Medical Genetics Commons^™

Bhlhe40 Regulates The T-Cell Effector Function Required For Tumor Microenvironment Remodeling And Immune Checkpoint Therapy Efficacy, Avery J Salmon, Alexander S Shavkunov, Qi Miao, Nicholas N Jarjour, Sunita Keshari, Ekaterina Esaulova, Charmelle D Williams, Jeffrey P Ward, Anna M Highsmith, Josué E Pineda, Reshma Taneja, Ken Chen, Brian T Edelson, Matthew M Gubin

Faculty, Staff and Student Publications

Immune checkpoint therapy (ICT) using antibody blockade of programmed cell death protein 1 (PD-1) or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) can provoke T cell-dependent antitumor activity that generates durable clinical responses in some patients. The epigenetic and transcriptional features that T cells require for efficacious ICT remain to be fully elucidated. Herein, we report that anti-PD-1 and anti-CTLA-4 ICT induce upregulation of the transcription factor BHLHE40 in tumor antigen-specific CD8+ and CD4+ T cells and that T cells require BHLHE40 for effective ICT in mice bearing immune-edited tumors. Single-cell RNA sequencing of intratumoral immune cells in BHLHE40-deficient mice revealed differential …

The Role Of Obesity In Macrophage-Mediated Mechanisms Promoting Early-Onset Colon Cancer., Katharina Marietta Scheurlen

Electronic Theses and Dissertations

Early-onset colon cancer (EOCC) is a leading cause of cancer death among people younger than 50 years of age in the United States and is associated with metabolic dysfunction and obesity. Anti-inflammatory tumor-associated macrophages (TAM) and low Peroxisome Proliferator Activated Receptor Gamma (PPARγ) gene expression in colon cancer (CC) tissue promote tumor progression and decreased patient survival. Obesity-related hormones, such as leptin and adiponectin, have the potential to affect gene expression in TAM to promote CC progression and thereby link obesity and EOCC. The aim of this project was to identify target genes in human CC and to investigate the …

Exploiting 4–1bb Immune Checkpoint To Enhance The Efficacy Of Oncolytic Virotherapy For Diffuse Intrinsic Pontine Gliomas, Virginia Laspidea, Montserrat Puigdelloses, Sara Labiano, Lucía Marrodán, Marc Garcia-Moure, Marta Zalacain, Marisol Gonzalez-Huarriz, Naiara Martínez-Vélez, Iker Ausejo-Mauleon, Daniel De La Nava, Guillermo Herrador-Cañete, Javier Marco-Sanz, Elisabeth Guruceaga, Carlos E De Andrea, María Villalba, Oren Becher, Massimo Squatrito, Verónica Matía, Jaime Gállego Pérez-Larraya, Ana Patiño-García, Sumit Gupta, Candelaria Gomez-Manzano, Juan Fueyo, Marta M Alonso

Faculty, Staff and Student Publications

Diffuse intrinsic pontine gliomas (DIPGs) are aggressive pediatric brain tumors, and patient survival has not changed despite many therapeutic efforts, emphasizing the urgent need for effective treatments. Here, we evaluated the anti-DIPG effect of the oncolytic adenovirus Delta-24-ACT, which was engineered to express the costimulatory ligand 4-1BBL to potentiate the antitumor immune response of the virus. Delta-24-ACT induced the expression of functional 4-1BBL on the membranes of infected DIPG cells, which enhanced the costimulation of CD8+ T lymphocytes. In vivo, Delta-24-ACT treatment of murine DIPG orthotopic tumors significantly improved the survival of treated mice, leading to long-term survivors that developed …

Peripheral And Central Kynurenine Pathway Abnormalities In Major Depression, Elisabeth R Paul, Lilly Schwieler, Sophie Erhardt, Sandra Boda, Ada Trepci, Robin Kämpe, Anna Asratian, Lovisa Holm, Adam Yngve, Robert Dantzer, Markus Heilig, J Paul Hamilton, Martin Samuelsson

