However, significant gaps of knowledge regarding genome function remain, hindering the study of complex traits in horses. In an effort to address these gaps and with inspiration from the Encyclopedia of DNA Elements (ENCODE) project, the equine Functional Annotation of Animal Genome (FAANG) initiative was proposed to bridge the gap between genome and gene expression, providing further insights into functional regulation within the horse genome. Three years after launching the initiative, the equine FAANG group has generated data …

The Regulation Of Plant Vegetative Phase Transition And Rejuvenation: Mirnas, A Key Regulator, Tajbir Raihan, Robert L. Geneve, Sharyn E. Perry, Carlos M. Rodriguez Lopez

Horticulture Faculty Publications

In contrast to animals, adult organs in plants are not formed during embryogenesis but generated from meristematic cells as plants advance through development. Plant development involves a succession of different phenotypic stages and the transition between these stages is termed phase transition. Phase transitions need to be tightly regulated and coordinated to ensure they occur under optimal seasonal, environmental conditions. Polycarpic perennials transition through vegetative stages and the mature, reproductive stage many times during their lifecycles and, in both perennial and annual species, environmental factors and culturing methods can reverse the otherwise unidirectional vector of plant development. Epigenetic factors regulating …

Exploring Epigenetics As A Tool For Population Assessment And Conservation In Large Marine Predators, Andria Paige Beal

FIU Electronic Theses and Dissertations

Worldwide, many large marine predator populations are in decline. These populations can be difficult to study due to the extensive home ranges and migration patterns often exhibited by these species. Molecular tools are therefore necessary to measure specific parameters on these populations that would otherwise be nearly impossible to obtain. This dissertation pioneers the use of environmental epigenetic approaches for that purpose, and specifically the epigenetic modification known as DNA methylation, using sharks and small cetaceans as model organisms. This work is organized into five chapters. Chapter I is an introductory chapter that lays out the fundamentals of environmental epigenetics …

Effects Of A Novel, Non-Toxic Histone Deacetylase Inhibitor On Hippocampal Memory Formation, Histone Acetylation, And Bdnf Gene Expression In Male Mice, Sarah Brianna Beamish

Theses and Dissertations

Memory dysfunction is a common symptom of aging, neuropsychiatric disorders, and neurodegenerative disorders, yet truly effective treatments for memory loss do not exist. De novo gene transcription is a molecular requirement for long-term memory formation. The transcription of genes related to synaptic plasticity and learning are regulated in part by histone acetylation, an epigenetic mechanism that regulates chromatin accessibility. Pharmacological compounds that maintain histone acetylation, called histone deacetylase inhibitors (HDACi), enhance memory by preventing deacetylation of core histone proteins, which initiates binding of transcriptional machinery to open chromatin. Therefore, HDACi are potentially promising therapeutics that could be used to prevent …

Unveiling Global Roles Of G-Quadruplexes And G4-22 In Human Genetics, Ruth Barros De Paula

Dissertations & Theses (Open Access)

G-quadruplexes are non-B DNA structures formed by four or more runs of repeated guanines that confer unique features to living organism’s genomes. These sequences are enriched in regulatory regions, such as promoters and 5’ UTRs, and have distinct regulatory roles in both health and disease states. Even though previous studies showed the impact of G4 in gene expression, none of them summarized the location-specific effect of G4. Also, there is no broad understanding about the most common G4 repeat in the human genome, named here as G4-22, and how it links to the evolution of mammals and their biology. In …

Successful Atac-Seq From Snap-Frozen Equine Tissues, Sichong Peng, Rebecca Bellone, Jessica L. Petersen, Theodore S. Kalbfleisch, Carrie J. Finno

Veterinary Science Faculty Publications

An assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) has become an increasingly popular method to assess genome-wide chromatin accessibility in isolated nuclei from fresh tissues. However, many biobanks contain only snap-frozen tissue samples. While ATAC-seq has been applied to frozen brain tissues in human, its applicability in a wide variety of tissues in horse remains unclear. The Functional Annotation of Animal Genome (FAANG) project is an international collaboration aimed to provide high quality functional annotation of animal genomes. The equine FAANG initiative has generated a biobank of over 80 tissues from two reference female animals and experiments to begin …

Epigenetic Mechanisms As Drivers Of Environmental Responses In Stony Corals, Javier A. Rodriguez Casariego

FIU Electronic Theses and Dissertations

The current pace of anthropogenic global change is imposing unprecedented conditions to biological systems. Coral reef ecosystems are particularly sensitive to the rapid increase in thermal anomalies and the changes in water chemistry caused by global change. However, although their decline has been documented worldwide, there are signs suggesting that stony corals harbor greater phenotypic plasticity than previously expected, sparking the interest in the study acquired non-genetic modifications (e.g., epigenome, microbiome) potentially increasing their resilience to global change, and constituting one of the main targets for intervention.

