Cell Biology Commons^™

The Role Of B Cell Activation State And Sex In Aryl Hydrocarbon Receptor Mediated Induction Of Chemokine Receptor 9 And Alpha4beta7 Expression In Vitro, Logan Bauerle

Master's Theses

Defense of mucosal tissues from microbial infection and allergy is reliant on continual production of antibodies. The aryl hydrocarbon receptor (AhR) is known to regulate B cell development and is associated with suppression of systemic humoral immunity. Recent attention has been paid to the role of the AhR in altering expression of cell adhesion molecules (CAMs). B cells express CAMs and chemokine receptors to migrate around the body for localized secretion of antibodies. AhR agonists promote B cell migration to the small intestine through upregulation of chemokine receptor 9 (CCR9) and integrin α₄β₇. Both the AhR …

Investigating Optimal Laboratory Growth Conditions Of Gracilibacillus Halotolerans In Media Supplemented With Salt, Isaac Young

Annual Research Symposium

As interest continues to grow in the field of persister cells and their morphology, there arises an ever-evolving desire to further understand specific strains of bacteria that exemplify the qualities of seemingly anomalous survival regardless of anti-bacterial treatment. In the case of the Gracilibacillus halotolerans, a halotolerant extremophile extracted from the Great Salt Lake with known persistent characteristics, uncovering its optimal growth conditions was essential for future investigations. Identifying the optimal salinity for the growth of G. halotolerans will allow us to standardize our growth methods, uncover several mechanisms of saline tolerance, and add to future investigations of persistence with …

Characterization Of The Effects Of The Pyrazolopyrimidine Inhibitor Grassofermata (Nav-2729) In The Eukaryotic Pathogen Trypanosoma Brucei, Kristina Marie Parman

All Dissertations

The protozoan pathogen, Trypanosoma brucei, is the causative agent of sleeping sickness in humans and nagana in livestock in sub-Saharan Africa. T. brucei cycles between tsetse fly and mammalian hosts, and it is adapted to survive in diverse host tissues. Variant Surface Glycoprotein (VSG) plays a key role in immune evasion in the mammalian host. The VSG membrane anchor requires two myristates, 14-carbon saturated fatty acids (FAs) that are scarce in the host. T. brucei can synthesize FAs de novo, but also readily takes up exogenous FAs, despite lacking homologs to fatty acid uptake proteins found in other …

Cellular Mechanism Of Pentagalloyl Gucose-Mediated Prevention And Reversal Of Abdominal Aortic Aneurysms, Greg Halsey

All Dissertations

Abdominal aortic aneurysm (AAA) has been the 15th leading cause of death in persons older than 55 for the past ten years in several Western countries, with rupture resulting in an almost 100% mortality rate. AAA is a focal dilation of the aorta characterized by progressive loss of elastin and vascular smooth muscle cells (SMCs), as well as persistent inflammatory response [1]. The only treatment for AAA is surgery; however, the mortality post-procedure is still 1-4%, with a 15-30% chance of morbidity [2].

Pentagalloyl glucose (PGG) treatment is effective in the reversal of AAA. While its stabilizing interactions with extracellular …

Modified Vaccine Vectors To Understand Adjuvant Functions Of Listeria During Chronic Schistosomiasis, Stephanie K. Norwood

Biological Sciences Theses & Dissertations

Vaccination is one of the most effective strategies employed to prevent infectious diseases. Successful vaccination is dependent upon the induction of a specific, robust, and prolonged immune response. One of the major challenges faced by vaccine development is vaccine failure due to host-related factors that can modulate the immune system, which leads to non-responsiveness to vaccinations. The generation of new vaccine strategies is imperative to combat these effects. Live bacterial vectors are one approach used as they can elicit humoral immunity, cellular immunity, or both. Listeria monocytogenes is a Gram positive, intracellular pathogen that is an effective bacterial vaccine vector …

Immunepotent Crp Enhances Cyclophosphamide-Induced Cytotoxicity Through A Caspase Independent But Ros Dependent Mechanism In Triple Negative-Breast Cancer Cells, Ana L. Rivera, A. C. Martínez-Torres, C. Rodríguez-Padilla

Research Symposium

Background: Breast cancer (BC) is one of the leading causes of cancer death worldwide. Cyclophosphamide (CYP) remains a mainstay in cancer therapy mainly in the triple negative breast cancer subtype (TNBC) in spite of harmful adverse effects and cell death-resistances. To face this, combination of chemotherapies and immunotherapies has been proposed. IMMUNEPOTENT CRP (ICRP) is an immunotherapy that has cytotoxic effects in several cancer cells without affecting peripheral blood mononuclear cells (PBMC) and CD3+ cells, beside improving clinical parameters of chemotherapy-treated patients. The aim of this study was to evaluate the mechanism of cytotoxicity induced by ICRP in combination with …

