Medical Immunology Commons^™

Floxed-Cassette Allelic Exchange Mutagenesis Enables Markerless Gene Deletion In Chlamydia Trachomatis And Can Reverse Cassette-Induced Polar Effects, Gabrielle Keb, Robert Hayman, Kenneth A. Fields

Microbiology, Immunology, and Molecular Genetics Faculty Publications

As obligate intracellular bacteria, Chlamydia spp. have evolved numerous, likely intricate, mechanisms to create and maintain a privileged intracellular niche. Recent progress in elucidating and characterizing these processes has been bolstered by the development of techniques enabling basic genetic tractability. Florescence-reported allelic exchange mutagenesis (FRAEM) couples chromosomal gene deletion with the insertion of a selection cassette encoding antibiotic resistance and green fluorescent protein (GFP). Similar to other bacteria, many chlamydial genes exist within polycistronic operons, raising the possibility of polar effects mediated by insertion cassettes. Indeed, FRAEM-mediated deletion of Chlamydia trachomatis tmeA negatively impacts the expression of tmeB. We …

Intratumoral Sting Activation Sensitizes Poorly Immunogenic Cancers To Checkpoint Blockade Immunotherapy, Casey Ager

Dissertations and Theses (Open Access)

Unprecedented durable tumor regression can be achieved in patients with checkpoint blockade immunotherapy, yet these responses are rare and are not observed in all tumor types. Castration resistant prostate cancer (CRPC) and pancreatic adenocarcinoma (PDAC) are two common lethal cancers that remain refractory to checkpoint blockade, requiring development of new therapeutic approaches to promote responsivity in patients with these diseases. Both CRPC and PDAC are characterized by an immunosuppressive tumor milieu rich in cells of the myeloid lineage, which regulate T cell activity in many ways independent of the coinhibitory receptor axis. We investigated whether activation of acute inflammatory signaling …

A Virus-Encoded Type I Interferon Decoy Receptor Enables Evasion Of Host Immunity Through Cell-Surface Binding., Bruno Hernáez, Juan Manuel Alonso-Lobo, Imma Montanuy, Cornelius Fischer, Sascha Sauer, Luis J. Sigal, Noemí Sevilla, Antonio Alcamí

Department of Microbiology and Immunology Faculty Papers

Soluble cytokine decoy receptors are potent immune modulatory reagents with therapeutic applications. Some virus-encoded secreted cytokine receptors interact with glycosaminoglycans expressed at the cell surface, but the biological significance of this activity in vivo is poorly understood. Here, we show the type I interferon binding protein (IFNα/βBP) encoded by vaccinia and ectromelia viruses requires of this cell binding activity to confer full virulence to these viruses and to retain immunomodulatory activity. Expression of a variant form of the IFNα/βBP that inhibits IFN activity, but does not interact with cell surface glycosaminoglycans, results in highly attenuated viruses with a virulence similar …

Development Of Onchocerca Volvulus In Humanized Nsg Mice And Detection Of Parasite Biomarkers In Urine And Serum., John B. Patton, Sasisekhar Bennuru, Mark L. Eberhard, Jessica A. Hess Ligas, April R. Torigian, Sara Lustigman, Thomas B. Nutman, David Abraham

Department of Microbiology and Immunology Faculty Papers

BACKGROUND: The study of Onchocerca volvulus has been limited by its host range, with only humans and non-human primates shown to be susceptible to the full life cycle infection. Small animal models that support the development of adult parasites have not been identified.

METHODOLOGY/PRINCIPAL FINDINGS: We hypothesized that highly immunodeficient NSG mice would support the survival and maturation of O. volvulus and alteration of the host microenvironment through the addition of various human cells and tissues would further enhance the level of parasite maturation. NSG mice were humanized with: (1) umbilical cord derived CD34+ stem cells, (2) fetal derived liver, …

Roles Of Cytosolic Nucleic Acid Sensors In Cancer And Infection, Qifan Zhu

Theses and Dissertations (ETD)

Pattern recognition receptors are innate immune sensors that recognize pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) with crucial roles in host defense against microbial infection, autoimmune diseases and cancer. Cytosolic nucleic acids including DNA and RNA originate from pathogens or self-cells, which form major groups of PAMPs and DAMPs. A range of nucleic acid sensors have evolved to sense various types of nucleic acids. How different DNA-sensing pathways regulate microbial infection and cancer is the focus of this dissertation.

