Immunopathology Commons^™

Cluster Homolog Of Immunoglobulin-Like Receptor Genes In Chicken Immune Responses, Brandi A. Sparling

Graduate Theses, Dissertations, and Problem Reports (ETD)

This dissertation explores the identity and role of immunoglobulin-like (Ig-like) receptors in chickens, with focus on their implications in disease and disease progression. These receptors, wisely expressed across immune cells, interact with the major histocompatibility complex (MHC) class I molecules to modulate immune responses in mammals. Due to the insufficient representation of chicken Ig-like receptors in online databases, this study systematically annotates the chicken Cluster Homolog of Immunoglobulin-like Receptors (CHIR) genes using advanced bioinformatic techniques, aligning with the release of the 7th edition of the chicken genome assembly that comprises builds for a broiler and layer chicken. The analysis identifies …

Vitamin D Enhanced Vitamin D Receptor (Vdr) Inhibition Of Nlrp3 Inflammasome Activation Can Attenuate The Development Of Autoimmune Thyroiditis, Alexzon Mandac

Capstone Showcase

Autoimmune Thyroiditis (AIT) is a prevalent autoimmune disease affecting approximately 2% of the population. Characterized by the gradual loss of thyroid function through an autoimmune attack on the thyroid gland, the disease manifests symptoms that negatively affect one’s quality of life. The mechanisms behind the disease’s pathophysiology are not fully understood; however, researchers are examining the involvement of the NLRP3 inflammasome in the disease. This thesis will address the question of whether Vitamin D can act as an inhibitor of the NLRP3 inflammasome and attenuate the progression of AIT in mouse model. Current investigations explore the effects of NLRP3 inhibition …

Growth And Differentiation Factor 15 (Gdf15) Levels Predict Adverse Respiratory Outcomes In Premature Neonates, Faeq Almudares, Joseph Hagan, Xinpu Chen, Sridevi Devaraj, Bhagavatula Moorthy, Krithika Lingappan

Faculty, Staff and Students Publications

Growth and differentiation factor 15 (GDF15) is a stress-responsive cytokine, and its expression increases during inflammation, hyperoxia, and senescence. Significantly, GDF15 is secreted by the placenta, and maternal levels increase throughout pregnancy. Serum GDF15 level is a promising biomarker for many lung diseases like pulmonary hypertension and pulmonary fibrosis. However, circulating GDF15 levels in preterm infants and their role as a predictor of respiratory outcomes have not been studied. We hypothesized that GDF15 levels would increase with gestational age at birth, and that postnatal GDF15 will be correlated with adverse respiratory outcomes in preterm infants. Scavenged blood samples were retrieved …

Resident Education And Virtual Medicine: A Faculty Development Session To Enhance Trainee Skills In The Realm Of Telemedicine, Anna E Rueda, Ana C Monterrey, Margaret Wood, Linessa Zuniga, Betty Del Rio Rodriguez

Faculty, Staff and Students Publications

INTRODUCTION: COVID-19 accelerated the use of telemedicine. Subsequently, clinical sites began conducting virtual visits. Academic institutions implemented telemedicine for patient care and simultaneously had to teach residents the logistics and best practices. To meet this need, we developed a training session for faculty focused on telemedicine best practices and teaching telemedicine in the pediatric realm.

METHODS: We designed this training session based on institutional and society guidelines and faculty experience with telemedicine. Objectives included telemedicine documentation, triage, counseling, and ethical issues in telemedicine. We conducted all sessions in a 60-minute or 90-minute format over a virtual platform for small and …

Lox Upregulates Fak Phosphorylation To Promote Metastasis In Osteosarcoma, Xiang Chen, Margaret Clement, M John Hicks, Poonam Sarkar, M Waleed Gaber, Tsz-Kwong Man

