Immunology and Infectious Disease Commons^™

Micrornas Associated With Melanoma Inflammation And Response To Pd-1 Inhibition, Robert Szczepaniak Sloane

Dissertations & Theses (Open Access)

Melanoma is an aggressive malignancy of melanocytes with historically poor outcomes. Melanoma therapy has improved markedly over the past decade with advances in molecularly targeted agents and immunotherapies. Immune checkpoint inhibitors achieve T-cell mediated anti-tumor efficacy by blocking engagement of inhibitory checkpoints on T-cells to overcome immunosuppressive signals from tumor cells and the broader microenvironment. Despite these advances, there are a significant proportion of patients who do not benefit from existing immunotherapy strategies making it a priority to identify and target the mechanisms that confer resistance to therapy. We demonstrate that microRNAs are accurate markers of microenvironment composition with prognostic …

Deciphering The Micrornaome In Hiv Associated Lung Comorbidities, Rajib Kumar Dutta

FIU Electronic Theses and Dissertations

Chronic Respiratory diseases like chronic obstructive pulmonary disease (COPD), pulmonary hypertension, asthma, and pneumonia are emerging as significant comorbidities in people living with HIV in the combination antiretroviral therapy (cART) era. HIV is an independent risk factor for these diseases independent of tobacco smoke, and cigarette smoking exacerbates outcomes in HIV patients. Both tobacco smoke and HIV infection suppress nasal mucociliary clearance (MCC) as well as bronchial MCC, a primary innate defense mechanism in the airway. Optimal MCC depends on airway surface liquid (ASL) lining the airway epithelium that facilitates ciliary beating to clear the mucus. Attenuation of any component …

Canonical Notch Signaling Positively Regulates Mir-155 Transcription In A Nfκb-Dependent Manner, Joe Torres

Doctoral Dissertations

MicroRNA-155 (miR-155) is an important pro-inflammatory molecule that controls immune responses in both physiological and pathological settings. Although miR-155 is well studied, little is known about its transcriptional regulation in T cells. We sought to further understand the mechanisms by which miR-155 transcription is induced following T cell activation. We found that miR-155 transcription is dependent on the activity of the Notch and NFkB signaling pathways. It was determined that the canonical Notch signaling pathway was involved in this regulation and that it was dependent upon the activation of NFkB. Additional work confirmed that both NFkB and Notch1 directly bind …

Notch1 Modification And Signaling In T Helper Cell Differentiation, Karthik Chandiran

Doctoral Dissertations

Notch signaling modulates the developmental program of multiple cell types. The cleaved intracellular region of the receptor possess the functional domain which influences T cell activation, proliferation and differentiation. However, in naïve CD4 T cells the mechanistic details underlying cleavage of Notch1 is not clearly understood. Notch functions by acting as a signaling hub and interacting with its canonical (CSL) and non-canonical (NFkB, mTOR, Akt) binding partners to cross-talk with other signaling pathways. Notch signaling drives the differentiation program of multiple T helper cell subsets (Th1, Th2, Th17, Th9, iTreg and TFH). Recent discoveries also demonstrated a role for microRNAs …

Migration Frustrations Of Mir-146a Regulation, Emma Baccus, Victoria Gahman, Hannah Phillips, Shannon Rappaport, Alyssa Reiter, Kaleb M. Pauley

The Research and Scholarship Symposium (2013-2019)

The autoimmune disease, Sjögren’s Syndrome (SS), causes the degradation of salivary and lacrimal glands due to an influx of immune cells. In previous studies, a significant increase in miR-146a was observed in the peripheral blood mononuclear cells of SS patients. Since immune cell infiltration is critical in SS pathogenesis, the following research examines the effect of miR-146a on cell migration. We hypothesize that transfecting THP-1 human monocytes with synthetic miR-146a will downregulate migration of the monocytes based on other studies stating that miR-146a downregulates migration in vivo. In order to execute our experiment, we transfected THP-1 cells with synthetic miR-146a …

Effect Of Metformin On Mir-146a Expression, S. Jackson Grout, Bryce C. Macturk, Amanda D. Sims, Kaleb M. Pauley

The Research and Scholarship Symposium (2013-2019)

Sjögren’s Syndrome (SjS) is an autoimmune disorder that affects secretory glands in the human body, restricting their function and causing extreme dryness in areas like the mouth and eyes. miR-146a is an anti-inflammatory microRNA that targets the NFκB activation pathway. Previous studies have shown that SjS patients have increased miR-146a expression, despite having high levels of inflammation. The objective of this study was to investigate whether metformin, a diabetes drug with a wide variety of effects and potential functions, reduces levels of miR-146a expression. Metformin is known to reduce inflammation by inhibiting the activation of NFκB. THP-1 human monocytes were …

Mir-146a Upregulation Of Phagocytosis In Human Macrophages, Ryan Marquardt, Daniel J. Stank, Kaleb M. Pauley

The Research and Scholarship Symposium (2013-2019)

Sjögrens Syndrome (SjS) is an autoimmune disease that attacks exocrine glands such as salivary and lacrimal glands resulting in severe dryness of the mouth and eyes. Previous studies have linked increased microRNA-146a (miR-146a) expression in peripheral blood mononuclear cells in SjS patients compared to healthy controls. MicroRNAs (miRNAs), small non-coding RNA molecules that post-transcriptionally regulate gene expression, are known to play key regulatory roles in immune responses and have been implicated in a growing number of autoimmune disorders. Further investigation into the role of increased miR-146a expression in SjS revealed links to several immune functions including phagocytosis.Our goal was to …