Stimulator of IFN genes (STING) is a cytosolic innate immune sensor for cyclic dinucleotides that also serves a dual …

Distinct Role Of Il-27 In Immature And Lps-Induced Mature Dendritic Cell-Mediated Development Of Cd4, Fang Zhou, Guang-Xian Zhang, A. M. Rostami

Department of Neurology Faculty Papers

Interleukin-27 (IL-27) plays an important role in regulation of anti-inflammatory responses and autoimmunity; however, the molecular mechanisms of IL-27 in modulation of immune tolerance and autoimmunity have not been fully elucidated. Dendritic cells (DCs) play a central role in regulating immune responses mediated by innate and adaptive immune systems, but regulatory mechanisms of DCs in CD4⁺ T cell-mediated immune responses have not yet been elucidated. Here we show that IL-27 treated mature DCs induced by LPS inhibit immune tolerance mediated by LPS-stimulated DCs. IL-27 treatment facilitates development of the CD4⁺ CD127⁺3G11⁺ regulatory T cell subset …

Development Of A Pd-L1 Pet Imaging Biomarker, Caleb Jack Bridgwater

Posters-at-the-Capitol

Immunotherapy strategies are very promising treatments for cancer patients. Specifically, Immune checkpoint inhibitor therapy focusing on the PD-1/PD-L1 pathway shows long-lasting positive results in many cancer patients. Unfortunately, not all the patients can benefit from this highly effective treatment. Hence, there is a great need for predictive biomarkers. Immunohistochemical (IHC) staining has been used as a way of predicting patient response, yet shows many problems. For example, IHC utilizes an invasive biopsy and sample fixing, which creates an incomplete and delayed picture of the patient’s biochemistry and the tumor microenvironment, consequently ignoring metastases.

The purpose of this study is to …

Kaposi’S Sarcoma-Associated Herpesvirus Seropositivity Is Associated With Type 2 Diabetes Mellitus: A Case–Control Study In Xinjiang, China, Meng Cui, Qiwen Fang, Jun Zheng, Zhanjun Shu, Yin Chen, Yage Fan, Juan Zhao, Charles Wood, Tiejun Zhang, Yan Zeng

Nebraska Center for Virology: Faculty Publications

Objective: To assess the potential relationship between Kaposi’s sarcoma-associated herpesvirus (KSHV) infection and type 2 diabetes mellitus (DM-2) in Xinjiang, China.

Methods: A case–control study of consecutively included DM-2 patients and normal controls was conducted among the Uygur and Han populations in Xinjiang Uygur Autonomous Region, China. Blood samples were collected and KSHV seroprevalence, antibody titers, and viral load were investigated. Logistic regression analysis and multiple linear regression analysis were applied to explore determinants of the main outcome measures.

Results: A total of 324 patients with DM-2 and 376 normal controls were included. The seroprevalence of KSHV was 49.1% (95% …

Stress-Induced Heat Shock Protein 40 And Immune Function In Altered Gravity, Amber M. Paul, Brooke D. Shepard, Sharmila Bhattacharya

Publications

In space, astronauts are more susceptible to pathogens, viral reactivation and immunosuppression, which poses limits to their health and the mission. Interestingly, during space flight, stress-inducible heat shock proteins (HSP) are robustly induced, and the overexpression of HSPs have been implicated in immune dysregulation, therefore HSPs may be critically involved in regulating immune homeostasis. HSP40/DNAJ1 plays a major role in proper protein translation and folding. Its loss of function has been implicated in susceptibility to microbial infection, while its overexpression has been implicated in autoimmunity, collectively suggesting its complicated, but necessary, role in maintaining immunological function. To determine the role …

Gene Gangs Of The Chloroviruses: Conserved Clusters Of Collinear Monocistronic Genes, Phillip Seitzer, Adrien Jeanniard, Fangrui Ma, James L. Van Etten, Marc T. Facciotti, David D. Dunigan

Nebraska Center for Virology: Faculty Publications

Chloroviruses (family Phycodnaviridae) are dsDNA viruses found throughout the world’s inland waters. The open reading frames in the genomes of 41 sequenced chloroviruses (330 + 40 kbp each) representing three virus types were analyzed for evidence of evolutionarily conserved local genomic “contexts”, the organization of biological information into units of a scale larger than a gene. Despite a general loss of synteny between virus types, we informatically detected a highly conserved genomic context defined by groups of three or more genes that we have termed “gene gangs”. Unlike previously described local genomic contexts, the definition of gene gangs requires only …

