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Theses/Dissertations

Immunology and Infectious Disease

2013

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Tissue-Dependent T Cell Apoptosis And Transcriptional Regulation Of Memory Cd8+T Cell Differentiation During Viral Infections: A Dissertation, Varun N. Kapoor Dec 2013

Tissue-Dependent T Cell Apoptosis And Transcriptional Regulation Of Memory Cd8+T Cell Differentiation During Viral Infections: A Dissertation, Varun N. Kapoor

GSBS Dissertations and Theses

Activation and proliferation of antigen-specific T cells is the hallmark of an anti-viral immune response. Effector T cells generated during an immune response are heterogeneous in regards to their ability to populate the memory pool once the immune response has resolved. Initial T cell activation takes place in the lymphoid organs, after which T cells migrate into the non-lymphoid tissues. The presence of memory T cells at non-lymphoid tissue sites has been shown to be critical for protection against secondary virus challenge. Our lab has previously demonstrated that during and after the resolution of the immune response to Lymphocytic choriomeningitis ...


Development Of Novel Antifungal Peptides Based On A Natural Model Of Histatin-5 Peptide, Duy Tu Nguyen Dec 2013

Development Of Novel Antifungal Peptides Based On A Natural Model Of Histatin-5 Peptide, Duy Tu Nguyen

Theses and Dissertations

Our research group is working toward the development of novel antifungal peptides based on a natural model of peptide histatin-5. Histatin-5 is found in human saliva and known to protect our body against oral infections by Candida species. Candidiasis, or an infection caused by Candida species, is considered one of the most medically important fungal infections worldwide. Blood stream infections caused by Candida species are the fourth leading cause of hospital-acquired fungal infections that is associated with high mortality rates and high costs of treatment. This study investigated the modes of action of histatin-5 with the use of one 16-mer ...


Characterizing The Effect Of Dasatinib On Anti-Tumor Immune Response And Exploring The Potential Of Combining Targeted Therapy And Immunotherapy In A C-Kit Mutant Mastocytoma Model, Yan Yang Dec 2013

Characterizing The Effect Of Dasatinib On Anti-Tumor Immune Response And Exploring The Potential Of Combining Targeted Therapy And Immunotherapy In A C-Kit Mutant Mastocytoma Model, Yan Yang

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Targeted therapy and immunotherapy eradicate malignant cells through different mechanisms, and the strengths and weaknesses of these two approaches are potentially complementary. Therefore, the combination of molecular targeted drugs with immune- based therapies is considered an attractive approach for improving the therapeutic efficacy of cancer treatment. The mutation and amplification of the c-KIT proto- oncogene are associated with multiple different cancer types, and multiple c-KIT inhibitors have been tested clinically. In spite of some encouraging results using these agents, most patients with c-KIT mutant cancers still relapse due to drug resistance. This also demonstrates the inherent limitation of molecular targeted ...


C-Jun N-Terminal Kinases Regulate Adenovirus-Mediated Autophagy And Antigen Presentation, Sarah R. Klein Dec 2013

C-Jun N-Terminal Kinases Regulate Adenovirus-Mediated Autophagy And Antigen Presentation, Sarah R. Klein

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Targeted immunotherapy with recombinant, oncolytic adenoviruses is under investigation for the treatment of cancer. Evidence indicates adenoviruses induce autophagy that is required for oncolysis, but the molecular regulation of autophagy in infected cells remains under investigation. Our data suggested the canonical pathway regulating starvation-induced autophagy was not implemented in adenovirus-induced autophagy; however, adenovirus infection triggered phosphorylation of c-Jun N-terminal kinases (JNK) that was essential for autophagy. Adenoviral replication within the host cell elicited JNK pathway activation leading to B cell lymphoma-2 (Bcl-2) phosphorylation. JNK-dependent Bcl-2 phosphorylation stimulated the dissociation of Bcl-2/beclin 1 heterodimers, enabling beclin 1 to initiate autophagy ...