Faculty, Staff and Students Publications

Osteosarcoma is a malignant bone tumor that commonly occurs in the pediatric population. Despite the use of chemotherapy and surgery, metastasis remains to be the leading cause of death in patients with osteosarcoma. We have previously reported that cytoplasmic mislocalization of p27 is associated with a poor outcome in osteosarcoma. In this study, we further show that lysyl oxidase (LOX) expression was associated with p27 mislocalization. LOX is an enigmatic molecule that acts as a tumor suppressor or a metastatic promoter; however, its role in osteosarcoma is still unclear. Hence, we performed both

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

Graduate Theses/Dissertations

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 …

Proximity-Dependent Biotin Labeling In Testicular Germ Cells Identified Tesmin-Associated Proteins, Seiya Oura, Akinori Ninomiya, Fuminori Sugihara, Martin M Matzuk, Masahito Ikawa

Faculty, Staff and Students Publications

Characterization of protein-protein interactions (PPI) is a key to understanding the functions of proteins of interest. Recently developed proximity-dependent biotin identification (BioID) has been actively investigated as an alternative PPI mapping method because of its usefulness in uncovering transient PPI. Here, as an example of proximity labeling proteomics application in the testis, we generated two transgenic mouse lines expressing two biotin ligases (BioID2 or TurboID) fused with TESMIN, which translocates from the cytosol to the nucleus during meiotic progression and is required for reproduction. The BioID2 transgene, albeit not the TurboID transgene, rescued fertility defects of the Tesmin KO male …

Single Cell Rna Sequencing Of The Adult Drosophila Eye Reveals Distinct Clusters And Novel Marker Genes For All Major Cell Types, Kelvin Yeung, Komal Kumar Bollepogu Raja, Yoon-Kyung Shim, Yumei Li, Rui Chen, Graeme Mardon

Faculty, Staff and Students Publications

The adult Drosophila eye is a powerful model system for phototransduction and neurodegeneration research. However, single cell resolution transcriptomic data are lacking for this tissue. We present single cell RNA-seq data on 1-day male and female, 3-day and 7-day old male adult eyes, covering early to mature adult eyes. All major cell types, including photoreceptors, cone and pigment cells in the adult eye were captured and identified. Our data sets identified novel cell type specific marker genes, some of which were validated in vivo. R7 and R8 photoreceptors form clusters that reflect their specific Rhodopsin expression and the specific Rhodopsin …

Clinical And Molecular Insights Into Gastrointestinal Dysfunction In Myotonic Dystrophy Types 1 & 2, Janel A M Peterson, Thomas A Cooper

Faculty, Staff and Students Publications

Myotonic dystrophy (DM) is a highly variable, multisystemic disorder that clinically affects one in 8000 individuals. While research has predominantly focused on the symptoms and pathological mechanisms affecting striated muscle and brain, DM patient surveys have identified a high prevalence for gastrointestinal (GI) symptoms amongst affected individuals. Clinical studies have identified chronic and progressive dysfunction of the esophagus, stomach, liver and gallbladder, small and large intestine, and rectum and anal sphincters. Despite the high incidence of GI dysmotility in DM, little is known regarding the pathological mechanisms leading to GI dysfunction. In this review, we summarize results from clinical and …

Depletion Of Cd206+ M2-Like Macrophages Induces Fibro-Adipogenic Progenitors Activation And Muscle Regeneration, Allah Nawaz, Muhammad Bilal, Shiho Fujisaka, Tomonobu Kado, Muhammad Rahil Aslam, Saeed Ahmed, Keisuke Okabe, Yoshiko Igarashi, Yoshiyuki Watanabe, Takahide Kuwano, Koichi Tsuneyama, Ayumi Nishimura, Yasuhiro Nishida, Seiji Yamamoto, Masakiyo Sasahara, Johji Imura, Hisashi Mori, Martin M Matzuk, Fujimi Kudo, Ichiro Manabe, Akiyoshi Uezumi, Takashi Nakagawa, Yumiko Oishi, Kazuyuki Tobe