Antibody Epitope Specificity For Dsdna Phosphate Backbone Is An Intrinsic Property Of The Heavy Chain Variable Germline Gene Segment Used, Tatjana Srdic-Rajic, Heinz Kohler, Vladimir Jurisic, Radmila Metlas

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Analysis of protein sequences by the informational spectrum method (ISM) enables characterization of their specificity according to encoded information represented with defined frequency (F). Our previous data showed that F(0.367) is characteristic for variable heavy chain (VH) domains (a combination of variable (V), diversity (D) and joining (J) gene segments) of the anti-phosphocholine (PC) T15 antibodies and mostly dependent on the CDR2 region, a site for PC phosphate group binding. Because the T15 dsDNA-reactive U4 mutant also encodes F(0.367), we hypothesized that the same frequency may also be characteristic for anti-DNA antibodies. Data obtained from an analysis of 60 spontaneously …

Role Of The Fractalkine Receptor In Cns Autoimmune Inflammation: New Approach Utilizing A Mouse Model Expressing The Human Cx3cr1, Sandra M. Cardona, Sangwon V. Kim, Kaira A. Church, Vanessa O. Torres, Ian A. Cleary, Andrew S. Mendiola, Stephen P. Saville, Stephanie S. Watowich, Jan Parker-Thornburg, Alejandro Soto-Ospina, Pedronel Araque, Richard M. Ransohoff, Astrid E. Cardona

Department of Microbiology and Immunology Faculty Papers

Multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS) is the leading cause of non-traumatic neurological disability in young adults. Immune mediated destruction of myelin and oligodendrocytes is considered the primary pathology of MS, but progressive axonal loss is the major cause of neurological disability. In an effort to understand microglia function during CNS inflammation, our laboratory focuses on the fractalkine/CX3CR1 signaling as a regulator of microglia neurotoxicity in various models of neurodegeneration. Fractalkine (FKN) is a transmembrane chemokine expressed in the CNS by neurons and signals through its unique receptor CX3CR1 present in microglia. During …

Polymicrobial Sepsis Influences Nk-Cell-Mediated Immunity By Diminishing Nk-Cell-Intrinsic Receptor-Mediated Effector Responses To Viral Ligands Or Infections., Isaac J. Jensen, Christina S. Winborn, Micaela G. Fosdick, Peng Shao, Mikaela M. Tremblay, Qiang Shan, Sandeep Kumar Tripathy, Christopher M. Snyder, Hai-Hui Xue, Thomas S. Griffith, Jon C. Houtman, Vladimir P. Badovinac

Department of Microbiology and Immunology Faculty Papers

The sepsis-induced cytokine storm leads to severe lymphopenia and reduced effector capacity of remaining/surviving cells. This results in a prolonged state of immunoparalysis, that contributes to enhanced morbidity/mortality of sepsis survivors upon secondary infection. The impact of sepsis on several lymphoid subsets has been characterized, yet its impact on NK-cells remains underappreciated-despite their critical role in controlling infection(s). Here, we observed numerical loss of NK-cells in multiple tissues after cecal-ligation-and-puncture (CLP)-induced sepsis. To elucidate the sepsis-induced lesions in surviving NK-cells, transcriptional profiles were evaluated and indicated changes consistent with impaired effector functionality. A corresponding deficit in NK-cell capacity to produce …

Susceptibility Genes To Plant Viruses, Hernan Garcia-Ruiz

Nebraska Center for Virology: Faculty Publications

Plant viruses use cellular factors and resources to replicate and move. Plants respond to viral infection by several mechanisms, including innate immunity, autophagy, and gene silencing, that viruses must evade or suppress. Thus, the establishment of infection is genetically determined by the availability of host factors necessary for virus replication and movement and by the balance between plant defense and viral suppression of defense responses. Host factors may have antiviral or proviral activities. Proviral factors condition susceptibility to viruses by participating in processes essential to the virus. Here, we review current advances in the identification and characterization of host factors …

The Conquest Of Pus -- A History Of Bitumen, Creosote And Carbolic Acid, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

