Cell Biology Commons^™

Neonatal Islet-1+ Cardiovascular Progenitor Cell-Derived Exosomes And Their Functional Ability To Regulate Proliferation, Lourdes Ceja

Electronic Theses, Projects, and Dissertations

Heart failure affects many people around the world and can lead to disease progression and death. Consequently, new stem and exosome-based therapies are needed to address this major health issue and to provide therapeutic options that will improve outcomes for the increasing number of patients with heart disease. Stem cell-derived exosomes have captivated researchers’ attention over the past couple of years based on their functional role in cellular signaling which highlights the vital component of the secretome of stem and progenitor cells. Since neonates have significantly enhanced regenerative ability, we hypothesized that exosomes isolated from Islet-1+ expressing neonatal human cardiovascular …

Regulation Of Systemic And Cellular Metabolism In Prostate Cancer By Camkk2 And Elucidation Of Atgl’S Role In Disease Progression, Dominik Awad

Dissertations and Theses (Open Access)

The androgen receptor (AR) is the major driver of prostate cancer; hence, men with progressing disease are treated with androgen deprivation therapy (ADT). However, the majority of patients will relapse within 2-3 years due to multiple AR reactivation mechanisms. Thus, AR and the processes downstream of the receptor remain central drivers of prostate cancer. A direct target of AR is CAMKK2, a gene coding for the serine/threonine kinase Ca^2+/calmodulin-dependent protein kinase kinase 2 (CAMKK2), a protein upregulated in advanced prostate cancer. CAMKK2 modulates many of its pathological effects through the phosphorylation and activation of the 5' AMP-activated …

Grk3 Connects Angiogenesis And Neuroendocrine Differentiation In Prostate Cancer By Activating Hdac2 That Epigenetically Represses Tsp1 And Rest, Samira Naderinezhad

Dissertations and Theses (Open Access)

Prostate cancer (PCa) is the second most frequent cancer and the second leading cause of mortality in men in the United States. Neuroendocrine prostate cancer (NEPC) is the aggressive subset of castration-resistant prostate cancer (CRPC), found in ~20% lethal CRPC. The mechanisms underlying the progression of PCa to NEPC are still largely unclear, and new drug targets are desperately needed. NEPC is highly vascularized (angiogenic) and characterized by high expression of neuroendocrine markers. However, direct molecular links connecting angiogenesis and neuroendocrine differentiation are elusive.

Since epigenetic regulation has been implicated in NEPC progression, we examined expression patterns of 147 epigenetic …

The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with dismal prognosis. The only curative option for patients is surgery, but over 80% of patients are not surgical candidates. Unfortunately, PDAC is resistant to the three remaining options. PDAC is characterized by a profoundly hypoxic and immunosuppressive stroma, which contributes to its therapeutic recalcitrance. Alpha-smooth muscle actin+ (αSMA+) cancer-associated fibroblasts (CAFs) are the most abundant stromal component, as well as mediators of stromal deposition. The hypoxia-inducible factors (HIF1 and HIF2) coordinate responses to hypoxia, yet, despite their known association to poor patient outcomes, their functions within the PDAC tumor microenvironment (TME) …

Roles Of Oxidative Stress And Dna Methylation In Cigarette Smoking-Induced Accelerated Acute Myeloid Leukemia Progression, Mary Figueroa

Dissertations and Theses (Open Access)

Acute myeloid leukemia (AML) is a commonly diagnosed cancer in smokers. When current or former smokers have AML, they have worse survival compared to never smoking patients. This has been observed clinically for decades, but then it is unknown how smoking leads to worsened AML survival. Smoking causes oxidative stress and altered DNA methylation that persists for decades in peripheral blood mononuclear cells, but these changes from smoking have not been evaluated in the context of AML. We hypothesize that smoking-induced molecular changes, including altered DNA methylation associated with poor AML prognosis, promote AML. We developed a novel model to …

The Novel Role Of Dnmbp In Kidney Development, Brandy Walker

Dissertations and Theses (Open Access)

Congenital anomalies of the kidney and urinary tract (CAKUT) accounts for nearly one-fourth of all birth defects and more than 40% of pediatric end-stage renal disease, yet only 10-20% of CAKUT cases have a known monogenetic cause. Human kidneys are composed of up to a million epithelial tubules called nephrons. Disruption of nephron development is one of the many congenital anomalies that cause CAKUT, often resulting in chronic or end-stage renal disease which requires transplant. During nephron epithelialization, the formation of stable cadherin-mediated adhesion junctions is essential for maintaining cell-cell contacts. To understand the cell behaviors underlying abnormalities in renal …

Heat Stress Response And Excystation In Entamoeba Histolytica, Irem Bastuzel

All Dissertations

Entamoeba histolytica is a water- and food-borne intestinal protozoan parasite that causes amoebiasis and liver abscess and is responsible for symptomatic disease in approximately 100 million people each year leading to ~ 100,000 deaths. The most common disease transmission follows the oral-fecal route, but it can also be transmitted by mechanical vectors such as animals carrying the amoeba from contaminated sources to water systems. In rare cases, disease transmission has been recorded in some patients in which men-to-men sexual practices were preferred.

