Life Sciences Commons^™

The Regulation Of Autoimmunity Genes In Pancreatic Β-Cells By Nf-Κb, Thomas Malone Martin

LSU Doctoral Dissertations

Type 1 diabetes (T1D) is an autoimmune disease where the immune system targets the pancreatic islet beta-cells, which are responsible for insulin production and secretion, leading to a state of insulin insufficiency. Many of the molecular details of disease onset and progression remain poorly understood, including key aspects of cytokine signaling. Therefore, we have examined some of the consequences of inflammatory cytokine signaling as a critical module relevant to T1D. Using interleukin-1 (IL-1) signaling as a well-defined paradigm for inflammation, we investigated key components of this signaling pathway in pancreatic beta-cells. We identified ICAM-1, one of the proteins expressed in …

The Impacts Of Immune Challenges On Fish Behavior And Physiology, Teisha King

LSU Doctoral Dissertations

For species living in dominance hierarchies, social rank dictates access to resources and often contributes to reproductive success. To ensure survival, individuals constantly evaluate trade- offs between crucial biological systems, like the reproductive and immune systems, depending on their social rank and physiological state. Little is known about how social species balance interactions between immune system function, fluctuations in social status and reproductive fitness, and the performance of behaviors necessary for maintaining social status when sick, particularly in fishes, the largest and most diverse group of vertebrates. My dissertation research uses a whole animal approach to examine how physiological profiles …

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 …

The Herpes Simplex Virus Type-1 (Hsv-1), Vc2 Live-Attenuated Vaccine Strain Induces Robust Antitumor Immune Responses And Ameliorates Intra-Tumor Immunosuppression In An Immunocompetent B16f10-Derived Murine Melanoma Model, Ifeanyi Kingsley Uche

LSU Doctoral Dissertations

Current cancer immunotherapies include immune checkpoint inhibitors, adoptive cellular therapy, and cancer vaccines. While some of these therapies have met with great clinical success, they are associated with several limitations. Oncolytic virotherapy (OVT) has emerged as a bonafide promising immunotherapy, that uses viral infection to liberate tumor antigens in an immunogenic context to promote the development of anti-tumor immune responses. At present, Talimogene laherparepvec (T-VEC; Imlygic™), a modified type 1 herpes simplex virus (HSV-1) is the only FDA approved OVT for human cancer treatment (melanoma). While T-VEC is associated with limited response rates, its modest efficacy supports the continued development …

Establishing And Validating Methods To Assess The Influence Of Exercise On Circulating Exosome Profiles In Sedentary Older Adults, Heather Quiriarte

LSU Master's Theses

Aging is associated with progressing cellular structural and functional changes, and sedentary behavior can exacerbate these hallmarks of aging. Routine exercise is known to have beneficial effects on physiological systems, but the exact molecular mechanisms behind the health benefits are unclear. Emerging evidence suggests extracellular vesicles called exosomes are involved in the intercommunication between cells and organs following exercise by delivering their cargo such as proteins and miRNAs. miRNA profiles in older adults following acute and chronic exercise need further exploration. Specifically, the effects of regular low-intensity physical activity (LPA) breaks in sedentary time on proteins and miRNA packaged in …

Immune Gene Diversity And Populations Structure Of Reticulated Flatwoods Salamander (Ambystoma Bishopi), Steven Tyler Williams

LSU Master's Theses

Reticulated flatwoods salamander (Ambystoma bishopi) populations began decreasing dramatically in the late 1900s. Contemporary populations are small, isolated, and may be susceptible to inbreeding and reduced adaptive potential because of low genetic variation. Genetic variation at immune genes is especially important as it influences disease susceptibility and adaptation to emerging infectious pathogens, a central conservation concern for declining amphibians. Connectivity between isolated populations is also vital to maintain genetic diversity and avoid inbreeding. I collected tissue samples from across the extant range of this salamander to examine genetic variation and population structure in: immune genes broadly (immunome), the …