Endothelial Interleukin-17 Receptor D (Il17rd) Promotes Western Diet-Induced Aortic Myeloid Cell Infiltration, Shivangi Pande

Electronic Theses and Dissertations

The Interleukin-17 (IL17) family is a group of cytokines implicated in the etiology of several inflammatory diseases. Interleukin-17 receptor D (IL17RD), also known as Sef (similar expression to fibroblast growth factor), belonging to the family of IL17 receptors, has been shown to modulate IL17A-associated inflammatory phenotypes. The objective of this study was to test the hypothesis that IL17RD promotes endothelial cell activation and consequent monocyte adhesion. We utilized primary human aortic endothelial cells and demonstrated that RNAi targeting of IL17RD suppressed transcript levels by 83% compared to non-targeted controls. Further, RNAi knockdown of IL17RD decreased the adhesion of THP-1 cells …

Investigating The Role Of Il-10 Producing Nkt Cells In Prevention Of Graft Versus Host Disease, Drew Boagni

Dissertations & Theses (Open Access)

The standard curative treatment for hematologic malignancies is allogeneic stem cell transplantation (ASCT), in which the patient’s immune system is replaced with that of a healthy donor. This can lead to cure through the graft versus leukemia (GVL) effect but can also cause graft versus host disease (GVHD), which is characterized by systemic inflammation and organ damage mediated by dysregulated donor T cells. Preclinical studies have shown invariant natural killer T cells (iNKT) cells can prevent GVHD while preserving GVL. iNKT cells are unconventional T cells which recognize glycolipid antigens presented in the context of CD1d. Upon activation, they secrete …

Elucidating The Biomechanics Of Mertk-Mediated Efferocytosis, Brandon Hayato Dickson

Electronic Thesis and Dissertation Repository

Macrophages are key mediators of efferocytosis – the phagocytic engulfment and removal of apoptotic cells. During engulfment, the coordinated activity of efferocytic receptors induces the remodeling of the actin cytoskeleton, which facilitates the envelopment of the cell by the plasma membrane. Mer receptor tyrosine kinase (MERTK) is a crucial efferocytic receptor, but its role during actin remodeling is not well understood. Previously, our lab showed that MERTK is an activator of β₂ integrins – which are comprised of receptors known to induce the actin polymerization that is required for engulfment. We hypothesized that MERTK is an indirect stimulator of …

Development Of Wiskott-Aldrich Syndrome Knock Out Protocol For Drug Substance Assay Development, Julia C. Hanna

Master's Theses

Wiskott-Aldrich Syndrome (WAS) is a rare X-linked primary immunodeficiency affecting approximately 1 in 100,000 live XY births in North America and is caused by a mutation to the WAS gene which is expressed across hematopoietic lineages. The WAS protein (WASp) plays a role in regulating actin polymerization. On a cellular level, there are a variety of effects of a lack of WASp or expression of a dysfunctional WASp protein for patients including issues with migration, adhesion, chemotactic response, phagocytosis, activation, and proliferation across different cell types in addition to reduced platelet size and output. This can lead to several systematic …

Immunomodulatory Effects Of Resolvin D2 In A Model Of Infection, Prem Yugandhar Kadiyam Sundarasivarao

Graduate School of Biomedical Sciences Theses and Dissertations

Dysregulated hyperinflammatory host immune response to underlying bacterial infections is a characteristic of sepsis. In sepsis, bacteria often trigger abnormal hyperinflammatory responses which can cause multiple organ failure and if sustained can lead to an immunosuppressive phase where the host is susceptible to secondary infections caused by opportunistic bacteria like Pseudomonas aeruginosa (P. aeruginosa). In our studies, we used a 2-hit model of cecal ligation and puncture (CLP) followed by P. aeruginosa secondary lung infection to investigate cellular and molecular mechanisms in the beneficial action of resolvin D2 (RvD2). Resolvins of the D-series are a group of fatty acids known …

Adipocytes And Innate Immunity In Systemic Sclerosis, Nancy Wareing

Dissertations & Theses (Open Access)

