Life Sciences Commons^™

Pulsed Electric Fields Sensitize Methicillin-Resistant Staphylococcus Aureus To Antibacterial Therapies And Stimulate Host Immune Responses, Alexandra E. Chittams-Miles

Biomedical Sciences Theses & Dissertations

This research explores the impact of nanosecond pulsed electric fields (nsPEF) on two fronts: their immune stimulatory effects and their potential as a novel strategy to enhance the sensitivity of Methicillin-resistant Staphylococcus aureus (MRSA) to clinically relevant antibiotics. While pulsed electric fields have been reported to have an immune stimulatory effect, the mechanisms responsible for these effects have yet to be determined.

Our investigation addresses the rising concern of MRSA derived skin and soft tissue infections (SSTIs). Consistent with other publications, we found that nsPEF alone cause modest inactivation of planktonic MRSA. We then investigated the effects of nsPEF in …

The Investigations Of Nps Modulated Immunity And Immunometabolism, Brittney Leigh Ruedlinger

Biomedical Sciences Theses & Dissertations

Cancers remain in the top noncommunicable diseases responsible for premature mortality. The heterogeneity among cancers and within tumors makes treating them ever more challenging. Our misfortune for developing cures is mocked by cancer, with the lowest probability of success (PoS) through clinical trials and FDA approval. At the basic level, there are generally two broad gaps impeding cancer eradication: the unidentified shared mechanism(s) exploited by all cancers and the therapeutic approach to intervene. Nanosecond pulse stimulation (NPS) offers a unique approach since its broad impacts intersect those often hijacked by oncogenesis. Metabolic pathways, known for dysfunctions among cancers, share a …

The Impact Of Nanopulse Treatment On The Tumor Microenvironment In Breast Cancer: Overturning The Treg Immunosuppressive Dominance, Anthony Nanajian

Biomedical Sciences Theses & Dissertations

Nanopulse treatment (NPT) is a high-power electric engineering modality that has been shown to be an effective local tumor treatment approach in multiple cancer models. Our previous studies on the orthotopic 4T1-luc breast cancer model demonstrated that NPT ablated local tumors. The treatment consequently conferred protection against a second live tumor challenge and minimized spontaneous metastasis. This study aims to understand how NPT mounts a potent immune response in a predominantly immunosuppressive tumor.

NPT changed the local and systemic dynamics of immunosuppressive cells by significantly reducing the numbers of regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages …

Anaplasma Phagocytophilum Modulates Mammalian And Arthropod Signaling For Its Survival And Transmission, Supreet Khanal

Biomedical Sciences Theses & Dissertations

Vector-borne diseases (VBDs) are illnesses transmitted to humans and other animals by arthropods such as ticks, mosquitoes, and fleas. These arthropod vectors transmit infectious pathogens such as viruses, bacteria, and protozoa, to humans during blood-feeding. We have very few control strategies to treat or control these diseases. Human anaplasmosis, caused by the bacterium Anaplasma phagocytophilum, is the second most common tick-borne disease in the United States. This work defines three studies elucidating Anaplasma phagocytophilum-mediated modulation of cell signaling in mammalian cells and arthropod vector Ixodes scapularis ticks.

The first study focused on mammalian PI3 kinases signaling in regulating …

Moderate Heat-Assisted Gene Electrotransfer For Intradermal Dna Vaccination And Protein Replacement Therapy In The Skin, Chelsea Marie Edelblute

Biomedical Sciences Theses & Dissertations

Gene electrotransfer (GET) holds great promise for the delivery of therapeutic agents. The skin serves as an attractive target for GET due to its availability and unique cellular composition. Protein replacement therapy and DNA vaccination are potential applications for intradermal GET. The combination of moderate tissue preheating and GET has been shown to achieve elevated gene expression levels while reducing the necessary applied voltage. In the current work, we utilized a 16-pin multi-electrode array (MEA) and incorporated nine optical fibers, connected to an infrared laser, to pre-heat the tissue to 43°C before application of GET. In a guinea pig model, …