A Novel Molecular Relationship Between Parn And Pld That, When Deregulated, Contributes To The Aggressive Phenotype Of Breast Cancer Cell Lines., Taylor Elaine Miller

Browse all Theses and Dissertations

The removal of mRNA transcript poly(A) tails by 3'-5' exonucleases is the rate-limiting step for controlled mRNA decay in eukaryotes. Poly(A)-specific ribonuclease (PARN) is one such exonuclease that degrades poly(A) tails, and although its in vitro activity is well-characterized, PARN’s patho-physiological roles in the cell are not well understood. Prior studies have found a possible role for PARN in cancer, in that PARN expression levels in human breast cancer tissues are often decreased compared to normal control tissues. Indeed, data mined from the ONCOMINE cancer array database showed that PARN is downregulated in patient invasive breast carcinoma samples compared to …

Dnp63a Suppresses Cell Invasion By Targeting Rac1 Through Mir-320a, Amjad Ahmed Aljagthmi

Browse all Theses and Dissertations

DNp63a, a member of the p53 family of transcription factors, is overexpressed in a number of cancers and known to play a role in proliferation, differentiation, migration and invasion. DNp63a has been shown to regulate several microRNAs that play a role in both development and cancer, but to date there has not been a global analysis of p63- regulated miRNA. Using next-generation sequencing of small RNA from wild type and sip63 transfected HaCaT cells, our laboratory recently identified a number of DNp63a- regulated miRNAs by RNA-Seq studies which may serve as biomarkers of cancer progression. We identified a novel miRNA, …

Endothelial Hspa12b Is A Novel Protein For The Preservation Of Cardiovascular Function In Polymicrobial Sepsis Via Exosome Mir-126, Xia Zhang

Electronic Theses and Dissertations

Sepsis is the most frequent cause of mortality in most intensive care units. Cardiovascular dysfunction is a major complication associated with sepsis, with high mortality rates up to 70%. Currently, there is no effective treatment approach for sepsis.

The integrity of the endothelium is fundamental for the homeostasis of the cardiovascular system. Sepsis induces endothelial cell injury which is the key factor for multiple organ failure. The increased expression of adhesion molecules and chemokines in endothelial cell promotes leukocytes infiltration into the tissue. The loss of tight junction proteins and increased permeability of the endothelial cells will provoke tissue hypoxia …

Optimization Of Fluorescent Phagocytic Assay Using Apoptotic Cells, Jacob L. Brown, Jason R. Leigh, Ryan Marquardt, Cambria R. Puffenberger, Daniel J. Stank, Kaleb M. Pauley

The Research and Scholarship Symposium (2013-2019)

Sjögren’s Syndrome is a systemic autoimmune disease that primarily affects the exocrine glands and is characterized by severe dry eyes and mouth. Previous studies have shown that there are elevated levels of the microRNA miR-146a in Sjögren’s patients. Mir-146a is a microRNA that has been found to be involved in down regulating inflammation. Yet, in patients with Sjögren’s Syndrome, there is a large upregulation of miR-146a that exists alongside chronic inflammation. This led us to investigate the role of miR-146a in Sjögren’s Syndrome. We found that miR-146a upregulates phagocytosis of E. coli by human macrophages. Therefore, we hypothesized that this …

Delineating ΔNp63α'S Function In Epithelial Cells, Suraj Sakaram

Browse all Theses and Dissertations

ΔNp63α, the most physiologically relevant isoform of p63, a p53 family member protein, maintains the proliferative capacity of the basal layer of epithelial tissues and is highly expressed in non-melanoma skin cancer. It has been implicated in a variety of different cancers, including breast, lung, and prostate cancers, however the complex role it plays in disease remains poorly understood. Elucidating ΔNp63α’s regulatory network may provide insight into its role in epithelial tissues and in cancer progression. The objective of this thesis is to investigate ΔNp63α’s upstream regulation in the context of non-melanoma skin cancer as well as expand on ΔNp63α’s …

Contribution Of Micrornas And Robo4 Signaling After Herpes Simplex Virus Infection: Role For Regulatory Mechanisms, Sachin Vishvas Mulik

Doctoral Dissertations

Herpes simplex virus (HSV) infection of the eye results in chronic immunopathological response in corneal stroma orchestrated by CD4 T cells. Due to its neurotrophic nature, HSV can also invade brain and leads to deadly encephalitis. HSV infection of the eyes leads to corneal neovascularization (CV), which is an important step in the pathogenesis of herpetic stromal keratitis (HSK), an important cause of human blindness. This study was undertaken to investigate the contribution of miRNAs and Robo4 signaling in HSK. The role of miR-132 and miR-155 was evaluated. In the first chapter, we review literature regarding the contribution of miRNAs …

Microrna In Autoimmunity And Autoimmune Diseases, Kaleb M. Pauley, S. Cha, E. K. Chan

Science and Mathematics Faculty Publications

MicroRNAs (miRNAs) are small conserved non-coding RNA molecules that post-transcriptionally regulate gene expression by targeting the 3′ untranslated region (UTR) of specific messenger RNAs (mRNAs) for degradation or translational repression. miRNA-mediated gene regulation is critical for normal cellular functions such as the cell cycle, differentiation, and apoptosis, and as much as one-third of human mRNAs may be miRNA targets. Emerging evidence has demonstrated that miRNAs play a vital role in the regulation of immunological functions and the prevention of autoimmunity. Here we review the many newly discovered roles of miRNA regulation in immune functions and in the development of autoimmunity …