Systemic sclerosis (SSc; scleroderma) is a chronic systemic autoimmune and connective tissue disorder characterized by vasculopathy, autoimmune phenomena, and widespread fibrosis. Skin thickening and tightening is the cardinal feature of SSc and is responsible, in part, for the considerable morbidity of this disease. There are currently no targeted treatments for skin manifestations in SSc, primarily due to our fragmented understanding of its pathophysiologic mechanisms. In PART I, we report a previously unappreciated link between aberrant expression of the developmental gene sine oculis homeobox homolog 1 (SIX1) in skin-associated adipocytes in SSc skin and the early loss of dermal white adipose …

The Effects Of Specialized Pro-Resolving Mediator Lipoxin A4 On Pseudomonas Aeruginosa Biofilms And Interactions With Monocytes, Julianne M. Thornton

Graduate School of Biomedical Sciences Theses and Dissertations

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen known as a major cause of hospital-acquired secondary infections, commonly causing chronic respiratory infections in immunocompromised individuals, especially those with cystic fibrosis, and often found in wound infections. P. aeruginosa uses the quorum sensing pathway to readily form protective biofilms, which reduce the efficacy of antibiotics and access by host immune cells to eradicate the pathogen. Specialized pro-resolving mediators (SPMs) are lipids endogenously produced by the host immune response to infection to aid in infection resolution. One SPM, Lipoxin A4 (LxA4), has been shown to be a robust quorum sensing inhibitor.

The …

Investigating The Antibacterial And Immunomodulatory Properties Of Lactobacillus Acidophilus Postbiotics, Rachael M. Wilson

Graduate School of Biomedical Sciences Theses and Dissertations

Probiotics are nonpathogenic microorganisms that have been extensively studied for their ability to prevent various infectious, gastrointestinal, and autoimmune diseases. The mechanisms underlying these probiotic effects have not been elucidated. However, we and other researchers have evidence suggesting that probiotic bacteria secrete metabolites that are antimicrobial and anti-inflammatory. As such, we developed a methodology to collect the secreted metabolites from a probiotic bacterium, Lactobacillus acidophilus, and tested this cell free filtrate (CFF) both in vitro and in vivo. Using this CFF, we have demonstrated that L. acidophilus secretes a molecule(s) that has specific bactericidal activity against the opportunistic pathogen, Pseudomonas …

Mirna-489 Induces Immunogenic Cell Death In Triple Negative Breast Cancer Cells, Ryan P. Titus

Senior Theses

It has been well established that microRNAs (miRNAs) play an important role in the regulation of gene expression and consequently promoting or downregulating molecular pathways. When dysregulated, miRNAs have been found to serve as important biomarkers for cancer diagnosis and influence tumor initiation and progression. It has been previously established that miRNA-489 is a tumor suppressor microRNA, and it directly targets cell proliferative pathways like the HER2-SHP2-MAPK pathway. In this study, we focus on the role of miRNA-489, in the induction of immunogenic cell death (ICD) in triple-negative breast cancer cell lines. We first examined the effects of miRNA-489 on …

The Role Of Schwann Cells In Nerve Injury: Forskolin-Mediated Camp Activation Upregulates Tnfα Expression Despite Nf-Κb Downregulation In Lps-Treated Schwann Cells, Caitlyn E. Henry, Angela L. Asirvatham Ph.D.

Student Research Poster Presentations 2023

Although Schwann cells are known to play a role in axonal regeneration following nerve injury and inflammation, the exact mechanism is unknown. This study explores two potential mechanisms: the NF-κB and cAMP pathways. The NF-κB pathway produces cytokines, such as TNFα, to regulate inflammation, whereas the cAMP pathway is anti-inflammatory and regulates Schwann cell proliferation via AKAP95 and cyclin D3. Although it is well-known that NF-κB and cAMP are involved in inflammation, not much is known regarding the effects of forskolin-mediated cAMP activation on LPS-mediated NF-κB activation in Schwann cells. In this study, RT4-D6P2T immortalized rat Schwann cells were treated …

Sex-Dependent Effects Of Induced Acute Inflammation On Glucose Homeostasis And Rna Editing Enzymes, Christian A. Rivas

MSU Graduate Theses

The first line of defense against bodily insults, like pathogen invasion, is the innate immune system. Innate immunity sets in motion countless cascades that result in inflammation. Inflammation simultaneously affects multiple biological processes like metabolism and gene expression. Males and females react differently to inflammation. To understand both molecular and physiological sex differences in inflammation, we examined how inflammation affects gene expression and glucose metabolism. Adenosine deaminase acting on RNA (ADAR1) is upregulated by inflammation and catalyzes RNA editing, a process where nucleotides encoded by the genome are modified. ADAR1 also controls the innate immune reaction by decreasing activity of …

