Immunology and Infectious Disease Commons^™

A One Health Approach To Enhancing Sars-Cov-2 Surveillance, Lauren C. Cybulska

Dissertations and Theses

Background

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus that causes coronavirus disease-2019 (COVID-19) in humans, can also infect domestic dogs (Canis lupus familiaris) and cats (Felis catus). Susceptibility and viral transmissibility in these species are concerns for public health due to the spillover risk to humans or other animals. This dissertation uses a One Health framework to explore key issues on this topic. We aim to identify gaps in understanding of SARS-CoV-2 in companion animals and investigate novel surveillance methods through human, animal, and environmental health perspectives.

Methods

Paper 1 provides an in-depth exploration of …

Characterizing The Role Of The Complement Receptor C3ar In Regulating Inflammatory Responses And Mitochondrial Function In Activated Macrophages, Jesse Alan Corcoran

Dissertations and Theses

The complement system is an integral part of the innate immune response, and consists of a series of proteins that are mostly (although not exclusively) synthesized in the liver that circulate in the plasma as inactive precursors, as well as receptors on the surface of immune cells. In immune cells such as macrophages, recognition of pathogens by Toll-like receptors (TLRs) leads to the initiation of inflammation and triggers complement activation through a coordinated sequential enzyme cascade that results in the production of bioactive C3a, which interacts with membrane-bound receptor C3aR to regulate innate immune cell function and outcome of bacterial …

Targeting Cancers With Ohsv-Based Oncolytic Viral Immunotherapy, Rakin Tammam Nasar, Ifeanyi Kingsley Uche, Konstantin G. Kousoulas

School of Medicine Faculty Publications

The recent success of cancer immunotherapies, such as immune checkpoint inhibitor (ICIs), monoclonal antibodies (mAbs), cancer vaccines, and adoptive cellular therapies (ACTs), has revolutionized traditional cancer treatment. However, these immunotherapeutic modalities have variable efficacies, and many of them exhibit adverse effects. Oncolytic viral Immunotherapy (OViT), whereby viruses are used to directly or indirectly induce anti-cancer immune responses, is emerging as a novel immunotherapy for treating patients with different types of cancer. The herpes simplex virus type-1 (HSV-1) possesses many characteristics that inform its use as an effective OViT agents and remains a leading candidate. Its recent clinical success resulted in …

Fisheries Occasional Publication No.147 - Aquaculture Development Zones – Policy Position Relating To Permitted Alternative Species, Department Of Primary Industries And Regional Development, Western Australia

Fisheries Occasional Publications

The purpose of this policy is to set out considerations relevant to the assessment of aquaculture proposals within Aquaculture Development Zones (ADZ) for species distinct from the group of species for which the ADZ was initially established (Alternative Species).

The Role Of Micrornas On Systemic And Central Nervous System- Inflammation In Aged Mice, Anik Banerjee

Dissertations and Theses (Open Access)

MicroRNAs play a crucial role in multiple biological processes, including development, cell differentiation, proliferation, metabolism, and cell death. Aberrant regulation of microRNAs is seen in many diseases, such as sepsis, cardiovascular disease, neurological diseases such as stroke, and metabolic disorders. Because of their involvement in disease processes, microRNAs have been investigated as both potential biomarkers, and as therapeutic targets. Age-related inflammatory diseases including diabetes, obesity, and atherosclerosis are important risk factors for infection and sepsis. Intestinal barrier impairment occurs with aging and after brain injuries, including stroke. Both aging and stroke increase the risk of infection and sepsis and are …

Targeting Sinonasal Undifferentiated Carcinoma With A Combinatory Immunotherapy Approach, Austin T K Hoke, Yoko Takahashi, Michelle R Padget, Javier Gomez, Moran Amit, Jared Burks, Diana Bell, Tongxin Xie, Patrick Soon-Shiong, James W Hodge, Ehab Y Hanna, Nyall R London

Faculty, Staff and Student Publications

PURPOSE: Sinonasal undifferentiated carcinoma (SNUC) is a rare, aggressive malignancy of the sinonasal cavity with poor prognosis and limited treatment options. To investigate the potential for SNUC sensitivity to combinatory immunotherapy, we performed in vitro studies with SNUC cell lines and used multi-spectral immunofluorescence to characterize the in vivo patient SNUC tumor immune microenvironment (TIME).