Faculty, Staff and Student Publications

Considerable data relate major depressive disorder (MDD) with aberrant immune system functioning. Pro-inflammatory cytokines facilitate metabolism of tryptophan along the kynurenine pathway (KP) putatively resulting in reduced neuroprotective and increased neurotoxic KP metabolites in MDD, in addition to modulating metabolic and immune function. This central nervous system hypothesis has, however, only been tested in the periphery. Here, we measured KP-metabolite levels in both plasma and cerebrospinal fluid (CSF) of depressed patients (n = 63/36 respectively) and healthy controls (n = 48/33). Further, we assessed the relation between KP abnormalities and brain-structure volumes, as well as body mass index (BMI), an …

Serglycin Is Involved In Tgf-Β Induced Epithelial-Mesenchymal Transition And Is Highly Expressed By Immune Cells In Breast Cancer Tissue, Marta Tellez-Gabriel, Xavier Tekpli, Trine M Reine, Beate Hegge, Stephanie R Nielsen, Meng Chen, Line Moi, Lisa Svartdal Normann, Lill-Tove R Busund, George A Calin, Gunhild M Mælandsmo, Maria Perander, Achilleas D Theocharis, Svein O Kolset, Erik Knutsen

Faculty, Staff and Student Publications

Serglycin is a proteoglycan highly expressed by immune cells, in which its functions are linked to storage, secretion, transport, and protection of chemokines, proteases, histamine, growth factors, and other bioactive molecules. In recent years, it has been demonstrated that serglycin is also expressed by several other cell types, such as endothelial cells, muscle cells, and multiple types of cancer cells. Here, we show that serglycin expression is upregulated in transforming growth factor beta (TGF-β) induced epithelial-mesenchymal transition (EMT). Functional studies provide evidence that serglycin plays an important role in the regulation of the transition between the epithelial and mesenchymal phenotypes, …

Defective Dna Polymerase Beta Invoke A Cytosolic Dna Mediated Inflammatory Response, Shengyuan Zhao, Julia A Goewey Ruiz, Manu Sebastian, Dawit Kidane

Faculty, Staff and Student Publications

Base excision repair (BER) has evolved to maintain the genomic integrity of DNA following endogenous and exogenous agent induced DNA base damage. In contrast, aberrant BER induces genomic instability, promotes malignant transformation and can even trigger cancer development. Previously, we have shown that deoxyribo-5'-phosphate (dRP) lyase deficient DNA polymerase beta (POLB) causes replication associated genomic instability and sensitivity to both endogenous and exogenous DNA damaging agents. Specifically, it has been established that this loss of dRP lyase function promotes inflammation associated gastric cancer. However, the way that aberrant POLB impacts the immune signaling and inflammatory responses is still unknown. Here …

Identification Of Lung Cancer Drivers By Comparison Of The Observed And The Expected Numbers Of Missense And Nonsense Mutations In Individual Human Genes, Olga Y Gorlova, Marek Kimmel, Spiridon Tsavachidis, Christopher I Amos, Ivan P Gorlov

Faculty, Staff and Students Publications

Largely, cancer development is driven by acquisition and positive selection of somatic mutations that increase proliferation and survival of tumor cells. As a result, genes related to cancer development tend to have an excess of somatic mutations in them. An excess of missense and/or nonsense mutations in a gene is an indicator of its cancer relevance. To identify genes with an excess of potentially functional missense or nonsense mutations one needs to compare the observed and expected numbers of mutations in the gene. We estimated the expected numbers of missense and nonsense mutations in individual human genes using (i) the …

Environmental And Genetic Factors Affecting Bone Diseases And Phenotypes In Mouse Models, Wei Dong

Theses and Dissertations (ETD)

Bone diseases and phenotypes are affected in multiple ways. We focused on studying the effects of genetic and environmental factors, especially their impact on bone properties. Firstly, we investigated the effects of β-caryophyllene (BCP), a naturally occurring dietary cannabinoid, on protecting bone from vitamin D deficiency in mice fed on a diet lacking or supplemented with vitamin D (VD). We found that the VD-deficient diet enhanced the length of femur and tibia bones (P<0.05), and increased bone volume (BV; P<0.01) and the trabecular bone volume fraction (BV/TV; P <0.01) compared to the D+ diet. When given BCP-containing diet, mice exhibited higher BV and bone mineral density (BMD; P<0.05) than the control group. The trabecular and cortical bone were also affected by VD and BCP. In addition, the inclusion of dietary BCP improved the serum concentrations of klotho (P < 0.05). In summary, these data indicate that BCP enhances the level of klotho in the serum, leading to improved bone properties and mineralization in an experimental mouse model. Under conditions lacking UV light, the D-deficient diet could affect multiple properties of bone, including trabecular and cortical bone, in mice. The D-deficient diet can also result in weight loss in mice.