In the Western world from antiquity on, open wounds were treated topically with petroleum-derived substances, such as bitumen, asphalt, pitch, and tar. The immediate aim was to stifle bleeding and ease pain but a potential benefit was preventing local corruption with pus formation. In the early 19th century, creosote was recovered from bitumen and found to reduce suppuration. Carbolic acid was later isolated from creosote and recognized as an underlying active agent. In the 1860s, carbolic acid was first employed by Jules Lemaire to treat local skin infections and later by Joseph Lister to prevent the suppuration in compound fractures. …

Pathogenicity And Protection Mediated By A Single Tcrβ In Experimental Autoimmune Encephalomyelitis, Tianhua Wu

Theses and Dissertations (ETD)

How the TCR repertoire, together with risk-associated major histocompatibility complex (MHC), imposes susceptibility for autoimmune disease is not fully understood. A small fraction of TCR α or β chains are “public”, and are shared by most individuals.High-throughput sequencing of the mouse TCRβ repertoire during myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmuneencephalomyelitis (EAE) identified a public TCRβ chain, TCRβ1, which was highly shared among individual mice and preferentially deployed during EAE. Retrogenic expression of TCRβ1 resulted in spontaneous early-onset EAE in mice with high penetrance and severity, despite being paired with a diverse endogenous TCRα repertoire. To further study autoimmunity conferred by …

Atherosclerosis In Subjects Newly Diagnosed With Human Immunodeficiency Virus Infection., Tatiana V Kirichenko, Veronika A Myasoedova, Tatiana E Shimonova, Alexandra A Melnichenko, Dmitri Sviridov, Igor A Sobenin, Alexey I Mazus, Alexander N Orekhov, Michael I Bukrinsky

Microbiology, Immunology, and Tropical Medicine Faculty Publications

HIV infection is associated with the increased risk of cardiovascular disease (CVD), even in patients successfully treated with the combination antiretroviral therapy (cART). However, the relationship between HIV, cART, and pathogenesis of CVD remains controversial. In the present study, we evaluated the carotid intima-media thickness (CIMT), a surrogate marker of atherosclerosis, in HIV-infected subjects receiving or not receiving cART. One hundred nine newly diagnosed HIV-infected subjects and one hundred nine uninfected age-matched controls (all males) without the history of CVD, hypertension, or diabetes were recruited into the present study. Cross-sectional analysis at baseline (BL) showed significantly increased levels of triglycerides …

Transcriptomic Insights On The Virulence-Controlling Csra, Badr, Rpon, And Rpos Regulatory Networks In The Lyme Disease Spirochete, William K. Arnold, Christina R. Savage, Kathryn G. Lethbridge, Trever C. Smith, Catherine A. Brisette, Janakiram Seshu, Brian Stevenson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Borrelia burgdorferi, the causative agent of Lyme disease, survives in nature through a cycle that alternates between ticks and vertebrates. To facilitate this defined lifestyle, B. burgdorferi has evolved a gene regulatory network that ensures transmission between those hosts, along with specific adaptations to niches within each host. Several regulatory proteins are known to be essential for the bacterium to complete these critical tasks, but interactions between regulators had not previously been investigated in detail, due to experimental uses of different strain backgrounds and growth conditions. To address that deficit in knowledge, the transcriptomic impacts of four critical …

Carnosol Modulates Th17 Cell Differentiation And Microglial Switch In Experimental Autoimmune Encephalomyelitis, Xing Li, Li Zhao, Juan-Juan Han, Fei Zhang, Shuai Liu, Lin Zhu, Zhe-Zhi Wang, Guang-Xian Zhang, Yuan Zhang

Department of Neurology Faculty Papers

Medicinal plants as a rich pool for developing novel small molecule therapeutic medicine have been used for thousands of years. Carnosol as a bioactive diterpene compound originated from Rosmarinus officinalis (Rosemary) and Salvia officinalis, herbs extensively applied in traditional medicine for the treatment of multiple autoimmune diseases (1). In this study, we investigated the therapeutic effects and molecule mechanism of carnosol in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Carnosol treatment significantly alleviated clinical development in the myelin oligodendrocyte glycoprotein (MOG35–55) peptide-induced EAE model, markedly decreased inflammatory cell infiltration into the central nervous system and reduced …

Combination Oral Immunotherapy With Il-10 And Il-12 Effectively Treats Colon Tumors Via Synergistic Effects On Il-17 Producing T Cells And Colon Epithelial Barrier Integrity., Neal Bhutiani

