Medicine and Health Sciences Commons^™

Rnai Therapeutics In Autoimmune Disease, Kaleb M. Pauley, Seunghee Cha

Science and Mathematics Faculty Publications

Since the discovery of RNA interference (RNAi), excitement has grown over its potential therapeutic uses. Targeting RNAi pathways provides a powerful tool to change biological processes post-transcriptionally in various health conditions such as cancer or autoimmune diseases. Optimum design of shRNA, siRNA, and miRNA enhances stability and specificity of RNAi-based approaches whereas it has to reduce or prevent undesirable immune responses or off-target effects. Recent advances in understanding pathogenesis of autoimmune diseases have allowed application of these tools in vitro as well as in vivo with some degree of success. Further research on the design and delivery of effectors of …

Autoantibodies Against Muscarinic Type 3 Receptor In Sjögren's Syndrome Inhibit Aquaporin 5 Trafficking, B. Lee, A. E. Gauna, G. Perez, Y. Park, Kaleb M. Pauley, Toshihisa Kawai, Seunghee Cha

Science and Mathematics Faculty Publications

Sjo¨gren’s syndrome (SjS) is a chronic autoimmune disease that mainly targets the salivary and lacrimal glands. It has been controversial whether anti-muscarinic type 3 receptor (a-M3R) autoantibodies in patients with SjS inhibit intracellular trafficking of aquaporin-5 (AQP5), water transport protein, leading to secretory dysfunction. To address this issue, GFPtagged human AQP5 was overexpressed in human salivary gland cells (HSG-hAQP5) and monitored AQP5 trafficking to the plasma membrane following carbachol (CCh, M3R agonist) stimulation. AQP5 trafficking was indeed mediated by M3R stimulation, shown in partial blockage of trafficking by M3R-antagonist 4-DAMP. HSG-hAQP5 pre-incubated with SjS plasma for 24 hours significantly reduced …

Presence Of Porphyromonas Gingivalis In Gingival Squamous Cell Carcinoma, J. Katz, M. Onate, Kaleb M. Pauley, I Bhattacharyya, S. Cha

Science and Mathematics Faculty Publications

Periodontal disease has been recently linked to a variety of systemic conditions such as diabetes, cardiovascular disease, preterm delivery, and oral cancer. The most common bacteria associated with periodontal disease, Porphyromonas gingivalis (P. gingivalis) has not yet been studied in the malignant gingival tissues. The objective of this study was to investigate the presence of P. gingivalis in specimens from squamous cell carcinoma patients. We have performed immunohistochemical staining to investigate the presence of P. gingivalis and Streptococcus gordonii (S. gordonii), a non invasive oral bacteria, in paraffin embedded samples of gingival squamous cell carcinoma (n=10) and …

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 …

Upregulated Mir-146a Expression In Peripheral Blood Mononuclear Cells From Rheumatoid Arthritis Patients, Kaleb M. Pauley, M. Satoh, A. L. Chan, M. R. Bubb, W. H. Reeves, E. K. Chan

Science and Mathematics Faculty Publications

Introduction

MicroRNAs are small noncoding RNA molecules that negatively regulate gene expression via degradation or translational repression of their targeted mRNAs. It is known that aberrant microRNA expression can play important roles in cancer, but the role of microRNAs in autoimmune diseases is only beginning to emerge. In this study, the expression of selected microRNAs is examined in rheumatoid arthritis.

Methods

Total RNA was isolated from peripheral blood mononuclear cells obtained from patients with rheumatoid arthritis, and healthy and disease control individuals, and the expression of miR-146a, miR-155, miR-132, miR-16, and microRNA let-7a was analyzed using quantitative real-time PCR.

Results …

Bioinformatics In The 21st Century, Heather G. Kuruvilla

Science and Mathematics Faculty Publications

No abstract provided.

Detection Of The Argonaute Protein Ago2 And Micrornas In The Rna Induced Silencing Complex (Risc) Using A Monoclonal Antibody, K. Ikeda, M. Satoh, Kaleb M. Pauley, M. J. Fritzler, W. H. Reeves, E. K. Chan

Science and Mathematics Faculty Publications

MicroRNAs (miRNAs) are short RNA molecules responsible for post-transcriptional gene silencing by the degradation or translational inhibition of their target messenger RNAs (mRNAs). This process of gene silencing, known as RNA interference (RNAi), is mediated by highly conserved Argonaute (Ago) proteins which are the key components of the RNA induced silencing complex (RISC). In humans, Ago2 is responsible for the endonuclease cleavage of targeted mRNA and it interacts with the mRNAbinding protein GW182, which is a marker for cytoplasmic foci referred to as GW bodies (GWBs). We demonstrated that the antiAgo2 monoclonal antibody 4F9 recognized GWBs in a cell cycle …