My second project is to evaluate the bone properties in a mouse model with Il-1rn mutation. When knockout for IL-1rn, mice of Balb/c genomic background exhibited …

Investigating The Role Of Znf384 Rearrangements In Acute Leukemia, Kirsten Dickerson

Theses and Dissertations (ETD)

Chromosomal rearrangements involving ZNF384 are the defining lesion in 5% of pediatric and adult B-cell acute lymphoblastic leukemia and tumors are characterized by aberrant myeloid marker expression. Additionally, ZNF384 rearrangements are the defining lesion in nearly half of pediatric B/myeloid mixed phenotype acute leukemia. These fusions juxtapose full-length ZNF384 to the N terminal portion of a diverse range of partners, most often, transcription factors or epigenetic modifiers. It has been shown that ZNF384-rearranged tumors have a distinct gene expression profile that is consistent between disease groups and N terminal partners. Genomic analyses of patient tumors has shown that ZNF384 fusions …

Dissecting Drivers Of Basal Immunity And Acute Responses To Viral Infection, Aisha Nadia Hegab Souquette

Theses and Dissertations (ETD)

Heterogeneity in the human immune system can lead to limited vaccine efficacy, poor response to therapeutics, increased susceptibility to immune mediated diseases, and differential outcome to infection. Studies to date have suggested a role for biological, environmental, and genetic factors in immune variation; however, they are often focused on a specific subset of the population (e.g. ancestral group, age range) which can exclude phenotypes unique to a diverse population and bias results. To address this gap, we have utilized samples from healthy or influenza virus infected subjects from 8 distinct populations in 5 countries to conduct an integrative analysis of …

Tumor Somatic Mutations Also Existing As Germline Polymorphisms May Help To Identify Functional Snps From Genome-Wide Association Studies, Ivan P Gorlov, Xiangjun Xia, Spiridon Tsavachidis, Olga Y Gorlova, Christopher I Amos

Faculty, Staff and Students Publications

We hypothesized that a joint analysis of cancer risk-associated single-nucleotide polymorphism (SNP) and somatic mutations in tumor samples can predict functional and potentially causal SNPs from GWASs. We used mutations reported in the Catalog of Somatic Mutations in Cancer (COSMIC). Confirmed somatic mutations were subdivided into two groups: (1) mutations reported as SNPs, which we call mutational/SNPs and (2) somatic mutations that are not reported as SNPs, which we call mutational/noSNPs. It is generally accepted that the number of times a somatic mutation is reported in COSMIC correlates with its selective advantage to tumors, with more frequently reported mutations being …

Immunohistochemical Pattern– A Prognostic Factor For Synchronous Gastrointestinal Cancer, Catalin Alius, Catalin Gabriel Cirstoveanu, Cristinel Dumitru Badiu, Valeriu Ardeleanu, Vasile Adrian Dumitru

Journal of Mind and Medical Sciences

Recent advancements in medical genetics and molecular biology are reflected in the modern understanding and approach to colorectal carcinoma (CRC). Understanding the cellular mechanisms and mutational patterns that promote carcinogenesis could enhance the predictive accuracy of the TNM classification. Furthermore, this will allow for a much more documented stratification and tailored oncological treatment. This paper presents an illustrative case of a relatively young patient (50 years old) with no family history of cancer who was diagnosed with four synchronous gastrointestinal (GI) adenocarcinomas displaying a wild type P53, negative BRAF testing, and mutated MLH1 and PMS2 proteins. This case report contributes …

A Novel Methodology To Identify The Primary Topics Contained Within The Covid-19 Research Corpus, Allen Crane, Brock Freidrich, William Fehlman, Igor Frolow, Daniel W. Engels

SMU Data Science Review

In this paper, we present a novel framework and system for the identification of primary research topics from within a corpus of related publications, the classification of individual publications according to these topics, and the results of the application of our framework and system to the COVID-19 Open Research Dataset (CORD-19). CORD-19 is a corpus of published peer reviewed and pre-peer reviewed articles related to the coronavirus that causes COVID-19. Using machine learning techniques, such as Non-negative Matrix Factorization for Natural Language Processing and a Bayesian classifier, we developed a novel framework and system that automatically extracts sparse and meaningful …