Plasmodium Suppresses T Cell Responses To Heterologous Infections By Impairing T Cell Activation, Chelsi Elizabeth White Dec 2013

Plasmodium Suppresses T Cell Responses To Heterologous Infections By Impairing T Cell Activation, Chelsi Elizabeth White

Masters Theses

Malaria is a devastating disease caused by parasites of the genus Plasmodium. Plasmodium falciparum, which is responsible for most malaria related fatalities, suppresses host immune responses during heterologous coinfections or following vaccination. However the mechanisms responsible for this defect are not well defined. The mechanism and to what extent this immunosuppression is occurring was investigated. This study demonstrates that both dendritic cell and T cell activation are impaired following a Plasmodium infection, ultimately altering the adaptive T cell response to secondary infections. T cell suppression is evident early on following a secondary infection and continues throughout the peak of parasitemia ...


Mechanisms Of The Anti-Pneumococcal Function Of C-Reactive Protein, Toh B. Gang Dec 2013

Mechanisms Of The Anti-Pneumococcal Function Of C-Reactive Protein, Toh B. Gang

Electronic Theses and Dissertations

Human C-reactive protein (CRP) increases survival of and decreases bacteremia in mice infected with Streptococcus pneumoniae. Such protection of mice against pneumococcal infection is seen only when CRP is administered into mice 6 hours before to 2 hours after the injection of pneumococci, but not when CRP is given to mice at a later time. Our first aim was to define the mechanism of CRP-mediated initial protection of mice against infection. It was proposed that CRP binds to phosphocholine (PCh) moieties present in the cell wall and activates the complement system on the pneumococcal surface that kills the pathogen. We ...


Generation And Characteriztion Of Regulatory Dendritic Cells For The Amelioration Of Acute Graft Versus Host Disease, Sabrina Marie Scroggins Dec 2013

Generation And Characteriztion Of Regulatory Dendritic Cells For The Amelioration Of Acute Graft Versus Host Disease, Sabrina Marie Scroggins

Theses and Dissertations

Despite Human Leukocyte Antigen (HLA) matching and use of immunosuppressive drugs, graft-versus-host disease (GVHD) following hematopoietic stem cell transplant (HSCT) is prevalent and often fatal. Additionally, older HSCT recipients experience increased morbidity and mortality. Prophylactic treatment with age-matched syngeneic (recipient strain-derived) cultured regulatory DC (DCreg) has been shown to decrease GVHD-associated mortality in young bone marrow transplanted (BMT) mice. The purpose of this study was to investigate: 1) the potential to generate DCreg from older mice and their subsequent ability to ameliorate GVHD in older BMT mice, 2) the mechanism(s) by which DCreg mitigate GVHD in vivo, 3) the ...


Retroviral Mutagenesis In A Newly Developed Myc Transgenic Mouse Model Of Human B Cell And Plasma Cell Neoplasia, Samuel Robert Lifton Dec 2013

Retroviral Mutagenesis In A Newly Developed Myc Transgenic Mouse Model Of Human B Cell And Plasma Cell Neoplasia, Samuel Robert Lifton

Theses and Dissertations

Three potential driver genes were identified by use of retroviral mutagenesis in the newly developed iMyc model of B cell malignancy. To do so, iMyc mice, which bear an inserted copy of c-Myc in the IgH locus, were treated with MOL4070LTR to favor the development of B cell malignancies. After tumor development, B cell origin tumors were identified by use of immunohistochemistry and selected for downstream analysis. Three genes were chosen as potential driver genes and validated in mouse or human disease as involved in disease or directly in malignancy. These genes are CD82, IRAK2 and DNMT3a.