The life cycle of E. histolytica starts through ingestion of infectious cysts, which are non-dividing, quadri-nucleated structures surrounded …

Determining The Full-Length Structure Of Collagenase H Using Small-Angle X-Ray Scattering, Josie Carson

Chemistry & Biochemistry Undergraduate Honors Theses

Known to cause gas gangrene, Hathewaya histolytica secretes two sister collagenases, collagenase G (Col G) and collagenase H (Col H), to degrade the triple helical structure of collagen to further infection in a host. Individual domains of Col H have been crystalized in previous studies, but methods in x-ray crystallization of full-length Col H have been unsuccessful. Using Small Angle X-Ray Scattering (SAXS) data, atomistic modeling was used to generate multiple conformations of Col H while accounting for flexibility between domains. Full-length Col H was found to adopt a two-state conformational model exhibiting a majority compact and a minority elongated …

Engineering Of Ideal Systems For The Study And Direction Of Stem Cell Asymmetrical Division And Fate Determination, Martina Zamponi

Biomedical Engineering Theses & Dissertations

The cellular microenvironment varies significantly across tissues, and it is constituted by both resident cells and the macromolecules they are exposed to. Cues that the cells receive from the microenvironment, as well as the signaling transmitted to it, affect their physiology and behavior. This notion is valid in the context of stem cells, which are susceptible to biochemical and biomechanical signaling exchanged with the microenvironment, and which plays a fundamental role in establishing fate determination and cell differentiation events. The definition of the molecular mechanisms that drive stem cell asymmetrical division, and how these are modulated by microenvironmental signaling, is …

Determination Of The Functional Role Of Rab-Ggt In Physcomitrium Patens., Hyun Jin Jung

Electronic Theses and Dissertations

Protein prenylation, a common lipid post-translational modification, is required for growth and development in eukaryotes. Rab geranylgeranylation involves the addition of one or two 20-carbon geranylgeranyl moieties to Rab-GTPase target proteins, which regulate intracellular vesicle trafficking. The reaction is carried out by heterodimeric Rab geranylgeranyltransferase (Rab-GGT), which is composed of two associated α- and β-subunits, with the assistance of an additional protein called Rab escort protein (REP). Loss of function of the Rab-GGT α subunit RGTA1 has not been reported in any plant. While knockout of either of the two β subunits RGTB1 or RGTB2 results in …

Novel Functions For Arp2/3 Complex-Mediated Actin Networks Discovered In Chlamydomonas Reinhardtii, Brae M. Bigge

Dartmouth College Ph.D Dissertations

Chlamydomonas reinhardtii, a unicellular member of the Chlorophyta or Green Algae phylum, has been used for decades as a model for ciliary studies. Using this tool, previous work from our lab found a role for actin in ciliary assembly and maintenance. However, while the microtubule-based, membrane-ensheathed cilia of Chlamydomonas are highly conserved in relation to mammalian cells, the actin cytoskeleton is not as simple. Chlamydomonas contains two actin genes: IDA5, a conventional actin, and NAP1, a divergent actin. Here, we find that despite the divergence of NAP1, it is still able to interact with the actin nucleator, the Arp2/3 complex. …

A Conserved Mechanism For Hormesis In Molecular Systems, Sharon N. Greenwood, Regina G. Belz, Brian P. Weiser

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Hormesis refers to dose-response phenomena where low dose treatments elicit a response that is opposite the response observed at higher doses. Hormetic dose-response relationships have been observed throughout all of biology, but the underlying determinants of many reported hormetic dose-responses have not been identified. In this report, we describe a conserved mechanism for hormesis on the molecular level where low dose treatments enhance a response that becomes reduced at higher doses. The hormetic mechanism relies on the ability of protein homo-multimers to simultaneously interact with a substrate and a competitor on different subunits at low doses of competitor. In this …

Renal Cell Carcinoma Of Pelvic Kidney With Atypical Nodal Metastasis: A Diagnostic Challenge, Roshan-E-Shahid Rana, Muhammad Hammad Ather

Section of Urology

Ectopic pelvic kidney is a known congenital anomaly; however, the presence of renal cell carcinoma (RCC) in an ectopic kidney is rare with the evidence available in the form of a few case reports only. In this case report, we present a case of metastatic RCC in the pelvic kidney which became a diagnostic challenge because of atypical contrast-enhanced computed tomographic (CT) characteristics and unusual pattern of lymph node involvement including cervical lymph node in the absence of visceral metastasis. Because of its unusual location and uncertain vascular anatomy, ectopic kidney poses a surgical challenge. Owing to the rarity of …

Regulation Of The Heat Shock Response Via Lysine Acetyltransferase Cbp-1 And In Neurodegenerative Disease In Caenorhabditis Elegans, Lindsey N. Barrett