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 …

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 …

Tumor Immunotherapy: Mechanisms Of Acquired Resistance And Characterization Of Immune Related To Xicities, Ashvin Jaiswal

Dissertations and Theses (Open Access)

Tumor immunotherapy has shown very promising clinical benefit across an array of cancers; however, two major challenges remain unresolved in the field. First, many patients do not respond to therapy at all or relapse after a period of remission. Second, there are often dose-limiting immune related adverse effects associated with immunomodulation.

In order to understand the mechanisms employed by tumors to evade immunotherapeutic responses, we established a murine model of melanoma designed to elucidate the molecular mechanisms underlying immunotherapy resistance. Through multiple in vivo passages, we selected a B16 melanoma tumor line that evolved complete resistance to combination blockade of …

Small Rna Teg49 Is Derived From A Sara Transcript And Regulates Virulence Genes Independent Of Sara In Staphylococcus Aureus, Adhar Manna, Samin Kim, Liviu Cengher, Anna Corvaglia, Stefano Leo, Patrice Francois, Ambrose L. Cheung

Dartmouth Scholarship

Expression of virulence factors in Staphylococcus aureus is regulated by a wide range of transcriptional regulators, including proteins and small RNAs (sRNAs), at the level of transcription and/or translation. The sarA locus consists of three overlapping transcripts generated from three distinct promoters, all containing the sarA open reading frame (ORF). The 5= untranslated regions (UTRs) of these transcripts contain three separate regions 711, 409, and 146 nucleotides (nt) upstream of the sarA translation start, the functions of which remain unknown. Re- cent transcriptome-sequencing (RNA-Seq) analysis and subsequent characterization indicated that two sRNAs, teg49 and teg48, are processed and likely produced …

Requirements For Pseudomonas Aeruginosa Type I-F Crispr-Cas Adaptation Determined Using A Biofilm Enrichment Assay, Gary E. Heussler, Jon L. Miller, Courtney E. Price, Alan J. Collins

Dartmouth Scholarship

CRISPR (clustered regularly interspaced short palindromic repeat)-Cas (CRISPR-associated protein) systems are diverse and found in many archaea and bacteria. These systems have mainly been characterized as adaptive immune systems able to protect against invading mobile genetic elements, including viruses. The first step in this protection is acquisition of spacer sequences from the invader DNA and incorporation of those sequences into the CRISPR array, termed CRISPR adaptation. Progress in understanding the mechanisms and requirements of CRISPR adaptation has largely been accomplished using overexpression of cas genes or plasmid loss assays; little work has focused on endogenous CRISPR-acquired immunity from viral predation. …

Diagnostics Of Primary Immunodeficiencies Through Next-Generation Sequencing., Vera Gallo, Laura Dotta, Giuliana Giardino, Emilia Cirillo, Vassilios Lougaris, Roberta D'Assante, Alberto Prandini, Rita Consolini, Emily G. Farrow, Isabelle Thiffault, Carol J. Saunders, Antonio Leonardi, Alessandro Plebani, Raffaele Badolato, Claudio Pignata

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Recently, a growing number of novel genetic defects underlying primary immunodeficiencies (PIDs) have been identified, increasing the number of PID up to more than 250 well-defined forms. Next-generation sequencing (NGS) technologies and proper filtering strategies greatly contributed to this rapid evolution, providing the possibility to rapidly and simultaneously analyze large numbers of genes or the whole exome.

OBJECTIVE: To evaluate the role of targeted NGS and whole exome sequencing (WES) in the diagnosis of a case series, characterized by complex or atypical clinical features suggesting a PID, difficult to diagnose using the current diagnostic procedures.