The Related Kinases Fak And Pyk2 Serve Distinct Functions In Tcr-Mediated T Cell Activation, Nicole Chapman Dec 2013

The Related Kinases Fak And Pyk2 Serve Distinct Functions In Tcr-Mediated T Cell Activation, Nicole Chapman

Theses and Dissertations

T cells are central regulators of adaptive immunity in infectious and pathophysiological diseases. The activation of T cells is regulated by the T cell antigen receptor (TCR) and co-stimulatory receptors like toll-like receptor 2 (TLR2). These receptors activate distinct and overlapping intracellular signaling pathways that ultimately shape T cell responses. Therefore, studies that elucidate the molecular mechanisms of signal transduction downstream of receptors like the TCR and TLR2 will highlight key pathways required for T cell activation. These pathways could then be clinically targeted to alter dysfunctional T cell responses that promote many human diseases.

Focal adhesion kinase (FAK) and ...


Disparate Activation Of The Inflammasome By Chitin And Chitosan: A Dissertation, Chelsea L. Bueter Sep 2013

Disparate Activation Of The Inflammasome By Chitin And Chitosan: A Dissertation, Chelsea L. Bueter

GSBS Dissertations and Theses

Chitin is an abundant polysaccharide found in fungal cell walls, crustacean shells, and insect exoskeletons. The immunological properties of both chitin and its deacetylated derivative chitosan are of relevance due to frequent natural exposure and their increasing use in translational applications. Depending on the preparation studied and the endpoint measured, these compounds have been reported to induce allergic responses, inflammatory responses, or no response at all. Highly purified chitosan and chitin were prepared and the capacity of these glycans to stimulate the release of the inflammasomeassociated cytokine IL-1β was examined. Chitosan was shown to be a potent inflammasome activator in ...


Characterization Of Staphylococcus Aureus Lipase, Vithooshan Vijayakumaran Aug 2013

Characterization Of Staphylococcus Aureus Lipase, Vithooshan Vijayakumaran

Electronic Thesis and Dissertation Repository

USA300, a strain of community-associated methicillin resistant Staphylococcus aureus (CA-MRSA), has become prevalent in the community. Colonization of human skin requires mechanisms that allow this bacterium to overcome the innate immune defenses on the skin, including secretion of antimicrobial lipids. Antimicrobial lipids inhibit S. aureus growth and induce the staphylococcal proteolytic cascade, producing aureolysin (Aur) which processes the lipase glycerol ester hydrolase (Geh). Nearly all S. aureus strains secrete Geh, yet little information exists concerning its function. Using purified Aur and Geh we confirm that aureolysin processes proGeh to Geh. We then confirmed that geh was required for lipase activity ...


Human Cytomegalovirus Reprograms The Expression Of Host Micro-Rnas Whose Target Networks Are Required For Viral Replication: A Dissertation, Alexander N. Lagadinos Aug 2013

Human Cytomegalovirus Reprograms The Expression Of Host Micro-Rnas Whose Target Networks Are Required For Viral Replication: A Dissertation, Alexander N. Lagadinos

GSBS Dissertations and Theses

The parasitic nature of viruses requires that they adapt to their host environment in order to persist. Herpesviruses are among the largest and most genetically complex human viruses and they have evolved mechanisms that manipulate a variety of cellular pathways and processes required to replicate and persist within their hosts. Human cytomegalovirus (HCMV), a member of the β- herpesvirus sub-family, has the capacity to influence the expression of many host genes in an effort to create an optimal environment for infection. One mechanism utilized by HCMV to alter gene expression is the host RNA interference (RNAi) pathway. This is evidenced ...


Role Of Branched-Chain Amino Acid Transporters In Staphylococcus Aureus Virulence, Sameha Omer Aug 2013

Role Of Branched-Chain Amino Acid Transporters In Staphylococcus Aureus Virulence, Sameha Omer

Electronic Thesis and Dissertation Repository

Branched-chain amino acids (BCAAs) act as effector molecules that signal a global transcriptional regulator, CodY, to regulate virulence factors in nutrient depleted environments. Staphylococcus aureus contains three putative BCAA transporters (BrnQ1, BrnQ2, BrnQ3) whose role in BCAA uptake is unknown. We hypothesize that BrnQ transporters are involved in BCAA uptake and contribute to virulence in S. aureus by modulating CodY activity. Results from radioactive uptake assays indicate that BrnQ1 is the predominant BrnQ transporter of isoleucine, valine and leucine. Meanwhile, BrnQ2 is more specific for isoleucine. Furthermore, only the lack of BrnQ1 hinders growth of S. aureus in chemically-defined media ...