EXPERIMENTAL DESIGN: Human-derived SNUC cell lines were used for in vitro studies of tumor cell susceptibility to natural killer (NK) cell-based immunotherapeutic strategies. Tumor samples from 14 treatment naïve SNUC patients were examined via multi-spectral immunofluorescence and clinical correlations assessed.

RESULTS: Anti-PD-L1 blockade enhanced NK …

Immune Responses Of Neonatal (14-Day Old) And Adult (6 Weeks Old) Mice Lung And Spleen Cells To Gamma-Irradiated Mycobacterium Tuberculosis Stimulation, Oyinkansola F. Adeyemi

Biotechnology Theses

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is a global health challenge, especially in vulnerable populations like neonates, whose immune systems are still developing. Understanding the immune responses to Mtb in neonates is critical for the development of better vaccine and treatment strategies. Building upon previous research from our laboratory, which demonstrated that γMtb stimulated neonatal mice (0, 3, and 7 days old) lung cells displayed distinct cytokine profiles and increased expansion of myeloid-derived suppressor cell subpopulations than adult mice lung cells. In the current study, we investigated age-dependent immune responses in 14-day-old (neonates) and 6-week-old (adults) mice. We found …

T-Cell Redirecting Bispecific Antibodies: A Review Of A Novel Class Of Immuno-Oncology For Advanced Prostate Cancer, Julia Palecki, Amman Bhasin, Andrew Bernstein, Patrick Mille, William Tester, William Kelly, Kevin Zarrabi

Kimmel Cancer Center Faculty Papers

Novel T-cell immunotherapies such as bispecific T-cell engagers (BiTEs) are emerging as promising therapeutic strategies for prostate cancer. BiTEs are engineered bispecific antibodies containing two distinct binding domains that allow for concurrent binding to tumor-associated antigens (TAAs) as well as immune effector cells, thus promoting an immune response against cancer cells. Prostate cancer is rich in tumor associated antigens such as, but not limited to, PSMA, PSCA, hK2, and STEAP1 and there is strong biologic rationale for employment of T-cell redirecting BiTEs within the prostate cancer disease space. Early generation BiTE constructs employed in clinical study have demonstrated meaningful antitumor …

Factors Affecting Adherence To Antiretroviral Therapy Among People Living With Hiv/Aids In Antigua And Barbuda, Yuliecia Antoinette Rowe-Harris Mrs, Chirlynor Ebora Calbayan Mrs, Kepha Odiwuor Pondi Mr

Adventist Human-Subject Researchers Association

This study examined factors affecting adherence to antiretroviral therapy (ART) among people living with HIV/AIDS in Antigua and Barbuda. The findings identified multiple variables, emphasizing the dynamic components affecting ART adherence. These findings address a local gap and provide insights into the unique adherence challenges faced by a vulnerable population.

Developing A Membrane-Proximal Cd33-Targeting Car T Cell, Ruby Freeman, Sanam Shahid, Abdul G Khan, Serena C Mathew, Sydney Souness, Erin R Burns, Jasmine S Um, Kento Tanaka, Winson Cai, Sarah Yoo, Andrew Dunbar, Young Park, Devin Mcavoy, Kinga K Hosszu, Ross L Levine, Jaap Jan Boelens, Ivo C Lorenz, Renier J Brentjens, Anthony F Daniyan

Faculty, Staff and Student Publications

BACKGROUND: CD33 is a tractable target in acute myeloid leukemia (AML) for chimeric antigen receptor (CAR) T cell therapy, but clinical success is lacking.

METHODS: We developed 3P14HLh28Z, a novel CD33-directed CD28/CD3Z-based CAR T cell derived from a high-affinity binder obtained through membrane-proximal fragment immunization in humanized mice.

RESULTS: We found that immunization exclusively with the membrane-proximal domain of CD33 is necessary for identification of membrane-proximal binders in humanized mice. Compared with clinically validated lintuzumab-based CAR T cells targeting distal CD33 epitopes, 3P14HLh28Z showed enhanced in vitro functionality as well as superior tumor control and increased overall survival in both …

Reassignment Of Some Caryospora Species (Apicomplexa: Eimeriidae) To Eumonospora (Apicomplexa: Sarcocystidae) And A Summary, Donald W. Duszynski

MANTER: Journal of Parasite Biodiversity

This review was crafted to clear up some of the current confusion regarding the correct taxonomic placement of those apicomplexan coccidians that produce unique monosporocystic octosporozoic (1 sporocyst with 8 sporozoites) oocysts during the sexual phase of their life history in vertebrate hosts. Currently, such oocysts have been placed in 1 of 4 genera, Avispora, Caryospora, Karyospora, or Eumonospora, 2 of which are no longer accepted or useful (Avispora and Karyospora). My review suggests that to present (2023) there are 62 valid Caryospora and 26 valid Eumonospora species. Caryospora species are recorded from a bird …