Faculty, Staff and Students Publications

Muscle regeneration requires the coordination of muscle stem cells, mesenchymal fibro-adipogenic progenitors (FAPs), and macrophages. How macrophages regulate the paracrine secretion of FAPs during the recovery process remains elusive. Herein, we systemically investigated the communication between CD206+ M2-like macrophages and FAPs during the recovery process using a transgenic mouse model. Depletion of CD206+ M2-like macrophages or deletion of CD206+ M2-like macrophages-specific TGF-β1 gene induces myogenesis and muscle regeneration. We show that depletion of CD206+ M2-like macrophages activates FAPs and activated FAPs secrete follistatin, a promyogenic factor, thereby boosting the recovery process. Conversely, deletion of the FAP-specific follistatin gene results in …

Role Of Cd38 In Pulmonary Host Defense Against Gram-Negative Pneumonia, Xiaoqian Shan

LSU Master's Theses

The Gram-negative bacterium, Klebsiella pneumoniae, is a major cause of hospital-acquired pneumonia in the U.S. In particular, the dramatic increase in carbapenem-resistant K. pneumoniae infections poses a serious threat to the public health both in the United States and worldwide. Clearance of bacteria in the lungs depends on effective pulmonary immune response. It may be possible to design improved therapies that augment host immune responses while attenuating excessive pulmonary inflammation through modulation of key innate immunity molecules during pneumonic infections. Cluster differentiation CD38 (CD38) has been detected on the surface of many immune cells or intracellular compartments, acting as …

Validation Of Atovaquone Plasma Levels By Liquid Chromatography-Tandem Mass Spectrometry For Therapeutic Drug Monitoring In Pediatric Patients, Thomas D Horvath, Izmarie Poventud-Fuentes, Lily Olayinka, Asha James, Sigmund J Haidacher, Kathleen M Hoch, Alexandra M Stevens, Anthony M Haag, Sridevi Devaraj

Faculty, Staff and Students Publications

BACKGROUND: Atovaquone has traditionally been used as an antiparasitic and antifungal agent, but recent studies have shown its potential as an anticancer agent. The high variability in atovaquone bioavailability highlights the need for therapeutic drug monitoring, especially in pediatric patients. The goal of our study was to develop and validate the performance of an assay to quantify atovaquone plasma concentrations collected from pediatric cancer patients using LC-MS/MS.

METHODS: Atovaquone was extracted from a 10 µL volume of K

RESULTS: Atovaquone and its deuterated internal standard were analyzed using a gradient chromatographic method that had an overall cycle-time of 7.4 min …

Clinical And Molecular Features Of Pediatric Cancer Patients With Lynch Syndrome, Sarah Scollon, Mohammad K Eldomery, Jacquelyn Reuther, Frank Y Lin, Samara L Potter, Lauren Desrosiers, Kenneth L Mcclain, Valeria Smith, Jack Meng-Fen Su, Rajkumar Venkatramani, Jianhong Hu, Viktoriya Korchina, Neda Zarrin-Khameh, Richard A Gibbs, Donna M Muzny, Christine Eng, Angshumoy Roy, D Williams Parsons, Sharon E Plon

Faculty, Staff and Students Publications

BACKGROUND: The association of childhood cancer with Lynch syndrome is not established compared with the significant pediatric cancer risk in recessive constitutional mismatch repair deficiency syndrome (CMMRD).

PROCEDURE: We describe the clinical features, germline analysis, and tumor genomic profiling of patients with Lynch syndrome among patients enrolled in pediatric cancer genomic studies.