Gene Repression And Cell Cycle Regulation By Pu.1 In Acute Myeloid Leukemia, Rachel Gh Ziliotto Aug 2013

Gene Repression And Cell Cycle Regulation By Pu.1 In Acute Myeloid Leukemia, Rachel Gh Ziliotto

Electronic Thesis and Dissertation Repository

Acute myeloid leukemia (AML) is associated with mutations or chromosomal translocations in genes encoding transcription factors. PU.1 is a transcription factor that is required for the development of nearly all white blood cell types of the immune system, including B cells, granulocytes, and monocytes. Mutation of the gene encoding PU.1, SPI1 in humans and Sfpi1 in mice, is associated with AML. We hypothesized that reduced expression of PU.1 in Sfpi1BN/BNmyeloid cells will result in the development of AML in transplanted mice due to reduced repression of E2F1, leading to deregulation of the cell cycle ...


Elucidating The Role Of Cathepsin B In The Lifecycle Of Influenza A Virus, Macon D. Coleman Aug 2013

Elucidating The Role Of Cathepsin B In The Lifecycle Of Influenza A Virus, Macon D. Coleman

Electronic Thesis and Dissertation Repository

Influenza virus type A (IVA) is the etiologic agent responsible for the febrile respiratory illness referred to as the flu. Seasonal and occasionally pandemic IVA-associated illness is a significant cause of morbidity and mortality worldwide, and presents a significant burden to the healthcare system. Our previous work showed that the propagation of IVA required the lysosomal protease cathepsin B (CTSB), though the mechanism behind this dependency was not elucidated. This study further examined the role of CTSB by using CTSB-deficient (CTSB-/-) macrophages and the CTSB-specific chemical inhibitor CA-074 Me (CaMe) in human lung epithelial cells. CTSB-/- and CA-074 Me-treated cells ...


Modeling Leafhopper Populations And Their Role In Transmitting Plant Diseases., Ji Ruan Aug 2013

Modeling Leafhopper Populations And Their Role In Transmitting Plant Diseases., Ji Ruan

Electronic Thesis and Dissertation Repository

This M.Sc. thesis focuses on the interactions between crops and leafhoppers.

Firstly, a general delay differential equations system is proposed, based on the infection age structure, to investigate disease dynamics when disease latencies are considered. To further the understanding on the subject, a specific model is then introduced. The basic reproduction numbers $\cR_0$ and $\cR_1$ are identified and their threshold properties are discussed. When $\cR_0 < 1$, the insect-free equilibrium is globally asymptotically stable. When $\cR_0 > 1$ and $\cR_1 < 1$, the disease-free equilibrium exists and is locally asymptotically stable. When $\cR_1>1$, the disease will persist.

Secondly, we derive another general delay differential equations system to examine how different life stages of leafhoppers affect crops. The basic reproduction numbers $\cR_0$ is determined ...


Mechanisms Contributing To The Emergence Of Ranavirus In Ectothermic Vertebrate Communities, Roberto M. Brenes Aug 2013

Mechanisms Contributing To The Emergence Of Ranavirus In Ectothermic Vertebrate Communities, Roberto M. Brenes

Doctoral Dissertations

Ranaviruses have been linked to amphibian die-off events in ectothermic vertebrates worldwide. Differences in susceptibility and capacity of transmission among and within classes are poorly understood. My goal was to determine possible mechanisms influencing susceptibility to ranavirus infection in amphibian species and other aquatic vertebrate taxa, as well as the capacity of transmission between classes and the effects of amphibian community composition on ranavirus transmission. I tested 16 amphibian species from USA, Europe, and the pet trade, expanding an existing database developed by the Center for Wildlife Health to 35 amphibian species from 9 families. I also tested the susceptibility ...