Proposing An Rna Interference (Rnai)-Based Treatment For Human Immunodeficiency Virus (Hiv) By Analyzing The Post-Transcriptional Gene Targeting Of Sars-Cov-2, Hepatitis C Virus, And A549 Lung Cancer Cells, Arjun Jagdeesh

Undergraduate Research Posters

Human Immunodeficiency Virus (HIV) is a retrovirus that infects CD4+ T cell lymphocytes in humans, leading to the development of Acquired Immunodeficiency Syndrome (AIDS) if left untreated. While current treatment methods, including antiretroviral combination treatments, effectively limit HIV replication, HIV can evade these treatments due to its high mutation rate. Long-term antiretroviral treatment can also be toxic to patients, meaning patients would benefit from a new mechanism of HIV treatment. RNA interference (RNAi) is an antiviral pathway found in mammals, plants, and insects that involves a small-interfering RNA that is incorporated into a protein complex called the RNA-induced Silencing Complex …

Dna Methylation And The Response To Infection In Introduced House Sparrows, Melanie Gibson

Electronic Theses and Dissertations

Epigenetics is the study of molecular modification of a genome without changing its base pairs. The most studied type of epigenetic mechanism is DNA methylation, which is capable of turning a gene “on” or “off.” Epigenetic potential is the capacity to which an individual can have methylation on its genome. The more CpGs available, the greater the epigenetic potential. In invasive species, genetic variation has been observed to be paradoxical: not much of it exists on a genomic level, but epigenetically, phenotypic variation can occur. The focus on shift in gene expression in this study is on Toll-Like Receptor 4 …

Evaluation Of Leishmanicidal Activities Of 4-Thiazolidinones Against Leishmania Major, The Causative Agent Of Human Cutaneous Leishmaniasis, Kiera Bush

All Master's Theses

The leishmaniases are a group of vector-borne parasitic diseases that affect many developing countries including parts of Africa, India, and the Middle East in addition to Southern Europe and the Americas. It is estimated that worldwide, there are about 3 million new cases of leishmaniases each year leading to as many as 50,000 fatalities annually. The parasites that cause leishmaniasis belong to the genus Leishmania spp and are transmitted by the female phlebotomine sand fly. There are three clinical forms of the infection: visceral, mucocutaneous, and cutaneous. However, the focus of this paper is on cutaneous leishmaniasis that causes skin …

A Novel Transmembrane Ligand Inhibits T Cell Receptor Activation, Yujie Ye

Doctoral Dissertations

T lymphocytes (T cells) play essential roles in the adaptive immune system. Each mature T cell expresses one type of functional T cell receptor (TCR). The TCR recognizes antigens bound to the major histocompatibility complex (MHC) in antigen presenting cells. The resulting stimulation signal crosses the transmembrane domain of TCR and initiates downstream signaling cascades. The human immune system relies on TCRs to recognize a variety of pathogens. Normally, TCR can distinguish the self-antigens from pathogenic antigens. However, dysfunction or aberrant expression of TCRs causes different inflammatory and autoimmune diseases, which afflict millions of people annually (Chapter I). Current treatments …

Function Of Atm And Msh2 During Dna Repair And Recombination, Emily Sible

Dissertations, Theses, and Capstone Projects

Class switch recombination (CSR) produces secondary immunoglobulin isotypes and requires AID-dependent DNA deamination of intronic switch (S) regions within the immunoglobulin heavy chain (Igh) gene locus. Non-canonical repair of deaminated DNA by mismatch repair (MMR) or base excision repair (BER) creates DNA breaks that permit recombination between distal S regions. ATM-dependent phosphorylation of AID at serine-38 (pS38-AID) promotes its interaction with APE1, a BER protein, suggesting that ATM regulates CSR through BER. However, pS38-AID may also function in MMR during CSR, although the mechanism remains unknown. To examine whether ATM modulates BER- and/or MMR-dependent CSR, Atm^-/- mice …

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

Dissertations & 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) …

Resolving The Repression Pathway Of Virulence Gene Hila In Salmonella, Alexandra King, Lon Chubiz Phd, Brenda Pratte, Lauren Daugherty

Undergraduate Research Symposium

Salmonella is a relatively abundant, virulent species of bacteria that is most known for spreading gastrointestinal diseases through food. These illnesses result in approximately 1.35 million infections, including over 25,000 hospitalizations each year, in the U.S. alone (CDC.gov). As antibiotic resistance becomes an increasingly urgent public health problem, the importance of developing alternative treatment methods is only becoming more crucial. One of the genes responsible for this virulence is known as hilA. HilA is the main transcriptional regulator of Salmonella Pathogenicity Island-1 gene (UniProt). SPI-1 plays an important role in the invasion of Salmonella into epithelial cells. The proteins encoded …