Epigenetics constitutes an exciting frontier to understand how the environment influences the regulation …

Multimodal Neuroimaging Of Hiv And Aging, Brandon Lew

Theses & Dissertations

HIV infection remains a significant contributor to disease burden, and with the success of antiretroviral therapies, the population of people with HIV is aging. A growing literature suggests a relationship between HIV-infection and a profile of age advancement, most notably in molecular studies of epigenetics. However, despite the widely-known high prevalence of HIV-related brain atrophy, functional deficits, and HIV-associated neurocognitive disorder (HAND), epigenetic age advancement has not been linked to HIV-related changes in neuroimaging metrics.

We applied three neuroimaging methods, structural MRI, resting state functional MRI, and resting state MEG, to study the brain structure and function of 121 virally-suppressed …

Discovery Of Novel Ubiquitin- And Methylation-Dependent Interactions Using Protein Domain Microarrays, Jianji Chen

Dissertations & Theses (Open Access)

Post-translational modifications (PTMs) drive signal transduction by interacting with "reader" proteins. Protein domain microarray is a high throughput platform to identify novel readers for PTMs. In this dissertation, I applied two protein domain microarrays identifying novel readers for histone H2Aub1 and H2Bub1, and H3TM K4me3. Ubiquitinations of histone H2A at K119 (H2Aub1) and histone H2B at K120 (H2Bub1) function in distinct transcription regulation and DNA damage repair pathways, likely mediated by specific "reader" proteins. There are only two H2Aub1-specific readers identified and no known H2Bub1-specific readers. Using a ubiquitin-binding domain microarray, I discovered the phospholipase A2-activating protein (PLAA) PFU domain …

Intergenerational Embodiment Of Stress : How The Broader Sociocultural Environment Can Shape Child Growth And Development, Elizabeth A. Holdsworth

Legacy Theses & Dissertations (2009 - 2024)

Childhood growth has been a means of identifying systemic, material inequalities within populations. The plasticity of growth is responsive to multiple environmental factors, most notably adequate nutrition, but also psychosocial stress. Psychosocial stress can be a function of the social and political economic ecology, reinforcing power hierarchies within societies. This dissertation proposes that childhood growth can also reflect inequality in the distribution of psychosocial stress exposure through mothers’ feelings of a chronically stressful environment conveyed through maternal-infant interactions.

Interplay Between Mirnas And Lncrnas: Mode Of Action And Biological Roles In Plant Development And Stress Adaptation, Xianxiang Meng, Aixia Li, Bin Yu, Shengjun Li

School of Biological Sciences: Faculty Publications

Plants employ sophisticated mechanisms to control developmental processes and to cope with environmental changes at transcriptional and post-transcriptional levels. MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs), two classes of endogenous noncoding RNAs, are key regulators of gene expression in plants. Recent studies have identified the interplay between miRNAs and lncRNAs as a novel regulatory layer of gene expression in plants. On one hand, miRNAs target lncRNAs for the production of phased small interfering RNAs (phasiRNAs). On the other hand, lncRNAs serve as origin of miRNAs or regulate the accumulation or activity of miRNAs at transcription and post-transcriptional levels. Theses lncRNA …

Connecting Environment And Phenotype: Deciphering Mechanisms Of Diapause Entry And Exit In The Annual Killifish Austrofundulus Limnaeus, Erin Monica Davis

Dissertations and Theses

Embryonic development is complex, dynamic, and dependent on environmental factors. Mechanisms of sensing and integrating environmental stimuli are diverse, and understanding these mechanisms in extant species can elucidate how complex phenotypes emerge from genomic information expressed in an environmental context. In Austrofundulus limnaeus, an annual killifish with alternative developmental trajectories, light and temperature are vital factors that determine if an embryo will enter a state of diapause. We hypothesize that embryos of A. limnaeus use the vitamin D₃ signaling pathway as a vehicle to incorporate these ecological signals into their developmental programing. Here we provide evidence of …

“Adopt-A-Tissue” Initiative Advances Efforts To Identify Tissue-Specific Histone Marks In The Mare, N. B. Kingsley, Natasha A. Hamilton, Gabriella Lindgren, Ludovic Orlando, Ernest Bailey, Samantha Brooks, Molly Mccue, Theodore S. Kalbfleisch, James N. Macleod, Jessica L. Petersen, Carrie J. Finno, Rebecca R. Bellone

Maxwell H. Gluck Equine Research Center Faculty Publications

No abstract provided.

Epigenetics As Driver Of Adaptation And Diversification In Microbial Eukaryotes, Agnes K.M. Weiner, Laura A. Katz

Biological Sciences: Faculty Publications

No abstract provided.