Role Of Msa In Immune Evasion, Persistence, And Protease Regulation In The Human Pathogenic Strains Of Staphylococcus Aureus, Maria Deepa Basco Aug 2013

Role Of Msa In Immune Evasion, Persistence, And Protease Regulation In The Human Pathogenic Strains Of Staphylococcus Aureus, Maria Deepa Basco

Dissertations

Opportunistic pathogens like Staphylococcus aureus on entering the host can stay colonized at the foci of infection or evade the immune system to disseminate to other sites. In this study we investigated the regulatory influence of the modulator of sarA (msa) on immune evasion and host persistence, employing the hospital-acquired strain S. aureus UAMS-1 and community-acquired strain S. aureus USA300 LAC. In the murine sepsis model, mutation of the msa gene in LAC showed no change in dissemination of infection; however, in UAMS-1 a decrease in microbial load was observed in the lungs. Differential regulation by the msa gene was ...


T-Cell Treatments For Solid And Hematological Tumors, Drew C. Deniger Aug 2013

T-Cell Treatments For Solid And Hematological Tumors, Drew C. Deniger

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Cell-based therapies have demonstrated potency and efficacy as cancer treatment modalities. T cells can be dichotomized by their T cell receptor (TCR) complexes where alpha/beta T cells (95% of T cells) and gamma/delta T cells (+T cells proliferated to clinically significant numbers and ROR1+ tumor cells were effectively targeted and killed by both ROR1-specific CAR+ T cell populations, although ROR1RCD137 were superior to ROR1RCD28 in clearance of leukemia xenografts in vivo. The second specific aim focused on generating bi-specific CD19-specific CAR+ gamma/delta T cells with polyclonal TCRgamma/delta repertoire on CD19+ artificial antigen presenting cells (aAPC). Enhanced ...


Microsporidia Spore Adherence And Host Cell Infection In Vitro, Cory A. Leonard Aug 2013

Microsporidia Spore Adherence And Host Cell Infection In Vitro, Cory A. Leonard

Electronic Theses and Dissertations

Microsporidia infect invertebrate and vertebrate animals. Human pathogenic microsporidia are associated with severe disease in immunocompromised individuals, and mostly asymptomatic infection in the immunocompetent. Treatment options for microsporidiosis are limited, incompletely effective, and associated with toxicity. Furthermore, microsporidia infection of healthy individuals is poorly understood, and the consequences of asymptomatic infection have not been determined. Little is known about the molecular mechanisms of microsporidia infection, but such information is essential for the development of new therapies. Spores adhere to host cell surfaces in vitro. Our laboratory has focused on determining specific host cell and microsporidia spore surface participants in spore ...


Trends In Borrelia Spp. Prevalence In Ixodes Spp. Ticks From The Southeastern Coastal United States, Lauren Paul Maestas Aug 2013

Trends In Borrelia Spp. Prevalence In Ixodes Spp. Ticks From The Southeastern Coastal United States, Lauren Paul Maestas

Masters Theses

The Lyme borreliosis (LB) cycle, involving Ixodes scapularis and Borrelia burgdorferi sensu stricto (Bbss), is well documented in the northeastern US, where LB is becoming increasingly prevalent. In coastal North Carolina, I. affinis has been shown to have a higher incidence of Bbss than I. scapularis. My objectives were, to assess changes in prevalence of Bbss in Ixodes spp. along a transect from Virginia to Florida, and to assess the value of dogs and mesomammals as sentinels for spread of Borrelia burgdorferi sensu lato.

Ixodes spp. were collected at sites from 37.4o N to 30.0o N ...


