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Articles 1 - 15 of 15
Full-Text Articles in Medical Sciences
Irreversible Electroporation Potentiates Beta Glucan Induced Trained Innate Immunity: A Novel Combination Treatment For Pancreatic Adenocarcinoma., Matthew Woeste
Electronic Theses and Dissertations
Pancreatic cancer (PC) is a challenging diagnosis yet to benefit from advances in immune oncologic treatments. Irreversible electroporation, a non-thermal method of tumor ablation, is used in treatment of select patients with locally advanced unresectable PC and has potentiated the effect of certain immunotherapies. Yeast-derived particulate β-glucan induces trained innate immunity and successfully reduces murine PC tumor burden. This study tests the hypothesis that IRE may augment β-glucan-induced trained immunity in the treatment of PC. β-Glucan-trained pancreatic myeloid cells were evaluated ex vivo for trained responses and anti-tumor function after exposure to ablated and un-ablated tumor conditioned media. β-Glucan and …
Metabolic-Epigenetic Regulation Of Macrophage Polarization., Jordan T. Noe
Metabolic-Epigenetic Regulation Of Macrophage Polarization., Jordan T. Noe
Electronic Theses and Dissertations
Tumor-associated macrophages polarized to an M2 phenotype (M2-TAMs) promote neo-angiogenesis, tumor-stromal matrix remodeling, and immuno-evasion, which, collectively, contribute to immunotherapeutic resistance and reduced cancer patient survival. Highly glycolytic “Warburg” cancer cells produce lactate that independently drives naïve M0→immunosuppressive M2 (M0→M2) macrophage polarization, but the mechanisms have not been fully elucidated. The atypical cytokine macrophage migration inhibitory factor (MIF) is a fundamental underlying requirement for immunosuppressive M2 macrophage polarization. Still, it is unknown whether a molecular link exists between lactate-supported and MIF-dependent M2 macrophage polarization. Using a combination of gene expression assays, chromatin immunoprecipitation, and metabolomic analyses, we identified that M2 …
Sex-Based Differences In Microbiota Composition And Metabolomic Profiles Associated With Altered Macrophage Function And Protection From Lupus In Bwf1 Mice., James William Harder
Sex-Based Differences In Microbiota Composition And Metabolomic Profiles Associated With Altered Macrophage Function And Protection From Lupus In Bwf1 Mice., James William Harder
Electronic Theses and Dissertations
Systemic lupus erythematosus (SLE) is a complex and an insidious disease that is still not completely understood, and has very few treatment options. Those that are available are ineffective and/or have serious side effects. Both genetic and environmental factors contribute to the susceptibility and resistance to SLE, and understanding the environmental factors underlying this disease could lead to more effective prevention and/or treatment strategies. Like most autoimmune diseases, SLE is much more prevalent in females than males. While there are numerous factors that contribute to this lupus susceptibility, there is increasing evidence that the microbiota can strongly influence lupus progression, …
Harnessing The Power Of Trained Immunity In The Setting Of Pancreatic Cancer: A Novel Mechanism Of Immune Trafficking And Tumor Control., Anne Elena Geller
Harnessing The Power Of Trained Immunity In The Setting Of Pancreatic Cancer: A Novel Mechanism Of Immune Trafficking And Tumor Control., Anne Elena Geller
Electronic Theses and Dissertations
Despite the success of immunotherapy in many types of cancer, pancreatic adenocarcinoma (PDAC) has yet to benefit. Innate immune cells are critical to antitumor immunosurveillance and recent studies have revealed that these populations possess a form of memory, termed trained innate immunity, which occurs through transcriptomic, epigenetic, and metabolic reprograming. Though trained innate immunity has mostly been investigated in the context of infection, the induction of trained innate immunity could also protect against tumors, and specifically pancreatic tumors. Here, we demonstrate that yeast-derived particulate β-glucan, a known inducer of trained immunity, traffics to the pancreas following IP administration. This causes …
Development, Expansion And Role Of Myeloid-Derived Suppressor Cells In Post-Sepsis Immune Suppression, Tuqa Alkhateeb
Development, Expansion And Role Of Myeloid-Derived Suppressor Cells In Post-Sepsis Immune Suppression, Tuqa Alkhateeb
Electronic Theses and Dissertations
Myeloid-derived suppressor cells (MDSCs) numbers increase significantly in sepsis and are associated with high mortality rates. These myeloid cell precursors promote immunosuppression, especially in the late (post sepsis) stage. However, the mechanisms that underlie MDSC expansion and programming are not completely understood. To investigate these mechanisms, we used a cecal-ligation and puncture (CLP) mouse model of polymicrobial sepsis that progresses from an early/acute proinflammatory phase to a late/chronic immunosuppressive phase. Previous studies in our laboratory showed that microRNA (miR)-21 and miR-181b elevate levels of the transcription factor nuclear factor 1 (NFI-A) that promotes MDSC expansion. We report here that miR-21 …