Electronic Theses and Dissertations

In this dissertation, the relationship between colon cancer and inflammation, the utility of novel imaging modalities for diagnosis of colitis and cancer, and the therapeutic efficacy of orally delivered, particle-based immunotherapy for the treatment of colon cancer are evaluated. In Chapters One and Two, multispectral optoacoustic tomography (MSOT) is demonstrated to effectively detect colon inflammation without the use of exogenous contrast prior to detection using conventional colonoscopy. Oral particle uptake is demonstrated in the distal small intestine and proximal colon, confirming site-specific delivery. In Chapter Three, administration of IL-10 and IL-12 containing particles is shown to act synergistically to significantly …

Endomembrane-Associated Pre-Embedding Immunogold Labeling, Zuzana Nichtova, Celia Fernandez-Sanz, A. Bartok, Sergio De La Fuente, György Hajnóczky, Shey-Shing Sheu, György Csordás

Department of Pathology, Anatomy, and Cell Biology Posters

Aim

To optimize the pre-embedding IG in stable cell lines and primary adult cardiomyocytes to get the most effective visualization of endomembrane/associated proteins: endo/sarcoplasmic reticulum Ca2+ release channels IP3 receptors and ryanodine receptors (IP3R, and RyR2) and the mitochondrial fission protein Drp1.

With Some Risk-Taking And Luck: A Veterinarian's Adventures In Viral Immunology., Luis J. Sigal

Department of Microbiology and Immunology Faculty Papers

No abstract provided.

Regulations Of Pathogenic Cd4+ T Helper Lymphocytes In Inflammatory Diseases, Handong Zheng

Biomedical Sciences ETDs

In this comprehensive project, three interrelated studies with distinct foci were employed to understand the regulations of specific CD4⁺ T helper cell population in inflammatory diseases.

Pathogenic TH17 cells play an essential role in the initiation and development of both human multiple sclerosis (MS) and animal experimental autoimmune encephalomyelitis (EAE). Nevertheless, the underlying mechanism by which the pathogenicity of TH17 cells is controlled in the autoimmune neuro-inflammation remains unclear. In aim 1, we revealed that lumican (Lum), an extracellular matrix (ECM) protein, negatively regulates encephalitic TH17 cell responses. Our findings highlighted a TH17 cell-intrinsic effect of Lum in suppressing …

Novel Role Of Prostate Apoptosis Response-4 Tumor Suppressor In B-Cell Chronic Lymphocytic Leukemia, Mary Kathryn Mckenna, Sunil K. Noothi, Sara S. Alhakeem, Karine Z. Oben, Joseph T. Greene, Rajeswaran Mani, Kathryn L. Perry, James P. Collard, Jacqueline R. Rivas, Gerhard C. Hildebrandt, Roger A. Fleischman, Eric B. Durbin, John C. Byrd, Chi Wang, Natarajan Muthusamy, Vivek M. Rangnekar, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Prostate apoptosis response-4 (Par-4), a proapoptotic tumor suppressor protein, is downregulated in many cancers including renal cell carcinoma, glioblastoma, endometrial, and breast cancer. Par-4 induces apoptosis selectively in various types of cancer cells but not normal cells. We found that chronic lymphocytic leukemia (CLL) cells from human patients and from Eµ-Tcl1 mice constitutively express Par-4 in greater amounts than normal B-1 or B-2 cells. Interestingly, knockdown of Par-4 in human CLL-derived Mec-1 cells results in a robust increase in p21/WAF1 expression and decreased growth due to delayed G1-to-S cell-cycle transition. Lack of Par-4 also increased the expression of p21 and …

Chronic Lymphocytic Leukemia-Derived Il-10 Suppresses Antitumor Immunity., Sara S Alhakeem, Mary K Mckenna, Karine Z Oben, Sunil K Noothi, Jacqueline R Rivas, Gerhard C Hildebrandt, Roger A Fleischman, Vivek M Rangnekar, Natarajan Muthusamy, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Chronic lymphocytic leukemia (CLL) patients progressively develop an immunosuppressive state. CLL patients have more plasma IL-10, an anti-inflammatory cytokine, than healthy controls. In vitro human CLL cells produce IL-10 in response to BCR cross-linking. We used the transgenic Eμ-T cell leukemia oncogene-1 (

Tgf-Β Sustains Tumor Progression Through Biochemical And Mechanical Signal Transduction., Robert L Furler, Douglas F Nixon, Christine A Brantner, Anastas Popratiloff, Christel H Uittenbogaart