Prevalence And Transmission Potential Of Borrelia Burgdorferi In Three Species Of Wildcaught Plestiodon Spp. Skinks Of The Southeastern United States, Teresa Dianne Moody Aug 2013

Prevalence And Transmission Potential Of Borrelia Burgdorferi In Three Species Of Wildcaught Plestiodon Spp. Skinks Of The Southeastern United States, Teresa Dianne Moody

Masters Theses

In the southeastern United States, blue-tailed skinks (Plestiodon spp.) are important hosts for Ixodes scapularis ticks, the principal vector of Lyme disease (LD) in this region. Skinks and other southeastern lizards are not thought to be reservoir competent for Borrelia burgdorferi sensu stricto (Bbss), the etiological agent of LD in the United States. . Lizard-feeding by southeastern I. scapularis may tend to suppress sylvatic cycles of B. burgdorferi, and thus may be an important reason why LD case rates in the Southeast are much lower than in the Northeast and upper Midwest. Nevertheless, some skinks in Florida and South Carolina have ...


The Role Of Heterologous Immunity In Viral Co-Infections And Neonatal Immunity: A Dissertation, Laurie L. Kenney Aug 2013

The Role Of Heterologous Immunity In Viral Co-Infections And Neonatal Immunity: A Dissertation, Laurie L. Kenney

GSBS Dissertations and Theses

The dynamics of T cell responses have been extensively studied during single virus infection of naïve mice. During a viral infection, viral antigen is presented in the context of MHC class I molecules on the surface of infected cells. Activated CD8 T cells that recognized viral antigens mediate clearance of virus through lysis of these infected cells. We hypothesize that the balance between the replicating speed of the virus and the efficiency at which the T cell response clears the virus is key in determining the disease outcome of the host. Lower T cell efficiency and delayed viral clearance can ...


Itk Is A Dual Action Regulator Of Immunoreceptor Signaling In The Innate And Adaptive Immune System: A Dissertation, John W. Evans Iii Jul 2013

Itk Is A Dual Action Regulator Of Immunoreceptor Signaling In The Innate And Adaptive Immune System: A Dissertation, John W. Evans Iii

GSBS Dissertations and Theses

The cells and molecules that comprise the immune system are essential for mounting an effective response against microbes. A successful immune response limits pathology within the host while simultaneously eliminating the pathogen. The key to this delicate balance is the correct recognition of the pathogen and the appropriate response of immune cells. Cellular activation originates through receptors that relay information about the state of the microenvironment to different compartments within the cell. The rapid relay of information is called signal transduction and employs a network of signaling mediators such as kinases, phosphatases, adaptor molecules, and transcription factors. IL-2 inducible T ...


The Role Of Α5gaba(A) Receptors In Brain Inflammation, Jason K. Wong Jul 2013

The Role Of Α5gaba(A) Receptors In Brain Inflammation, Jason K. Wong

Electronic Thesis and Dissertation Repository

Microglia critically regulate brain inflammation. GABAA receptors that contain the α5-subunit (α5GABAA) exhibit high sensitivity to GABA and confer tonic activity. Moreover, α5GABA­A receptors have been associated with brain inflammation. This study investigates the role of α5GABAA receptors in microglial activation. Immunohistochemistry revealed that in response to intraperitoneal lipopolysaccharide (LPS), α5-subunit null mice exhibited significantly higher expression of IL-1β in hippocampal microglia. Neuronal-glial co-cultures treated with α5GABA­A receptor inverse agonist L655,708 drastically increased microglial IL-1β expression. Surprisingly, ELISA of media from L655,708-treated co-cultures revealed a considerably lower concentration of IL-1β. Treating cultured primary ...


Priming And Tracking The Virus-Specific T Cell Response, Daniel Scott Mcdermott Jul 2013

Priming And Tracking The Virus-Specific T Cell Response, Daniel Scott Mcdermott

Theses and Dissertations

CD4 and CD8 T cells play a vital role in mediating the clearance of viral pathogens following infection. Mice deficient- or depleted of their CD4 and/or CD8 T cells exhibit a diminished ability to control viral replication following infection and in some cases develop a persistent viral infection. CD8 T cells upregulate cytotoxic effector molecules such as granzyme B, Fas and TNF-related apoptosis-inducing ligand (TRAIL) that them to directly kill virus-infected cells. Following a systemic virus infection the CD8 T cell response is primed within secondary lymphoid organs, such as the spleen and lymph nodes (LNs). Although, it has ...