A Potential Of Watercress Nasturtium Officinale Bioactive Compounds In Inhibiting Infectious Myonecrosis Virus (Imnv) By Targeting Rna-Dependent Rna Polymerase (Rdrp) Virus From Several Countries: In Silico Approach, Qurrota A’Yunin, Fatchiyah Fatchiyah, Maftuch Maftuch, Feri Eko Hermanto, Muhammad Hermawan Widyananda, Narendra Santika Hartana, Muhaimin Rifa’I, Yoga Dwi Jatmiko

Karbala International Journal of Modern Science

Infectious myonecrosis virus (IMNV) disease causes mass mortality and decreased shrimp production. The RdRp region projects to the interior, where it may function in transcription. The focus of this study was to determine the effect of amino acid polymorphisms from several countries on the structure of RdRp and identify the potential of watercress in inhibiting IMNV by targeting the RdRp protein of IMNV through an in silico approach. The results showed that the structure of the IMNV RdRp protein from Indonesia was similar to Mexico, and the protein structure from India_QDN was identical to India_QIL. Ligand binding affinity values showed …

Impact Of Toll-Like Receptor 10 Mutations On Tuberculosis Infections, Adriana Nicole Rafael, Sangman Kim

Master's Theses

Tuberculosis (TB), caused by the intracellular pathogen Mycobacterium tuberculosis (M. tb), is a leading global health crisis causing millions of cases and deaths each year. Though it affects individuals of any race, ethnicity, or cultural group, research shows the disease disproportionately affects individuals with Asian ancestry. Immunity to M. tb starts with its recognition by pattern recognition receptors such as Toll-like receptors (TLRs), which are key players in immune responses. TLR-10, an understudied toll-like receptor due to its inability to be studied through mouse models, is thought to play a key role in the clearance of inflammatory diseases. SNP I775V, …

Mathematical Modeling Suggests Pathways Of Systemic Dissemination Of Mycobacterium Tuberculosis In Mice, Vitaly V. Ganusov

Biology and Medicine Through Mathematics Conference

No abstract provided.

Graphing The Curve: A Mathematical Expedition Into Social Distancing's Role In The South African Covid-19 Narrative, Chidozie Williams Chukwu

Biology and Medicine Through Mathematics Conference

No abstract provided.

Optimizing Immunotherapies For Improved Cancer Treatment, Anne Talkington, Anthony Kearsley

Biology and Medicine Through Mathematics Conference

No abstract provided.

Standard Rodent Diets Differentially Impact Alcohol Consumption, Preference, And Gut Microbiome Diversity, Aline Zaparte, Evan Dore, Selby White, Franciely Paliarin, Cameron Gabriel, Katherine Copenhaver, Samhita Basavanhalli, Emily Garcia, Rishith Vaddavalli, Meng Luo, Christopher M. Taylor, David Allen Welsh, Rajani Maiya

School of Graduate Studies Faculty Publications

Alcohol use disorder (AUD) is a complex and widespread disease with limited pharmacotherapies. Preclinical animal models of AUD use a variety of voluntary alcohol consumption procedures to recapitulate different phases of AUD, including binge alcohol consumption and dependence. However, voluntary alcohol consumption in mice is widely variable, making it difficult to reproduce results across labs. Accumulating evidence indicates that different brands of commercially available rodent chow can profoundly influence alcohol intake. In this study, we investigated the effects of three commercially available and widely used rodent diet formulations on alcohol consumption and preference in C57BL/6 J mice using the 24 …

Omani Camels From A Cultural And Genomics Perspective, Al Muatasim Al Zadjali

Electronic Theses and Dissertations

The Dromedarian camel, Camelus dromedarius, is native to the Arabian Peninsula, including the Sultanate of Oman. These camels are used for food, milk, as well as show and racing competitions. Despite their economic and cultural importance research on camels in Oman is limited. The goal of this study was to examine their genomic variation, relationship with camels in other parts of the Arabian Peninsula, and to determine if selective breeding has led to the establishment of distinct breeds in Oman. Information was compiled from multiple sources to produce a comprehensive review on the breeding, management, economic and cultural use, …

New Insights Into T Lymphocyte-Mediated Immunity To Toxoplasma Gondii, Claire Marie Doherty