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Transforming growth factor β (TGF-β) signaling transduces immunosuppressive biochemical and mechanical signals in the tumor microenvironment. In addition to canonical SMAD transcription factor signaling, TGF-β can promote tumor growth and survival by inhibiting proinflammatory signaling and extracellular matrix (ECM) remodeling. In this article, we review how TGF-β activated kinase 1 (TAK1) activation lies at the intersection of proinflammatory signaling by immune receptors and anti-inflammatory signaling by TGF-β receptors. Additionally, we discuss the role of TGF-β in the mechanobiology of cancer. Understanding how TGF-β dampens proinflammatory responses and induces pro-survival mechanical signals throughout cancer development is critical for designing therapeutics that …

Borrelia Burgdorferi Spovg Dna- And Rna-Binding Protein Modulates The Physiology Of The Lyme Disease Spirochete, Christina R. Savage, Brandon L. Jutras, Aaron Bestor, Kit Tilly, Patricia A. Rosa, Yvonne Tourand, Philip E. Stewart, Catherine A. Brissette, Brian Stevenson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The SpoVG protein of Borrelia burgdorferi, the Lyme disease spirochete, binds to specific sites of DNA and RNA. The bacterium regulates transcription of spoVG during the natural tick-mammal infectious cycle and in response to some changes in culture conditions. Bacterial levels of spoVG mRNA and SpoVG protein did not necessarily correlate, suggesting that posttranscriptional mechanisms also control protein levels. Consistent with this, SpoVG binds to its own mRNA, adjacent to the ribosome-binding site. SpoVG also binds to two DNA sites in the glpFKD operon and to two RNA sites in glpFKD mRNA; that operon encodes genes necessary for glycerol catabolism …

Samhd1 Phosphorylation Coordinates The Anti-Hiv-1 Response By Diverse Interferons And Tyrosine Kinase Inhibition., Matthew A Szaniawski, Adam M Spivak, James E Cox, Jonathan L Catrow, Timothy Hanley, Elizabeth S C P Williams, Michel J Tremblay, Alberto Bosque, Vicente Planelles

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Macrophages are susceptible to human immunodeficiency virus type 1 (HIV-1) infection despite abundant expression of antiviral proteins. Perhaps the most important antiviral protein is the restriction factor sterile alpha motif domain and histidine/aspartic acid domain-containing protein 1 (SAMHD1). We investigated the role of SAMHD1 and its phospho-dependent regulation in the context of HIV-1 infection in primary human monocyte-derived macrophages and the ability of various interferons (IFNs) and pharmacologic agents to modulate SAMHD1. Here we show that stimulation by type I, type II, and to a lesser degree, type III interferons share activation of SAMHD1 via dephosphorylation at threonine-592 as a …

Allatostatin C Modulates Nociception And Immunity In Drosophila., Nathaniel D Bachtel, Gary A Hovsepian, Douglas F Nixon, Ioannis Eleftherianos

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Bacterial induced inflammatory responses cause pain through direct activation of nociceptive neurons, and the ablation of these neurons leads to increased immune infiltration. In this study, we investigated nociceptive-immune interactions in Drosophila and the role these interactions play during pathogenic bacterial infection. After bacterial infection, we found robust upregulation of ligand-gated ion channels and allatostatin receptors involved in nociception, which potentially leads to hyperalgesia. We further found that Allatostatin-C Receptor 2 (AstC-R2) plays a crucial role in host survival during infection with the pathogenic bacterium Photorhabdus luminescens. Upon examination of immune signaling in AstC-R2 deficient mutants, we demonstrated that Allatostatin-C …

The State Of The Translational Chaperone Icd-1 During Apoptosis In Caenorhabditis Elegans, Kyle Cicalese

Senior Honors Projects, 2010-2019

The unfolded protein response (UPR) is a signal transduction cascade that mitigates low levels of misfolded protein stress in the endoplasmic reticulum (ER) in an effort to save the affected cell, while prolonged and/or acute ER stress leads to UPR-initiated apoptosis (programmed cell death). One putative step driving apoptosis is the cleavage of chaperones, proteins tasked to help misfolded proteins refold, by caspases, proteases essential to the execution of apoptosis. We are studying the nascent polypeptide-associated complex (NAC), a heterodimeric chaperone complex essential for viability, to determine if its beta subunit is cleaved by caspases during apoptosis to prevent the …