Tissue-Resident Myeloid-Derived Suppressor Cells Modulate Immune Homeostasis In Healthy Adipose., Katlin Brooke Stivers
Tissue-Resident Myeloid-Derived Suppressor Cells Modulate Immune Homeostasis In Healthy Adipose., Katlin Brooke Stivers
Electronic Theses and Dissertations
Our goal with this study was to gain insight into the homeostatic immune cell network in healthy adipose tissue. Specifically, we sought to determine if the immature myeloid cells found in healthy and inflamed adipose were, in fact, tissue-resident myeloid-derived suppressor cells (MDSCs). Using various in vitro and in vivo methods, we have uncovered a population of CD11bHi Ly6CHi Ly6G- MDSCs resident in healthy adipose tissue. To the best of our knowledge this is the first time that these cells have been investigated and described in healthy adipose tissue. Systemic MDSC depletion lead to the accumulation of …
Plasmodium Impairs Antibacterial Innate Immunity To Systemic Infections In Part Through Hemozoin-Bound Bioactive Molecules., Christopher Lynn Harding
Plasmodium Impairs Antibacterial Innate Immunity To Systemic Infections In Part Through Hemozoin-Bound Bioactive Molecules., Christopher Lynn Harding
Electronic Theses and Dissertations
Despite efforts to decrease the global health burden of malaria, infections with Plasmodium species continue to cause over 200 million episodes of malaria each year which resulted in 405,000 deaths in 2018 [1]. One complication of malaria is increased susceptibility to invasive bacterial infections. Plasmodium infections impair host immunity to non-Typhoid Salmonella (NTS) through activities of heme oxygenase I (HO-I) )-induced release of immature granulocytes and myeloid cell-derived IL-10. Yet, it is not known if these mechanisms are specific to NTS. We show here, that Plasmodium yoelii 17XNL (Py) infected mice had impaired clearance of systemic Listeria monocytogenes (Lm) during …
Deciphering The Role Of Human Arylamine N-Acetyltransferase 1 (Nat1) In Breast Cancer Cell Metabolism Using A Systems Biology Approach., Samantha Marie Carlisle
Deciphering The Role Of Human Arylamine N-Acetyltransferase 1 (Nat1) In Breast Cancer Cell Metabolism Using A Systems Biology Approach., Samantha Marie Carlisle
Electronic Theses and Dissertations
Background: Human arylamine N-acetyltransferase 1 (NAT1) is a phase II xenobiotic metabolizing enzyme found in almost all tissues. NAT1 can additionally hydrolyze acetyl-coenzyme A (acetyl-CoA) in the absence of an arylamine substrate. NAT1 expression varies inter-individually and is elevated in several cancers including estrogen receptor positive (ER+) breast cancers. Additionally, multiple studies have shown the knockdown of NAT1, by both small molecule inhibition and siRNA methods, in breast cancer cells leads to decreased invasive ability and proliferation and decreased anchorage-independent colony formation. However, the exact mechanism by which NAT1 expression affects cancer risk and progression remains unclear. Additionally, consequences …
Ubqln1 : A Multi-Domain Protein With Multiple Functions., Zimple Kurlawala
Ubqln1 : A Multi-Domain Protein With Multiple Functions., Zimple Kurlawala
Electronic Theses and Dissertations
There are 5 Ubiquilin proteins (UBQLN1-4, UBQLN-L), which are evolutionarily conserved and structurally similar. UBQLN proteins have 3 functional domains: N-terminal ubiquitin-like domain (UBL), C-terminal ubiquitin-associated domain (UBA) and STI chaperone-like regions in the middle. Alterations in UBQLN1 gene have been detected in a variety of disorders including Alzheimer’s disease, Amyotropic Lateral Sclerosis and lung cancer. UBQLN1 has been largely studied in neurodegenerative disorders in the context of protein quality control. Several studies have hypothesized that the UBA domain of UBQLN1 binds to poly-ubiquitin chains of substrate and shuttles it to the proteasome via its UBL domain for degradation. UBQLN1 …
The Role Of Nicotine, A7 Nicotinic Acetylcholine Receptors And Extracellular Matrix Remodeling In Pulmonary Fibrosis., Glenn Ward Vicary
The Role Of Nicotine, A7 Nicotinic Acetylcholine Receptors And Extracellular Matrix Remodeling In Pulmonary Fibrosis., Glenn Ward Vicary
Electronic Theses and Dissertations
The median survival for idiopathic pulmonary fibrosis (IPF) patients from diagnosis is a dismal 3 years. This condition is characterized by pulmonary fibroproliferation and excess production and disordered deposition of extracellular matrix (ECM) proteins resulting in obliteration of the original tissue architecture, loss of lung function and eventual death due to respiratory failure. The main hindrance to the development of effective treatments against pulmonary fibrosis is the late detection of its progression and is often of unknown cause. Tobacco smoke represents the most important environmental factor linked to the development of pulmonary fibrosis, with over 60% of IPF patients current …