RESULTS: There were six of 773 (0.8%) pediatric patients with solid tumors identified with Lynch syndrome, defined as a germline heterozygous pathogenic variant in one of the mismatch repair (MMR) genes (three with MSH6, two with MLH1, and one with MSH2). Tumor analysis demonstrated evidence for somatic second …

Spatial Profiling Of The Prostate Cancer Tumor Microenvironment Reveals Multiple Differences In Gene Expression And Correlation With Recurrence Risk, Vinay Kumar, Pavneet Randhawa, Robert Bilodeau, Dan Mercola, Michael Mcclelland, Anshu Agrawal, James Nguyen, Patricia Castro, Michael M Ittmann, Farah Rahmatpanah

Faculty, Staff and Students Publications

The tumor microenvironment plays a crucial role in both the development and progression of prostate cancer. Furthermore, identifying protein and gene expression differences between different regions is valuable for treatment development. We applied Digital Spatial Profiling multiplex analysis to formalin-fixed paraffin embedded prostatectomy tissue blocks to investigate protein and transcriptome differences between tumor, tumor-adjacent stroma (TAS), CD45+ tumor, and CD45+ TAS tissue. Differential expression of an immunology/oncology protein panel (n = 58) was measured. OX40L and CTLA4 were expressed at higher levels while 22 other proteins, including CD11c, were expressed at lower levels (FDR < 0.2 and p-value < 0.05) in TAS as compared to tumor epithelia. A tissue microarray analysis of 97 patients with 1547 cores found positive correlations between high expression of CD11c and increased time to recurrence in tumor and TAS, and inverse relationships for CTLA4 and OX40L, where higher expression in tumor correlated with lower time to recurrence, but higher time to recurrence in TAS. Spatial transcriptomic analysis using a Cancer Transcriptome Atlas panel (n = 1825 genes) identified 162 genes downregulated and 69 upregulated in TAS versus tumor, 26 downregulated and 6 upregulated in CD45+ TAS versus CD45+ tumor. We utilized CIBERSORTx to estimate the relative immune cell fractions using CD45+ gene expression and found higher average fractions for memory B, naïve B, and T cells in TAS. In summary, the combination of protein expression differences, immune cell fractions, and correlations of protein expression with time to recurrence suggest that closely examining the tumor microenvironment provides valuable data that can improve prognostication and treatment techniques.

A Study Of Multiple Sclerosis, Christine Chen

The Cardinal Edge

No abstract provided.

Rolling Stones: An Instructive Case Of Neonatal Cholestasis, Paige Killelea, Shruti Sakhuja, Jose Hernandez, M John Hicks, Sanjiv Harpavat

Faculty, Staff and Students Publications

BACKGROUND: Jaundice within the first 1-2 weeks of a neonate's life will generally self-resolve; however, if it lasts longer than this time frame it warrants further work up. Direct or conjugated hyperbilirubinemia can suggest neonatal cholestasis, which in turn reflects marked reduction in bile secretion and flow. The differential diagnosis for neonatal cholestasis is broad. Neonatal choledocholithiasis is a rare cause of neonatal cholestasis, but should be considered on the differential diagnosis for patients presenting with elevated conjugated bilirubin.

CASE PRESENTATION: We describe an infant who presented with neonatal cholestasis. He subsequently underwent work up for biliary atresia, as this …

Prenatal Choline Supplementation During Maternal Obesity Alters Offspring Response To Western Diets, Hunter W. Korsmo

Dissertations, Theses, and Capstone Projects

Maternal obesity has led to an increase in adverse offspring developmental outcomes and a greater risk for long-term metabolic diseases. Choline, a semi-essential nutrient, can be incorporated into phosphatidylcholine (PC) as well as sphingomyelin (SM) and donate its labile methyl group for the remethylation of homocysteine after choline is oxidized to betaine. Prenatal choline insufficiency has been related to maternal obesity and metabolic diseases, such as metabolic associated fatty liver disease (MAFLD). Choline may interact with maternal obesity to influence the programming offspring.