Biology ETDs

With nearly a third of the global population infected with the protozoan, Toxoplasma gondii, this parasite sits at a unique, immune-mediated interface of health and disease. In healthy individuals, Toxoplasma results in a chronic yet asymptomatic infection of the central nervous system. This quiescent infection is the result of parasite exploitation of host immune barriers, yet Toxoplasma can quickly become an opportunistic pathogen when immunity is disrupted by illness or immunosuppressive therapies. During the HIV-AIDS pandemic, it was observed that once latent Toxoplasma infections became the cause of severe, even fatal, disease in the absence of an intact T …

Immunopathogenesis Of Post-Infectious Hydrocephalus, Sascha Powers Bernier

Honors Scholar Theses

Hydrocephalus is characterized by the abnormal accumulation of cerebrospinal fluid (CSF) within the brain ventricles. In post-infectious hydrocephalus (PIH) cases, the condition presents challenges in understanding the immune response. PIH is a complex condition, often persisting after the initial infection is treated and thus requiring a deeper understanding of the immune mechanisms involved in its development. This thesis will explore the immunopathogenesis of PIH, elucidating the relationship between the immune response and neurological complications that would succeed infection. The immune response of PIH includes a series of events, beginning with the activation of immune cells and finishing with the release …

Correction: Horne Et Al White Matter Correlates Of Domain-Specific Working Memory, Autumn Horne, Junhua Ding, Tatiana T Schnur, Randi C Martin

Faculty, Staff and Student Publications

In the original publication [...].

Serine Deamination By Human Serine Racemase Synergizes With Antibiotics To Curtail The Replication Of Chlamydia Trachomatis, Patricia D. Mott, Arnold H. Zea, Jamiya Lewis, Oygul Mirzalieva, Ashok A. Aiyar

School of Medicine Faculty Publications

The obligate intracellular bacterium, Chlamydia trachomatis, has evolved to depend on its human host for many metabolites, including most amino acids and three of the four nucleotides. Given this, it is not surprising that depletion of a single amino acid in the host cell growth medium blocks chlamydial replication. Paradoxically, supra-normal levels of some amino acids also block productive replication of Chlamydia. Here, we have determined how elevated serine levels, generated by exogenous supplementation, impede chlamydial inclusion development and reduce the generation of infectious progeny. Our findings reveal that human serine racemase, which is broadly expressed in multiple tissues, potentiates …

Pharmacodynamic Effects Of Zsj-0228 On Complement Protein Deposition In The Kidneys Of Focal Segmental Glomerulosclerosis-Afflicted Mice., Braeden Pinkerton

Theses & Dissertations

Chronic inflammation, when left untreated, may result in significant morbidity and in severe cases, mortality. While glucocorticoids (GCs) are still being extensively used clinically as a class of very potent anti-inflammatory agents, they are also notorious for diverse adverse side effects. To mitigate these side effects, we have developed a polyethylene glycol (PEG)-based prodrug (ZSJ-0228) of dexamethasone (Dex). When tested on rodent models of Lupus Nephritis and Focal Segmental Glomerulosclerosis (FSGS), ZSJ-0228 was found to provide potent and sustained therapeutic efficacy without any detectable typical GC-associated side effects. Given ZSJ-0228’s transient renal exposure after systemic administration, it is yet to …

Mucins: Drivers Of Cancer Cell And Microenvironment Crosstalk In Pancreatic Cancer, Xiaoqi Li

Theses & Dissertations

Mucins facilitate the pancreatic cancer (PC) initiation, progression, and metastasis. Among mucins, MUC4 has been reported to inhibit lymphokine-activated cell killing and induce the apoptosis of cytotoxic T-cells. Counterintuitively, MUC4 expression is upregulated by multiple T-cell-secreted cytokines, such as IFN-γ, IL-17, and stroma-secreted factors like retinoic acid. Previously, we have identified that nuclear receptor coactivator 3 (NCOA3) regulates the MUC1 and MUC4 expression by increasing chromatin accessibility and maintaining protein stability. However, the comprehensive crosstalk mediated by MUC4 in cancer cells and T-cells and how its upstream regulator, NCOA3, modifies the cancer cell-intrinsic behavior is still elusive. Here, we show …

The Physiological Significance Of Nitric Oxide Synthase In Staphylococci, Ryan M. Singh

