Cell and Developmental Biology Commons^™

Exploring Β-Cell Function And Heterogeneity In Obese Sm/J Mice, Mario Alejandro Miranda

Arts & Sciences Electronic Theses and Dissertations

Pancreatic β-cells perform glucose-stimulated insulin secretion, a process required to maintain systemic glucose homeostasis. Obesity promotes glycemic and inflammatory stress, causing β-cell death and dysfunction, resulting in diabetes. Efforts to improve β-cell function in obesity have been hampered by observations that β-cells are highly heterogeneous, varying in morphology, function, and gene expression. There is great need to understand the breadth of β-cell heterogeneity in health and obesity to improve diabetic therapies.High fat-fed SM/J mice spontaneously transition from hyperglycemic-obese to normoglycemic-obese with age, providing a unique opportunity to study β-cell adaptation. Here, we show that as they resolve hyperglycemia, obese SM/J …

Discovery Of Sex Differences In Response To P53 Loss And Gain-Of-Function In Glioblastoma, Nathan Cuyle Rockwell

Arts & Sciences Electronic Theses and Dissertations

The tumor suppressor TP53 (p53) is the most frequently mutated gene in cancer and among the most mutated genes in brain cancer. Functionally, p53 is a transcription factor that, when activated by an array of stress stimuli, regulates a complex transcriptional program that contributes to a variety of antiproliferative pathways. The loss of p53 function (LOF), either through mutation, deletion, or inhibition by alterations in the proteins that regulate p53, removes an essential barrier to the unfettered proliferation and genomic instability that drive transformation. Unlike most tumor suppressors, many p53 mutations are missense mutations that lead to stable expression of …

The Genetic Basis Of Adaptation To Environmental Stress In Two Grass Genomic Model Systems, David Mitchell Goad

Arts & Sciences Electronic Theses and Dissertations

Plants are exposed to a wide variety of environmental stress in the wild and have developed an equally diverse set of adaptations to tolerate them. The evolutionary processes that have led to this functional diversification, and the specific genes and physiological mechanisms involved, are of immense interest to both evolutionary biologists and crop breeders. In this dissertation I investigate adaptation to different types of environmental stress in two economically important grass species, seashore paspalum (Paspalum vaginatum Sw.) and rice (Oryza sativa L.).

Seashore paspalum is a halophytic turfgrass that occupies habitats which can dramatically differ in salt concentration. Populations may …

Single-Cell Resolution Mechanistic Analyses Of Direct Lineage Reprogramming, Chuner Guo

Arts & Sciences Electronic Theses and Dissertations

End-stage organ failures remain a clinical challenge with an unmet need for medical therapies, with transplantation often being the only curative option. Despite advances in transplantation outcomes, organ shortage continues to limit the availability of cures to patients in need. The direct lineage reprogramming of one cell type to another is a promising avenue for therapy with the following advantages: (1) patient-specific cell sources, (2) direct conversion without reverting to pluripotency and the associated risk of teratoma formation, and (3) utilization of the cell type responsible for fibrotic scar formation for the engineering towards the desired cell fate. Nonetheless, many …

The Phylogeography Of Rare Central Tennessee Glade Endemics Trifolium Calcaricum And Viola Egglestonii, Rachel Ann Lyman

Arts & Sciences Electronic Theses and Dissertations

Endemic species are range-restricted to a particular type of habitat and generally occur in a few small populations. Often endemic species are threatened or endangered due to their geographic isolation and limited habitat breadth. Despite the fact that understanding factors that may have shaped the evolutionary history of a species with a narrow distribution can provide important insights for their management and conservation, little is known about the historical forces that gave rise to many endemic species. Endemic species can arise because of factors such as variation in climate, geographic barriers, and habitat specificity, or the combination of several of …

Transcriptional Control Of Dendritic Cell Function And Development, David Alexander Anderson Iii

Arts & Sciences Electronic Theses and Dissertations

Dendritic cells (DCs) are innate immune cells of the myeloid lineage that are specialized at pathogen recognition, cytokine production, and antigen presentation. Their functions and developmental pathways are largely conserved between mice and humans and mice. The DC lineage is composed of two major subsets, known as plasmacytoid DCs (pDCs) and classical DCs (cDCs). Research conducted to date suggests that the function of pDCs, limited to viral antigen recognition and type I interferon production, can be compensated by other immune cell lineages. On the other hand, there is a consensus that diversified subsets cDCs in mice and humans are essential …

Regulation Of Genome Architecture By Chromatin Remodeling In The Brain, Jared Vega Goodman

Arts & Sciences Electronic Theses and Dissertations

Brain development requires exquisite control of gene expression to establish and refine the proper circuitry of the nervous system. Gene expression control is under the purview of several cellular processes, including chromatin regulation in the form of DNA modification, histone modification, and nucleosome remodeling. Chromatin remodeling enzymes are the major effectors of nucleosome remodeling. These enzymes are clearly involved in brain development – mutations in chromatin remodeling enzymes are likely causative for neurodevelopmental disorders of cognition. Chromatin remodeling enzymes have discrete molecular functions and binding profiles and similarly control distinct phases of nervous system maturation. Chd4 is a Chd family …

Comprehensive Characterization Of The Genetic And Neoantigen Landscapes Of Follicular Lymphoma Patients Supports The Feasibility Of Personalized Cancer Vaccine Treatments, Cody Alexander Ramirez

Arts & Sciences Electronic Theses and Dissertations

Follicular lymphoma (FL) is the most common indolent non-Hodgkin’s lymphoma; however, it remains incurable with conventional therapies and is poorly responsive to checkpoint blockade. FL arises from B-lymphocytes and develops slowly (and often asymptomatically). A major research focus has been on how to avoid chemotherapy treatments, to limit the potential development of treatment-related side effects, and the risk of therapy-related second cancers. FL also carries an approximately 30% lifetime risk of transforming from an iNHL to more destructive lymphomas, which are associated with poorer prognosis. The most common transformation results in diffuse large B-cell lymphoma (DLBCL). However, many patients may …