Drivers Of Rickettsial Pathogen Transmission And Spillover In Local Tick Populations In Southeastern Virginia, Alexandra Cumbie

Biomedical Sciences Theses & Dissertations

Cases of spotted fever group rickettsiosis are becoming more prevalent in the United States. In Virginia, there are three human-biting ticks which are largely responsible for the spread of rickettsial pathogens and the increase in disease cases. These species include Dermacentor variabilis, Amblyomma americanum, and Amblyomma maculatum; all of which are vectors of rickettsial agents to vertebrate hosts. These species are sympatric as adults and have the potential to share large and small mammal hosts. Their interactions on and off host and their associated rickettsiae were the focus of this dissertation work. Amblyomma americanum is the vector …

Exosomes In Transmission And Blocking Of Arthropod-Borne Flaviviral Infection And Pathogenesis, Wenshuo Zhou

Biomedical Sciences Theses & Dissertations

Vector-borne diseases (VBDs) are human illnesses that are transmitted by vectors such as ticks, mosquitoes, and fleas. These arthropods transmit infectious pathogens such as viruses, protozoa, and bacteria, to humans during their blood-feeding. According to the estimation of the WHO, billions of people are affected by VBDs worldwide, and about 700,000 deaths are reported annually. Currently, very few reliable VBDs control approaches and vaccines available to treat various VBDs. Additionally, approaches to control arthropod’ proliferation and migration are difficult to develop. Furthermore, molecular determinants and mechanisms for the transmission are poorly understood. This work describes two studies identifying the novel …

Olfactory Behavioral Responses Of Mosquito Vectors To Select Attractants And Floral Scents As Related To Circadian Rhythms And Photoperiod Regimes, Bernadette A. Ferraro

Biomedical Sciences Theses & Dissertations

This dissertation discusses mosquito behavioral activities involving circadian rhythms defined as insect sensitivity to select of chemical volatiles that vary throughout the 24-hour day. Circannual rhythms occur over seasons varying in photoperiod, defined as the seasonal cycle of light and darkness. These cycles can be endogenously controlled by circadian clocks. The impetus for this research was initiated when reading about the neglected temporal dimension in the context of insect chemical ecology, including insect olfaction. It was proposed that sensitivity to odors does not change in general, but specific sensitivities could vary according to time of day. Chemical scents emitted by …

Targeting The Pin Domain Of Type Ii Toxins Is A Novel Approach To Treat Infections Caused By Nontypeable Haemophilus Influenzae, Ashley Lynne Molinaro

Biomedical Sciences Theses & Dissertations

Toxin-antitoxin (TA) gene pairs have been identified in nearly all bacterial genomes sequenced to date and are thought to facilitate persistence and antibiotic tolerance. TA loci are classified into various types based upon the characteristics of their antitoxins, with those in type II expressing proteic antitoxins. Many toxins from type II modules are ribonucleases that maintain a PilT N-terminus (PIN) domain containing conserved amino acids considered essential for activity. The vapBC (virulence associated protein) TA system is the largest subfamily in this class and has been linked to pathogenesis of nontypeable Haemophilus influenzae (NTHi). This dissertation presents three studies investigating …

Arthropod Organic Anion Transporting Polypeptides In Tick-Borne Bacterial And Viral Infections, Vikas Kumar Taank

Biomedical Sciences Theses & Dissertations

Vector-borne diseases (VBDs) are human illness transmitted by an arthropod vector. World Health Organization (WHO) estimates that VBD has a huge impact worldwide that is responsible for affecting a billion people and causes 700,000 deaths annually. In recent years, there has been a continuous increase in the incidences of tick-borne diseases such as Lyme diseases and human anaplasmosis as reported by Center for Disease Control and Prevention. Very few reliable VBD control strategies have emerged till now. Transmission-blocking vaccines can provide effective management of VBDs but requires identification and characterization of novel vector-pathogen conserved molecules that play a significant role …