Theses & Dissertations

Staphylococci, particularly Staphylococcus epidermidis, are common causes of implant-associated infections that may result in notable morbidity and mortality. One of the ways the innate immune system attempts to combat these invading pathogens is via the respiratory burst, in which free radical species such as nitric oxide (NO^•), toxic to bacterial respiration, are released in large quantities. Despite the toxicity of NO^•, some bacteria, including staphylococci, encode an endogenous bacterial nitric oxide synthase (bNOS), whose physiological role has been unclear until now. In this dissertation, we demonstrate that S. epidermidis is able to overcome the toxicity …

Therapeutic Effects Of Bet Protein Inhibition In B-Cell Malignancies And Beyond, Audrey L. Smith

Theses & Dissertations

Chronic lymphocytic leukemia (CLL) develops through a combination of intrinsic genetic defects, constitutively active survival/proliferation signaling pathways, and complex microenvironment interactions. Redundant tumor microenvironment (TME) immuno-suppressive mechanisms and epigenetic maintenance of terminal T-cell dysfunction also greatly hinder anti-tumor T-cell responses in CLL. Small-molecule agents targeting the B-cell receptor (BCR) pathway and anti-apoptotic proteins alone or in combination with chemo-immunotherapy have revolutionized the management of CLL, yet there is still a significant need for novel therapeutic strategies to yield durable tumor elimination. Bromodomain and extra-terminal domain (BET) proteins are epigenetic readers that bind to acetyl-lysine residues on histones to regulate gene …

Kras G12c Inhibitor Combination Therapies: Current Evidence And Challenge, Hirotaka Miyashita, Shumei Kato, David S Hong

Faculty, Staff and Student Publications

Although KRAS G12C inhibitors have proven that KRAS is a "druggable" target of cancer, KRAS G12C inhibitor monotherapies have demonstrated limited clinical efficacy due to primary and acquired resistance mechanisms. Multiple combinations of KRAS G12C inhibitors with other targeted therapies, such as RTK, SHP2, and MEK inhibitors, have been investigated in clinical trials to overcome the resistance. They have demonstrated promising efficacy especially by combining KRAS G12C and EGFR inhibitors for KRAS G12C-mutated colorectal cancer. Many clinical trials of combinations of KRAS G12C inhibitors with other targeted therapies, such as SOS1, ERK, CDK4/6, and wild-type RAS, are ongoing. Furthermore, preclinical …

Isolation Of Aged Mouse Primary Microglia As A Model System For Alzheimer’S Disease Research, Michael Landis

Biology Honors Papers

Microglia and their role as the immune cells of the central nervous system are an emerging area of interest within Alzheimer’s research, particularly as they have shown in a benevolent and malevolent cellular context. Models of Alzheimer’s disease are very light in studying microglia, so in this study a model of microglia isolated from aged mice is established in order to study the phagocytic activity and protein expression of microglia in response to Amyloid Beta. The cells were isolated from aged mice and cultured before being used to confirm cellular identity, as well as to measure phagocytic activity. This study …

Investigation Of Avaren-Fc's Therapeutic Potential Against Ovarian Cancer., Katarina Lee Mayer

Electronic Theses and Dissertations

This thesis describes the investigation of Avaren-Fc (AvFc), a novel lectin-based therapeutic fusion protein consisting of the recombinant Avaren lectin and the Fc region of human IgG1, against ovarian cancer. AvFc possesses selectivity toward tumor associated N-linked high-mannose-type glycans. The present study demonstrates AvFc’s in vitro activity against OVCA cell lines via antibody-dependent cell-mediated cytotoxicity and its ability to extend the survival of mice challenged with murine ID8 OVCA cells after repeated systemic administration. Furthermore, AvFc treatment in this model was found to increase the presence of peritoneal leukocytes, suggesting a shift toward an improved antitumor immune response. Another key …

Porphyromonas Gingivalis Inactivates Anti-Viral Immunity At The Oral And Respiratory Epithelium., Carlos J. Rodriguez Hernandez

Electronic Theses and Dissertations

The host microbiome plays an important role in fine-tuning host immune responses in a manner that ultimately impacts outcomes in viral infection. Symbiotic relationships between commensal bacteria and host epithelial and immune cells prime interferon (IFN) signaling, modulating the nature and intensity of the immune response to viral infections at mucosal barrier surfaces. In this doctoral thesis, I explore how dysbiotic shifts in the oral microbial communities modulate antiviral responses at the oral and oro-respiratory mucosal barriers. I identified that in response to a viral challenge, gingival epithelial cells (GECs) preferentially induced type III IFNs (IFN-λ), a newly described family …