Mechanism Of Neutrophil Homeostasis And Immunity In Pneumonia And Sepsis, Sagar Paudel

LSU Doctoral Dissertations

Severe bacterial pneumonia and septicemia are pressing health problems. A better understanding of cellular and molecular players of neutrophil immunity and homeostasis in bacterial pneumonia and sepsis is critical for inspiring novel therapeutics. Chemokine CXCL1 is a widely secreted neutrophil attractant and Nod-like receptor (NLRC4) is commonly expressed cytoplasmic pathogen sensor in hematopoietic compartments. How these innate mediators convert pathogen signals into molecular cues of immune response in context of Gram-positive bacterial pneumonia and septicemia largely remain unknown. Utilizing Cxcl1 gene deficient mice, we demonstrate CXCL1 regulates neutrophil influx, bacterial clearance, and host survival in pneumococcal pneumonia-derived sepsis. Furthermore, Cxcl1 …

Nlrp6 In Gram-Positive Pneumonia And Sepsis, Laxman Ghimire

LSU Doctoral Dissertations

Acute lower respiratory infections (pneumonia) and pneumonia-derived sepsis are among the leading causes of death in the world causing 7.8 million deaths annually. In this regard, Methicillin-resistant Staphylococcus aureus (MRSA) is endemic in the US and implicated for causing high mortality-associated necrotizing pneumonia and aggravating viral pneumonia with superinfection. Additionally, sepsis is the 7^th leading cause of death among newborns in the US and is responsible for more than 750,000 hospitalization cases every year. Although there is a plethora of research in both pneumonia and sepsis, the detailed pathophysiology still remains elusive. Understanding the host defense mechanism will help …

The Use Of Geospatial Modeling And Novel Diagnostics To Detect And Map Risk Factors Of Soil-Transmitted Helminths In Feira De Santana, Brazil, Ryan Harry Avery

LSU Doctoral Dissertations

Soil-transmitted helminth (STH) infections impact billions of people worldwide. The traditional STH control approach is a morbidity control strategy implementing mass drug administration (MDA) programs targeting school-aged children (SAC). In Brazil, this control strategy has decreased STH prevalence to less than 20% in most of the country and providing an opportunity to transition from the morbidity control program and towards a surveillance and response system geared towards STH elimination. Surveillance and response systems geared towards elimination require the implementation higher accuracy diagnostics to detect infection in low-transmission communities, surveillance of entire households, high-resolution modeling at the household-habitat scale, and targeted …

A Case-Study Approach To Investigate Transmission, Co-Infection, And Clinical Sequelae During Epidemics Of Dengue And Ebola Virus Disease, Jennifer Elizabeth Giovanni

LSU Doctoral Dissertations

From within their ecologic niches, zoonotic viruses emerge from animal reservoirs into the edges and centers of human habitation to exploit opportunities for unabated transmission within immunologically–naïve populations. Our understanding of where, in whom, and how these viruses emerge is under direct challenge, driving the evolution of modern infectious disease epidemiology within a rapidly-connected global community. The studies presented herein are based on analyses of both aggregate and case-level data, which, we argue, provide unique insight into the complexities of transmission, co-infection, and clinical sequelae occurring within, and arising from, epidemics of emerging zoonotic viruses. In Chapter II, we investigate …

Evaluation Of Oncolytic And Immunomodulatory Potential Of The Hsv-1 Live-Attenuated Vaccine Strain Vc2 In An Immunocompetent Murine Melanoma Model, Natalie Wall Fowlkes

LSU Doctoral Dissertations

Melanoma accounts for 90% of skin cancer-related deaths in humans. Treatment options for metastatic melanoma in people is very limited. Melanoma is considered to be an immunogenic tumor, spurring interest in development of immunotherapies for the treatment of metastatic melanoma. Oncolytic virotherapy has been widely investigated. The first ever oncolytic virotherapy to receive FDA-approval is an HSV-1-based virus (Talimogene Laherperavec (T-Vec) or Imlygic) containing a transgene for human GM-CSF to enhance anti-tumor immune responses after injection. Durable response rate in human patients was only 16% despite impressive efficacy in anti-tumor effects in vitro and in murine tumor models. Novel viruses …