Natural Killer Cell Activation, Trafficking, And Contribution To Immune Responses To Viral Pathogens, Lindsey Elizabeth Carlin Jul 2013

Natural Killer Cell Activation, Trafficking, And Contribution To Immune Responses To Viral Pathogens, Lindsey Elizabeth Carlin

Theses and Dissertations

Natural killer (NK) cells are a critical component of the immune response against viral infections. NK cell depletion prior to murine cytomegalovirus (MCMV) infections results in increased susceptibility to infection in several mouse strains. The mechanism of protection in C57Bl/6 mice is dependent on the activation of NK cells by Ly49H recognition of m157. Our previous studies have examined important residues of m157 for Ly49H recognition, as well as the contribution of m157 glycosylation to NK cell activation. However, what role the glycophosphatidyl inositol (GPI) anchor of m157 plays in Ly49H activation was unknown. Here we demonstrate that the ...


Modulating Influenza And Heparin Binding Viruses’ Pathogenesis With Extrinsic Receptor Decoy Liposomes: A Dissertation, Gabriel L. Hendricks Jun 2013

Modulating Influenza And Heparin Binding Viruses’ Pathogenesis With Extrinsic Receptor Decoy Liposomes: A Dissertation, Gabriel L. Hendricks

GSBS Dissertations and Theses

Influenza is a severe disease in humans and animals, causing upwards of 40,000 deaths every year in America alone. Influenza A virus (IAV) also causes periodic pandemics every 10 to 50 years, killing millions of people. Despite this, very few effective therapies are available. All strains of IAV are prone to developing resistance to antibodies due to the high mutation rate in the viral genome. Because of this mutation rate, a yearly vaccine must be generated before every flu season, and efficacy varies year to year. IAV has also mutated to escape several of the clinically-approved small molecule inhibitors ...


Human Adenovirus E1a Binds And Retasks Cellular Hbre1, Blocking Interferon Signalling And Activating Virus Early Gene Transcription, Gregory J. Fonseca Jun 2013

Human Adenovirus E1a Binds And Retasks Cellular Hbre1, Blocking Interferon Signalling And Activating Virus Early Gene Transcription, Gregory J. Fonseca

Electronic Thesis and Dissertation Repository

Upon infection, human adenovirus (HAdV) must block interferon signaling and activate the expression of its early genes to reprogram the cellular environment to support virus replication. During the initial phase of infection, these processes are orchestrated by the first HAdV gene expressed during infection, early region 1A (E1A). E1A binds and appropriates components of the cellular transcriptional machinery to modulate cellular gene transcription and activate viral early genes transcription. We have identified hBre1/RNF20 as a novel target of E1A. hBre1 is an E3 ubiquitin ligase which acts with the Ube2b E2 conjugase and accessory factors RNF40 and WAC1 to ...


The Effects Of Soil Ph And Composition On Blacklegged Tick Molting Success Avian Window Strike Mortality On Union College Campus, Kaleigh Ahern Jun 2013

The Effects Of Soil Ph And Composition On Blacklegged Tick Molting Success Avian Window Strike Mortality On Union College Campus, Kaleigh Ahern

Honors Theses

The blacklegged tick (Ixodes scapularis) is the one of the most significant vectors of infectious disease in the world and most notorious for its ability to transmit Borrelia burgdorferi, the bacteria that causes Lyme disease. Because both the range of the blacklegged tick and the annual incidence of Lyme disease have been increasing in North America over the past several decades, it is becoming increasingly important to better understand how environmental factors contribute to blacklegged tick survival. Past studies have shown that these factors include precipitation levels, extent of groundcover, plant and animal community composition, temperature, and soil type. Because ...