USF Tampa Graduate Theses and Dissertations

The decline of proteostasis is a hallmark of aging that is, in part, affected by the dysregulation of the heat shock response (HSR), a highly conserved cellular response to proteotoxic stress in the cell. The heat shock transcription factor HSF-1 is well-studied as a key regulator of proteostasis, but mechanisms that could be used to modulate HSF-1 function to enhance proteostasis during aging are largely unknown. In this study, we examined lysine acetyltransferase regulation of the HSR and HSF-1 in C. elegans. We performed an RNA interference screen of lysine acetyltransferases and examined mRNA expression of the heat-shock inducible gene …

Characterization Of The Responses To Chronic Stress In Caenorhabditis Elegans, Amy Laura Knight

Theses and Dissertations

Exposure to chronic temperature stress influences organismal phenotypes that are important for human health, agriculture, and ecology. In this thesis, the model organism Caenorhabditis elegans was used to study the effects of temperature stress on reproduction and lifespan. It was found that worms demonstrated a rapid shut down in egg-laying between 18-24 hours of exposure to 28°C. Despite this reproductive defect, the overall lifespan of worms was unaffected. At the molecular level, heat shock factor 1 (HSF-1), a regulator of the protective molecular pathway known as the heat shock response (HSR), was identified as important for progeny production during heat …

Genome-Wide Characterization Of Salmonella Typhimurium Genes Required For The Fitness Under Iron Restriction, Sardar Karash, Tieshan Jiang, Young Min Kwon

Poultry Science Faculty Publications and Presentations

Background

Iron is a crucial element for bacterial survival and virulence. During Salmonella infection, the host utilizes a variety of mechanisms to starve the pathogen from iron. However, Salmonella activates distinctive defense mechanisms to acquire iron and survive in iron-restricted host environments. Yet, the comprehensive set of the conditionally essential genes that underpin Salmonella survival under iron-restricted niches has not been fully explored.

Results

Here, we employed transposon sequencing (Tn-seq) method for high-resolution elucidation of the genes in Salmonella Typhimurium (S. Typhimurium) 14028S strain required for the growth under the in vitro conditions with four different levels of iron …

Deciphering Phosphoprotein Phosphatase Signaling Networks Using Proteomics Approaches, Brooke Brauer

Dartmouth College Ph.D Dissertations

Protein phosphorylation is a highly regulated mechanism of cell signaling control and its deregulation is implicated in disease. The kinases that catalyze the addition of phosphate groups onto their substrate proteins have been well studied, their signaling pathways mapped, and their effects on cell and organismal health observed. Knowledge of the phosphatases that reverse the reaction only recently began to come into focus. Phosphoprotein phosphatases (PPPs), long thought to be housekeeping enzymes, are now known to be exquisitely specific towards their substrates, but the exact nature of phosphatase regulation—both upstream and downstream of the phosphatase—is unclear.

PPPs recognize substrates through …

The Molecular Mechanism Of Load Adaptation By Branched Actin Networks, Tai-De Li, Peter Bieling, Julian Weichsel, R Dyche Mullins, Daniel A. Fletcher

Advanced Science Research Center

Branched actin networks are self-assembling molecular motors that move biological membranes and drive many important cellular processes, including phagocytosis, endocytosis, and pseudopod protrusion. When confronted with opposing forces, the growth rate of these networks slows and their density increases, but the stoichiometry of key components does not change. The molecular mechanisms governing this force response are not well understood, so we used single-molecule imaging and AFM cantilever deflection to measure how applied forces affect each step in branched actin network assembly. Although load forces are observed to increase the density of growing filaments, we find that they actually decrease the …

Investigating Roles Of 2 Novel Eklf Targets Involved In Erythropoiesis, Rose M. Gott

ETD Archive

Erythrocytes are primarily comprised of the oxygen carrying protein hemoglobin. Genetic mutations causing defects in the proper synthesis of hemoglobin result in various anemias. It is during the last phases of terminal erythroid differentiation that hemoglobin levels rise, making it a focus for therapeutic research. Fetal hemoglobin is comprised of ⍺-globin and gamma globin, then after a change in gene expression called hemoglobin switching which takes place after birth, adult hemoglobin is comprised of ⍺-globin and beta globin. We investigated hemoglobin switching and erythroid terminal differentiation by focusing on the master erythroid transcription factor Erythroid Krüppel-like Factor (EKLF). Data led …

Bio-Vascular 3d, Wisdom Shadrach

ORBioM (Open Research BioSciences Meeting)

Cardiovascular disease is a leading cause of mortality and morbidity across the world and according to the world health organization account for 32% of mortality rate globally. There still remain a need to develop better in vitro vascular models that would aid further in-depth understanding of cardiovascular pathogenesis and proposed therapeutic intervention.

This study intends to characterize four novel medically relevant synthetic polymer scaffolds, and one hydrogel, for their biocompatibility and potential application in a tissue engineered blood vessel (TEBV). A primary human endothelial cell line derived from the vein of the umbilical cord (HUVEC), and a human primary smooth …