Structural Formation And Functionality Of The Spoiie Protein In Clostridium Difficile, Rachel Siebenmorgen

Biological Sciences Undergraduate Honors Theses

My research efforts were directed toward the structure and functionality of a protein, designated SpoIIE [11], which previously has been shown to regulate C. difficile peptide utilization in addition to sporulation and toxin release. The SpoIIE protein is found in all spore-forming gram-positive bacteria and is a crucial component in activation of transcription factors and septum formation thus affecting the regulation and timing of spore development [11,12]. A truncated form of the SpoIIE protein named SpoIIE∆TM was used in an effort to determine the structure of an important but uncharacterized linker domain of the protein. If the structure and specific …

Feasibility Of Tubulin As A Control For Gene Expression Following Transfection In Mouse Monocyte/Macrophage-Like Cells, Ankita Chabra

Honors Program Theses and Research Projects

Transfection, which is the ability to modify host cells’ genetic content, has broad application in studying normal cellular processes, molecular mechanism of disease and gene therapy. There are several transfection techniques, and all require either a control or a reference gene. Commonly used controls for transfection experiments are housekeeping genes, which maintain expression for a given cell/tissue, experimental conditions, and treatment. However, recent research has uncovered that expression levels of housekeeping genes may vary depending on the gene, cell type and experimental conditions. A growing body of evidence demonstrates that housekeeping genes are inadequate internal standards for measuring gene expression …

Salicylic Acid And N-Hydroxypipecolic Acid At The Fulcrum Of The Plant Immunity-Growth Equilibrium, Alyssa Shields, Vanessa Shivnauth, Christian Danve M. Castroverde

Biology Faculty Publications

Salicylic acid (SA) and N-hydroxypipecolic acid (NHP) are two central plant immune signals involved in both resistance at local sites of pathogen infection (basal resistance) and at distal uninfected sites after primary infection (systemic acquired resistance). Major discoveries and advances have led to deeper understanding of their biosynthesis and signaling during plant defense responses. In addition to their well-defined roles in immunity, recent research is emerging on their direct mechanistic impacts on plant growth and development. In this review, we will first provide an overview of how SA and NHP regulate local and systemic immune responses in plants. We …

Determining The Role Of Dendritic Cells During Response To Treatment With Paclitaxel/Anti-Tim-3, Alycia Gardner

USF Tampa Graduate Theses and Dissertations

Intratumoral CD103+ dendritic cells (cDC1) are required for anti-tumor immune responses. In tumors that are poorly responsive to immunotherapeutic approaches targeting T cells, targeting cDC1 represents an alternative approach that may be useful in improving patient response rates. As such, it is critical to understand cDC1 function within tumors, and what may be preventing optimal function of cDC1. TIM-3 is a receptor that is highly expressed by cDC1 in murine and human mammary tumors, and TIM-3 blocking antibodies are currently being evaluated in clinical trials for a number of solid and hematological malignancies. In order to best design combinatorial therapeutic …

Cell-Engineered Vesicles For Therapeutic Delivery And Immunomodulatory Applications, Khaga Neupane

Theses and Dissertations--Chemistry

Development of a new kind of drug delivery system (DDS) that could efficiently deliver therapeutics to the cell of interest would allow us to accomplish cell-specific drug delivery while eliminating systemic toxicity. Although nanocarriers including endogenously released extracellular vesicles (EEVs), liposomes, and small molecules seem to be promising drug delivery systems, biological challenges persist for their use in clinical applications. Here, we demonstrate nanovesicles engineered by fragmenting cellular membranes can be exploited as versatile DDSs for therapeutics delivery as well as immunomodulatory functions. Cell-engineered vesicles were produced by cavitating cells using nitrogen gas at high pressure followed by serial centrifugation. …

Bone Morphogenetic Proteins Shape TReg Cells, Piotr Kraj

Biological Sciences Faculty Publications

The transforming growth factor-β (TGF-β) family includes cytokines controlling cell behavior, differentiation and homeostasis of various tissues including components of the immune system. Despite well recognized importance of TGF-β in controlling T cell functions, the immunomodulatory roles of many other members of the TGF-β cytokine family, especially bone morphogenetic proteins (BMPs), start to emerge. Bone Morphogenic Protein Receptor 1α (BMPR1α) is upregulated by activated effector and Foxp3+ regulatory CD4+ T cells (Treg cells) and modulates functions of both of these cell types. BMPR1α inhibits generation of proinflammatory Th17 cells and sustains peripheral Treg cells. This finding underscores the importance of …