Life Sciences Commons^™

The Role Of The Circadian Clock In The Intestinal Epithelium During Health, Regeneration, And Tumourigenesis, Kyle Stokes

Electronic Theses and Dissertations

The Earth’s axial rotation subjects its surface to constant periods of light and dark, this is known as photoperiod. Many organisms have adapted their physiology in accordance with this environmental constant by generating 24h rhythms in their physiological functions; these are known as circadian rhythms. Circadian rhythms are controlled by an endogenous time-keeping mechanism known as the circadian clock. Over 40% of the genome in mice and over 80% of the genome in primates has been shown to have 24h rhythms in transcription. The disruption of circadian rhythms through shiftwork, jetlag, or exposure to light at night is associated with …

Identification Of Chromatin Regulators Perturbed In Hematopoietic Stem And Progenitor Cell Aging, Eraj S. Khokhar

Electronic Theses and Dissertations

As lifespan is increasing globally, there is a critical need to identify strategies to extend healthspan and prevent chronic diseases into older age. The long-term goal of my research is to identify novel strategies to ameliorate aging-induced decline in hematopoietic stem cell (HSC) function. HSCs give rise to all mature blood and immune cells. With age, HSCs undergo defects in their differentiation ability which correlates with a decline in immune function. Comprehensive knowledge of gene regulatory and epigenetic mechanisms underlying this defect is a barrier to developing therapies to ameliorate aging-associated decline in HSC function. Therefore, my project focuses on …

The Dlk1-Meg3 Locus In Malignant Cells Of Proposed Primordial Germ Cell Origins., Zachariah Payne Sellers

Electronic Theses and Dissertations

Primordial germ cells (PGCs) are hypothesized to deposit hematopoietic stem cells (HSCs) along their migration route through the embryo during the early stages of embryogenesis. PGCs also undergo global chromatin remodeling, including the erasure and reestablishment of genomic imprints, during this migration. While PGCs do not spontaneously form teratomas, their malignant development into germ cell tumors (GCTs) in vivo is often accompanied by the retention of hypomethylation at the IGF2-H19 imprinting control differentially methylated region (DMR). Previous studies in bimaternal embryos determined that proper genomic imprinting at two paternally imprinted loci was necessary for their growth and development: Igf2-H19 and …

Cardiovascular And Hematopoietic Responses To Volatile Benzene Exposure., Wesley Tyler Abplanalp

Electronic Theses and Dissertations

The rapid and recent increase in the global epidemic of diabetes and cardiovascular disease suggests a strong component of the environment is contributing. Benzene is a ubiquitous volatile pollutant generated by cigarette smoke, automobile exhaust, wildfires and industrial activities. Consequently, it is found in almost all urban and rural air samples. Benzene is known to cause hematotoxicity and its metabolism generates oxidative stress. Although, benzene has been studied for many years, few investigations have probed what influence benzene exposure may have on other physiological processes. Here we hypothesize that benzene metabolism by hepatic-CYP450 2E1 generates oxidative stress and inflammation, which …

Role Of C-Kit In The Growth, Migration And Differentiation Of Human Cardiac Progenitor Cells., Bathri Narayan Vajravelu

Electronic Theses and Dissertations

The belief that adult mammalian heart lacks regenerative potential was challenged by the identification of c-kit positive cardiac progenitor cells (CPCs) in the heart. A recent phase I clinical trial (SCIPIO), has shown that autologous c-kit positive CPCs improve cardiac function and quality of life when transplanted into ischemic heart disease patients. c-Kit is a type III receptor tyrosine kinase and a common stem cell antigen. Stem cell factor (SCF) is the only known ligand for c-kit. Although c-kit is extensively used as an invariable marker of resident CPCs and shown to be important in the context of different cell …

The Role Of Stem Cells In Adipose Tissue Remodeling., Candice Reshay Holden 1988-

Electronic Theses and Dissertations

The work presented in this dissertation outlines the role of stem cells in the remodeling of adipose tissue under conditions of nutrient excess. Obesity-induced variations in adipose tissue stem cell distribution were uncovered by analysis of the stromal vascular fraction isolated from mice fed a high fat diet for several weeks. Bone marrow cell transplantation was used to determine the derivation of progenitor cells found in adipose tissue; and supplementation of depleted progenitor cell populations achieved via direct cell transplantation, helped to determine the contribution of these progenitor cells to the remodeling process. The dissertation is presented in five chapters …

Establishment Of Methods For Isolation Of Pnmt+ Cardiac Progenitor Cells, Namita Varudkar

Electronic Theses and Dissertations

Cardiovascular disease is the leading cause of death in the United States. Millions of patients suffer each year from endothelial dysfunction and/or debilitating myocardial damage resulting in decreased quality of life and increased risk of death or disablement. Current pharmacological approaches are only partly effective at treating cardiovascular disease, and hence, better strategies are needed to provide significant improvements in treatment options. Cardiac stem/progenitor cells have the potential to regenerate myocardial tissue and repair damaged heart muscle. There are many different types of cardiac progenitor cells, and each may have certain unique properties and characteristics that would likely be useful …

Hepatitis C Virus-Induced Hepatocellular Carcinoma: Cancer Stem Cell And Gene Therapy, Heba Samir Esmaeil Allam

Electronic Theses and Dissertations

Hepatitis C virus (HCV) is an important human pathogen that causes chronic hepatitis cirrhosis, steatosis and hepatocellular carcinoma (HCC) worldwide. Although current FDA-approved drugs are partially effective in the treatment of HCV, methods for cure and vaccine against the virus are still awaited. My thesis work presented here is focused on finding mechanism (s) of HCV-induced hepatocarcinogenesis and devising novel means to combat the HCV infection.

Herein, we have shown that long-term HCV expression results in the acquisition of cancer stem-like cells (CSCs) traits in liver derived cell lines. These traits include enhanced expression of putative stem cell markers DCAMKL-1, …