Role Of Neutrophils In The Modulation Of Host Responses To Human Respiratory Pneumovirus Infection, Nagarjuna Reddy Cheemarla

LSU Doctoral Dissertations

Neutrophils are the most abundant leukocytes (50% to 70%) in humans and are the first immune cell population recruited to the sites of infection. They are known to act as the first line of innate immune defense against invading pathogens, and more recently, to playing a crucial role in orchestrating adaptive immune responses. The role of neutrophils in the respiratory viral infections till date remains unclear and controversial. Previous studies demonstrated both beneficial as well as pathogenic role for neutrophils in respiratory viral infections, especially influenza.

Previous findings reported an early and high influx of neutrophils into the airways early …

Paclitaxel Enhances Oncolytic Potential Of Herpes Simplex Virus Type-1 In Cancer Cells, Misagh Naderi

LSU Master's Theses

Taxanes are spindle poisons that bind to and stabilize microtubules resulting in mitotic arrest. Herpes simplex Typ-1 (HSV-1) virions utilize the microtubular network for intracellular transport during both virus entry and virus egress from infected cells. It has been reported previously that taxanes may synergize with oncolytic herpes simplex viruses in the treatment of experimental prostate and breast tumors in mice. Other reports have indicated that taxanes may inhibit viral replication in infected cells. In this study the previously characterized Oncolytic Herpes Simplex Virus type 1 (OSVP), which was constructed in Kousoulas lab was used in conjugation with paclitaxel (taxol) …

Characterization Of The Interaction Between R. Conorii And Human Host Vitronectin In Rickettsial Pathogenesis, Abigail Inez Fish

LSU Doctoral Dissertations

Spotted Fever Group Rickettsia are inoculated into the mammalian host during hematophagous arthropod feeding. Once in the bloodstream and during dissemination, the survival of these pathogens is dependent upon their ability to evade innate host defenses until a proper cellular target is reached. The establishment of a successful infection also relies on the ability of the bacteria to attach and invade target cells, as failure to do so results in destruction of the bacterium. Rickettsia conorii expresses an outer membrane protein, Adr1, which binds the multifunctional human glycoprotein, vitronectin, to promote resistance to complement mediated killing. Homologs of Adr1 are …

Role Of Mucin 19 In The Respiratory Tract, Kaitlin Mcbride

LSU Master's Theses

Human metapneumovirus (HMPV) is a negative sense, single stranded RNA virus belonging to the Pneumoviridae family, and represents an important pathogen that causes severe respiratory disease worldwide. There is currently no vaccine against HMPV, so it is important to study the aspects of the immune response induced by HMPV. Because infiltration of mucus is a hallmark of HMPV infection, it is warranted to study the role of mucus in the disease process. Mucin proteins make up the major component of mucus and can be found within the airway and lungs. Previous work from our laboratory demonstrated a high upregulation of …

5-Lipoxygenase (5-Lox)-5-Lipoxygenase Activating Protein (Flap)-Nanodisc Complex: A Model For The 5-Lox-Flap Interaction, Erin Elizabeth Schexnaydre

LSU Doctoral Dissertations

Leukotrienes (LT) are lipid mediators of the inflammatory response that play important roles in diseases such as asthma and atherosclerosis. Leukotriene A4 (LTA₄) is synthesized from arachidonic acid (AA) by 5-lipoxygenase (5-LOX) with the help of 5-lipoxygenase activating protein (FLAP), a trimeric nuclear transmembrane protein. Exactly how 5-LOX and FLAP interact is not well understood, however FLAP is essential for the production of leukotrienes in vivo. I used nanodiscs (NDs), engineered membrane systems, as a tool to study the 5-LOX-FLAP interaction. FLAP was incorporated into NDs with a phospholipid composition to mimic of the nuclear membrane. Structural features …