Chapter 1 presents an introduction of choline and the various clinical outcomes associated with choline supplementation during …

Factors Associated With Severe Illness In Patients Aged <21 Years Hospitalized For Covid-19, Rewa Choudhary, Bryant J Webber, Lindsay S Womack, Hannah K Dupont, Sophia K Chiu, Valentine Wanga, Megan E Gerdes, Sophia Hsu, Dallas S Shi, Theresa M Dulski, Osatohamwen I Idubor, Arthur M Wendel, Nickolas T Agathis, Kristi Anderson, Tricia Boyles, Eleanor S Click, Juliana Da Silva, Mary E Evans, Jeremy A W Gold, Julia C Haston, Pamela Logan, Susan A Maloney, Marisol Martinez, Pavithra Natarajan, Kevin B Spicer, Mark Swancutt, Valerie A Stevens, Jessica Rogers-Brown, Gyan Chandra, Megan Light, Frederick E Barr, Jessica Snowden, Larry K Kociolek, Matthew Mchugh, David L Wessel, Joelle N Simpson, Kathleen C Gorman, Kristen A Breslin, Roberta L Debiasi, Aaron Thompson, Mark W Kline, Julie A Boom, Ila R Singh, Michael Dowlin, Mark Wietecha, Beth Schweitzer, Sapna Bamrah Morris, Emilia H Koumans, Jean Y Ko, David A Siegel, Anne A Kimball

Faculty, Staff and Students Publications

OBJECTIVES: To describe coronavirus disease 2019 (COVID-19)-related pediatric hospitalizations during a period of B.1.617.2 (Δ) variant predominance and to determine age-specific factors associated with severe illness.

METHODS: We abstracted data from medical charts to conduct a cross-sectional study of patients agedchildren's hospitals from July to August 2021 for COVID-19 or with an incidental positive severe acute respiratory syndrome coronavirus 2 test. Among patients with COVID-19, we assessed factors associated with severe illness by calculating age-stratified prevalence ratios (PR). We defined severe illness as receiving high-flow nasal cannula, positive airway pressure, or invasive mechanical ventilation.

RESULTS: Of 947 hospitalized patients, 759 …

Effectiveness And Safety Of Immunosuppressants And Biological Therapy For Chronic Spontaneous Urticaria: A Network Meta-Analysis, Wen-Kuang Lin, Shwu-Jiuan Lin, Woan-Ruoh Lee, Chia-Chieh Lin, Weei-Chin Lin, Hua-Ching Chang, Chi-Tsun Cheng, Jason C Hsu

Faculty, Staff and Students Publications

Chronic spontaneous urticaria (CSU) is the most common phenotype of chronic urticaria. We compared treatment effects and safety profiles of the medications in patients with CSU. We searched PubMed, MEDLINE, and Web of Science for randomized control trials (RCTs), from 1 January 2000 to 31 July 2021, which evaluated omalizumab and immunosuppressants. Network meta-analyses (NMAs) were performed with a frequentist approach. Outcome assessments considered the efficacy (Dermatology Life Quality Index (DLQI) and weekly urticaria activity score (UAS7)) and tolerability profiles with evaluations of study quality, inconsistencies, and heterogeneity. We identified 14 studies which we included in our direct and indirect …

Mrnip Interacts With Sex Body Chromatin To Support Meiotic Progression, Spermatogenesis, And Male Fertility In Mice, Samina Kazi, Julio M Castañeda, Audrey Savolainen, Yiding Xu, Ning Liu, Huanyu Qiao, Ramiro Ramirez-Solis, Kaori Nozawa, Zhifeng Yu, Martin M Matzuk, Renata Prunskaite-Hyyryläinen

Faculty, Staff and Students Publications

Meiosis has a principal role in sexual reproduction to generate haploid gametes in both sexes. During meiosis, the cell nucleus hosts a dynamic environment where some genes are transcriptionally activated, and some are inactivated at the same time. This becomes possible through subnuclear compartmentalization. The sex body, sequestering X and Y chromosomes during male meiosis and creating an environment for the meiotic sex chromosome inactivation (MSCI) is one of the best known and studied subnuclear compartments. Herein, we show that MRNIP forms droplet‐like accumulations that fuse together to create a distinct subnuclear compartment that partially overlaps with the sex body …