Immune Monitoring In Recipients Of Combined Living Donor Kidney And Hematopoietic Stem/Facilitating Cell Transplants., Mark Dewayne Badder
Immune Monitoring In Recipients Of Combined Living Donor Kidney And Hematopoietic Stem/Facilitating Cell Transplants., Mark Dewayne Badder
Electronic Theses and Dissertations
Solid organ transplantation coupled with a hematopoietic stem cell transplant from the organ donor allows for the recipient to cease immunosuppressive therapy after transplant via a chimeric immune system. This beneficial effect of stem cell transplants is negatively affected by graft versus host disease (GVHD). Better understanding of the donor and recipient’s immune system is vital to mitigating graft versus host disease and induction of donor chimerism without GVHD. In this study, flow cytometry was used to characterize immune cells of the recipients’ before and up to eighteen months post transplantation. The recipients were categorized into their respective chimeric groups. …
Porphyromonas Gingivalis Gingipains Induce A Pro-Inflammatory Extracellular Microenvironment : The Role Of Par-2 And Fibronectin., Jeffrey S. Marschall
Porphyromonas Gingivalis Gingipains Induce A Pro-Inflammatory Extracellular Microenvironment : The Role Of Par-2 And Fibronectin., Jeffrey S. Marschall
Electronic Theses and Dissertations
Periodontitis is a chronic inflammatory disease that is characterized by severe tissue destruction of the gingiva and other tooth supporting structures; if left untreated, tooth loss and disintegration of the alveolar bone occurs. This chronic inflammatory state has been linked to other systemic diseases such as cardiovascular disease, diabetes, rheumatoid arthritis, and Alzheimer’s disease. Porphyromonas gingivalis is the major pathogenic microbe in periodontitis. The main virulence factors of P. gingivalis are the Arg-aa and Lys-aa gingipains, which are proteolytic enzymes implicated in a plethora of activities that allow P. gingivalis to subvert the human immune system in the oral cavity …
Abin1 In The Pathogenesis Of Glomerulonephritis And The Novel Polocyte-Neutrophil Proinflammatory Axis., Erik Anderson Korte
Abin1 In The Pathogenesis Of Glomerulonephritis And The Novel Polocyte-Neutrophil Proinflammatory Axis., Erik Anderson Korte
Electronic Theses and Dissertations
Glomerulonephritis (GN) is the most common cause of end-stage renal disease worldwide and is characterized by deposition of immune complex, inflammation, proteinuria and podocyte damage. Immunosuppressive therapy is effective in less than 50% of patients, indicating that immunological activity is not the only relevant cause of kidney injury. While methods have been described for neutrophil-mediated immune activation, specific glomerular mechanisms for recruitment of neutrophils and development of GN have not been determined. Here I present a pathogenic mechanism for the development of GN involving a novel podocyte-neutrophil axis and reveal the importance of glomerular NF-κB inhibition by the ubiquitin binding …
Il-1Β Amplification Of Nitric Oxide Production And Its Inhibitory Effects On Glucose Induced Early Growth Response-1 Expression In Ins-1 Cells, Ada Young
Electronic Theses and Dissertations
The pathophysiology of cytokines released by infiltrating white blood cells upon pancreatic beta cells is not fully understood. Early growth response gene-1 (Egr-1) expression is specifically and transiently up regulated in pancreatic beta cells in response to glucose. We hypothesized that interleukin-1 beta (IL-1▀) induction of nitric oxide alters glucose induced Egr-1 transcription levels. Egr-1 levels were assessed via western blot, nitric oxide was measured with a Griess Reagent kit and insulin levels via ELISA. Glucose induced both insulin and Egr-1 production in INS-1 cells. IL-1▀ dose dependently increased nitric oxide production over time and significantly attenuated glucose induced Egr-1 …
Prelamin A Influences A Program Of Gene Expression In Regulation Of Cell Cycle Control, Christina N. Bridges
Prelamin A Influences A Program Of Gene Expression In Regulation Of Cell Cycle Control, Christina N. Bridges
Electronic Theses and Dissertations
The A-type lamins are intermediate filament proteins that constitute a major part of the eukaryotic nuclear lamina—a tough, polymerized, mesh lining of the inner nuclear membrane, providing shape and structural integrity to the nucleus. Lamin A (LA) filaments also permeate the nucleoplasm, providing additional structural support, but also scaffolding numerous tethered molecules to stabilize, organize, and facilitate molecular interactions to accomplish critical functions of cellular metabolism. Over the past 2 decades, much attention has been focused on roles of LA in maintenance of nuclear structural integrity. Only since the late 1990s have scientists discovered the devastating effects of LA gene …