Life Sciences Commons^™

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 …