METHODS: We retrospectively analyzed …

Ceramides Promote Apoptosis For Virus-Infected Lymphoma Cells Through Induction Of Ceramide Synthases And Viral Lytic Gene Expression, Lu Dai, Jimena Trillo-Tinoco, Aiping Bai, Yihan Chen, Jacek Bielawski, Luis Del Valle, Charles D. Smith, Augusto C. Ochoa, Zhiqiang Qin, Chris Parsons

School of Medicine Faculty Publications

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent for several human cancers including primary effusion lymphoma (PEL), a rapidly progressive malignancy arising preferentially in immunocompromised patients. With conventional chemotherapy, PEL continues to portend high mortality, dictating the development of novel therapeutic strategies. Sphingosine kinase 2 (SphK2) represents a key gatekeeper for sphingolipid metabolism, responsible for conversion of ceramides to sphingosine-1-phosphate (S1P). We have previously demonstrated that targeting SphK2 using a novel selective inhibitor, ABC294640, leads to intracellular accumulation of ceramides and induces apoptosis for KSHV-infected PEL cells, while suppressing tumor progression in vivo. In the current study, we sought to …

Autoimmune Susceptibility Imposed By Public Tcrβ Chains, Yunqian Zhao

Theses and Dissertations (ETD)

The major histocompatibility complex (MHC) is the strongest genetic risk factor for autoimmunity. It acts together with a corresponding TCR repertoire, yet, considering the extent of the repertoire's diversity, how this imposes disease susceptibility on a population is not well understood. We address the hypothesis that shared or public TCR, those present in most individuals, modulate autoimmune risk. High resolution analyses of autoimmune encephalomyelitis-associated T-cell receptor β chain (TCRβ) showed preferential utilization of public TCR sequences, implicating them in pathogenesis. Disease-associated public TCRβ, when transgenically expressed in association with endogenously rearranged T-cell receptor α chain (TCRα), could further endow unprimed …

Co-Infection With Hpv Types From The Same Species Provides Natural Cross-Protection From Progression To Cervical Cancer, Rafal S. Sobota, Doreen Ramogola-Masire, Scott M. Williams, Nicola M. Zetola

Dartmouth Scholarship

The worldwide administration of bivalent and quadrivalent HPV vaccines has resulted in cross-protection against non-vaccine HPV types. Infection with multiple HPV types may offer similar cross-protection in the natural setting. We hypothesized that infections with two or more HPV types from the same species, and independently, infections with two or more HPV types from different species, associate with protection from high-grade lesions.

Regulation Of Hepatic Gene Expression During Liver Development And Disease, Hui Ren

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

My first project was to investigate the role of Hepatocyte Nuclear Factor 1 (HNF1) and Nuclear Factor I (NFI) on alpha-fetoprotein (AFP) promoter activity during liver development. AFP is highly expressed in the fetal liver, silenced at birth, and remains at very low levels in the adult liver. A GA substitution located at -119 of the human AFP promoter is associated with hereditary persistence of AFP (HPAFP) expression in the adult liver (Hum Molec Genet, 1993, 2:379). The -120 region harbors overlapping binding sites for HNF1 and NFI. While it has been shown that the GA substitution increases HNF1 binding, …

Signaling Mechanisms Involved In The Generation Of Human Peripheral Itregs, Mary Catherine Reneer

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Maintaining balance in the human immune system is critical for the body’s ability to discriminate between foreign and self-antigens. This balance is achieved, in part, by a subpopulation of T cells known as induced regulatory T cells (iTregs). Dysregulation of this population may contribute to the onset and progression of cancer, chronic inflammation and autoimmune diseases. Therefore, manipulation of iTreg development holds promising therapeutic potential; however, studying this vital population has proven difficult due to low numbers, heterogeneous cell populations, substantial phenotypic differences between mouse and human cells, and the high plasticity seen in iTregs. These current limitations have prevented …

Effects Of Apoptotic Cell Accumulation Caused By Mer Deficiency On Germinal Center B Cells And Helper T Cells, Tahsin N. Khan, Eric B. Wong, Ziaur S.M. Rahman

Department of Microbiology and Immunology Faculty Papers

Mer (MerTK), a member of the Tyro-3/Axl/Mer subfamily receptor tyrosine kinases, expression on phagocytes facilitates their clearance of apoptotic cells (ACs). Mer expression in germinal centers (GCs) occurs predominantly on tingible body macrophages. B and T cells do not express Mer. Mer deficiency (Mer-/-) results in the accumulation of ACs in GCs and augmented antibody-forming cell (AFC), GC and IgG2 Ab responses against T-dependent (TD) Ag. Here, we show that AC accumulation in GCs and elevated AFC, GC and IgG2 Ab responses in Mer-/- mice lasted for at least 80 days after immunization with NP-OVA. Enhanced responses and AC accumulation …