Opinion: Genetic Conflict With Mobile Elements Drives Eukaryotic Genome Evolution, And Perhaps Also Eukaryogenesis, Adena B. Collens, Laura A. Katz

Biological Sciences: Faculty Publications

Through analyses of diverse microeukaryotes, we have previously argued that eukaryotic genomes are dynamic systems that rely on epigenetic mechanisms to distinguish germline (i.e., DNA to be inherited) from soma (i.e., DNA that undergoes polyploidization, genome rearrangement, etc.), even in the context of a single nucleus. Here, we extend these arguments by including two well-documented observations: (1) eukaryotic genomes interact frequently with mobile genetic elements (MGEs) like viruses and transposable elements (TEs), creating genetic conflict, and (2) epigenetic mechanisms regulate MGEs. Synthesis of these ideas leads to the hypothesis that genetic conflict with MGEs contributed to the evolution of a …

“Adopt-A-Tissue” Initiative Advances Efforts To Identify Tissue-Specific Histone Marks In The Mare, N B. Kingsley, Natasha A. Hamilton, Gabriella Lindgren, Ludovic Orlando, Ernie Bailey, Samantha Brooks, Molly Mccue, T S. Kalbfleisch, James N. Macleod, Jessica L. Petersen, Carrie J. Finno, Rebecca R. Bellone

Department of Animal Science: Faculty Publications

No abstract provided.

Computational Analysis Of Non-Cpg Dna Methylation In The Mammalian Nervous System, Dennis Yawen Wu

Arts & Sciences Electronic Theses and Dissertations

Noncanonical forms of DNA methylation, especially non-CpG DNA methylation, play essential roles in the neuronal epigenome, and have only recently begun to be characterized. While most DNA methylation within mammals is found in a CG context and maintained by DNMT1, neurons contain uniquely high levels of non-CpG methylation, such that the total amounts of methylation in non-CpG contexts equals or surpasses the total amounts of methylation in CG contexts. Non-CpG methylation, unlike CpG methylation, cannot be maintained by DNMT1, and must be established by the de novo methyltransferase DNMT3A.One unique characteristic of non-CpG methylation compared to canonical CpG methylation is …

Targeting Epigenetic Mechanisms In Endometriosis, Sarah Elizabeth Brunty

Theses, Dissertations and Capstones

Endometriosis is a complex and elusive gynecological disease in which the inner lining of the uterus grows in locations outside of the uterus and forms lesions. It is known to affect 1 in 9 women of reproductive age worldwide. Symptoms of endometriosis include severe pain, heavy periods, and infertility. While multiple theories of origin exist, none fully encompass all aspects of the disease, although all theories agree that this is an inflammation-driven disease. Due to this, many researchers are turning towards epigenetics to explain the initiation and progression of endometriosis. However, what is causing these epigenetic changes is still a …

Initial And Advanced Stages Of Microbiota Establishment Within The Tsetse Fly, Miguel Eduardo Medina Munoz

Graduate Theses, Dissertations, and Problem Reports

Symbiosis is a long-term physical association between two or more species, although little is known regarding its evolutionary origins, particularly at the genetic level. Tsetse flies are the vector of African trypanosomes, causative agents of Human and Animal African Trypanosomiases. Tsetse provide an ideal model for studying initial and advanced stages of symbiosis. Tsetse have a simple digestive tract microbiota primarily consisting of two bacteria; the ancient mutualist Wigglesworthia glossinidia and the recently acquired Sodalis glossinidius. This work presents a chronological study in evolutionary terms of the history of a microbial-insect association. First, I present concepts on symbiosis and …

Arid4b Physically Interacts With Tfap2c In Mouse Embryonic Stem Cells, Ezgi̇ Gül Keski̇n, Jialiang Huang, Ni̇hal Terzi̇ Çi̇zmeci̇oğlu

Turkish Journal of Biology

Precise regulation of gene expression is required for embryonic stem cell (ESC) differentiation. Transcription factor (TF) networks coordinate the balance of pluripotency and differentiation in response to extracellular and intracellular signals. Chromatin factors work alongside TFs to achieve timely regulation of gene expression for differentiation process. Our previous studies showed that a member of the Sin3a corepressor complex, Arid4b, is critical for proper mouse ESC differentiation into mesoderm and endoderm. We found elevated histone 3 lysine 27 acetylation (H3K27Ac) in a subset of genomic loci in meso/endoderm directed arid4b? cells, coincident with their derepression. We reasoned that Sin3a complex may …

Characterization Of Higher Order Chromatin Structures And Chromatin States In Cell Models Of Human Herpesvirus Infection, Michael Mariani

Graduate College Dissertations and Theses

Human herpesviruses are ubiquitous pathogens worldwide with 90% of the global population infected with one or more Human herpesviruses (HHV’s) by adulthood. All herpesviruses have three unique life cycle stages. Upon resolution of a primary acute stage infection, they can establish a latent stage infection within the host cell nucleus. This stage is characterized primarily by transcriptional quiescence of the viral genome. Specific physiological conditions (e.g., cell stress) can cause the latent virus to enter the reactivation stage, often many years after resolution of the acute infection, in which the virus becomes replicationally active again. HHV’s are known to cause …