Hiv Rna Suppression And Immune Restoration: Can We Do Better?, Marilia Rita Pinzone, Michelino Di Rosa, Bruno Cacopardo, Giuseppe Nunnari

Department of Microbiology and Immunology Faculty Papers

HAART has significantly changed the natural history of HIV infection: patients receiving antiretrovirals are usually able to control viremia, even though not all virological responders adequately recover their CD4+ count. The reasons for poor immune restoration are only partially known and they include genetic, demographic and immunologic factors. A crucial element affecting immune recovery is immune activation, related to residual viremia; indeed, a suboptimal virological control (i.e., low levels of plasma HIV RNA) has been related with higher levels of chronic inflammation and all-cause mortality. The sources of residual viremia are not yet completely known, even though the most important …

Cns Recruitment Of Cd8+ T Lymphocytes Specific For A Peripheral Virus Infection Triggers Neuropathogenesis During Polymicrobial Challenge., Christine M Matullo, Kevin J O'Regan, Mark Curtis, Glenn F Rall

Department of Microbiology and Immunology Faculty Papers

Although viruses have been implicated in central nervous system (CNS) diseases of unknown etiology, including multiple sclerosis and amyotrophic lateral sclerosis, the reproducible identification of viral triggers in such diseases has been largely unsuccessful. Here, we explore the hypothesis that viruses need not replicate in the tissue in which they cause disease; specifically, that a peripheral infection might trigger CNS pathology. To test this idea, we utilized a transgenic mouse model in which we found that immune cells responding to a peripheral infection are recruited to the CNS, where they trigger neurological damage. In this model, mice are infected with …

Buffered Memory: A Hypothesis For The Maintenance Of Functional, Virus-Specific Cd8(+) T Cells During Cytomegalovirus Infection., Christopher M Snyder

Department of Microbiology and Immunology Faculty Papers

Chronic infections have been a major topic of investigation in recent years, but the mechanisms that dictate whether or not a pathogen is successfully controlled are incompletely understood. Cytomegalovirus (CMV) is a herpesvirus that establishes a persistent infection in the majority of people in the world. Like other herpesviruses, CMV is well controlled by an effective immune response and induces little, if any, pathology in healthy individuals. However, controlling CMV requires continuous immune surveillance, and thus, CMV is a significant cause of morbidity and death in immune-compromised individuals. T cells in particular play an important role in controlling CMV and …

Epitope Characterization Of Sero-Specific Monoclonal Antibody To Clostridium Botulinum Neurotoxin Type A., Cindi R Corbett, Erin Ballegeer, Kelly A Weedmark, M D Elias, Fetweh H Al-Saleem, Denise M Ancharski, Lance L Simpson, Jody D Berry

Department of Medicine Faculty Papers

Botulinum neurotoxins (BoNTs) are extremely potent toxins that can contaminate foods and are a public health concern. Anti-BoNT antibodies have been described that are capable of detecting BoNTs; however there still exists a need for accurate and sensitive detection capabilities for BoNTs. Herein, we describe the characterization of a panel of eight monoclonal antibodies (MAbs) generated to the non-toxic receptor-binding domain of BoNT/A (H(C)50/A) developed using a high-throughput screening approach. In two independent hybridoma fusions, two groups of four IgG MAbs were developed against recombinant H(C)50/A. Of these eight, only a single MAb, F90G5-3, bound to the whole BoNT/A protein …

The Characteristics Of Borrelia Hermsii Infection In Human Hematopoeitic Stem Cell-Engrafted Mice Mirror Those Of Human Relapsing Fever, Raja Vuyyuru, Hongqi Liu, Tim Manser, Kishore Alugupalli

Department of Microbiology and Immunology Faculty Papers

Rodents are natural reservoirs for a variety of species of Borrelia that cause relapsing fevers in humans. The murine model of this disease recapitulates many of the clinical manifestations of the human disease and has revealed that T cell-independent antibody responses are required to resolve the bacteremic episodes. However, it is not clear whether such protective humoral responses are mounted in humans.