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The Development Of A New Pertussis Booster Formulation Via The Implementation Of New Adjuvants And Utilization Of Alternate Routes Of Administration, Megan Ashley Dejong

Graduate Theses, Dissertations, and Problem Reports (ETD)

Pertussis (whooping cough) is a respiratory disease caused by airborne transmission of the Gram-negative bacterium, Bordetella pertussis. Prior to the development of the first pertussis vaccines (whole cell (wP) vaccines), the incidence of pertussis was in the hundreds of thousands of cases per year, which led to the death of many children, as the infection is most severe in younger populations. Thankfully, the wP formulation resulted in a dramatic decrease in the number of annual pertussis cases, nearly eradicating the disease. However, as wP contained the whole B. pertussis bacterium (and its lipooligosaccharide (LOS)), reactogenicity issues became apparent, leading …

Emerging Challenges To Cellular Therapy Of Cancer, Premal D Lulla, Malcolm Brenner

Faculty, Staff and Students Publications

Cellular immunotherapy of cancer in the form of chimeric antigen receptor-modified T-cell therapy has become a standard treatment for lymphoid and more recently plasma cell malignancies. Although their successes in these cancers represent a breakthrough for adoptive cell therapy, there are several challenges to their continued growth in the field of cancer medicine. In this review, we discuss the progress made thus far toward achieving "off-the-shelf" accessibility of cell therapies that has the potential to greatly offset the costs associated with the current practice of making patient-specific products. We also review the innovations under investigation that attempt to make cellular …

Deciphering The Role Of Qpctl In Glioma Progression And Cancer Immunotherapy, Yu'e Liu, Shaojuan Lu, Yihong Sun, Fei Wang, Shibo Yu, Xi Chen, Lei-Lei Wu, Hui Yang, Yufeng Shi, Kaijun Zhao

Faculty, Staff and Students Publications

BACKGROUND: Glioma is the most lethal and most aggressive brain cancer, and currently there is no effective treatment. Cancer immunotherapy is an advanced therapy by manipulating immune cells to attack cancer cells and it has been studied a lot in glioma treatment. Targeting the immune checkpoint CD47 or blocking the CD47-SIRPα axis can effectively eliminate glioma cancer cells but also brings side effects such as anemia. Glutaminyl-peptide cyclotransferase-like protein (QPCTL) catalyzes the pyroglutamylation of CD47 and is crucial for the binding between CD47 and SIRPα. Further study found that loss of intracellular QPCTL limits chemokine function and reshapes myeloid infiltration …

Growth And Differentiation Factor 15 (Gdf15) Levels Predict Adverse Respiratory Outcomes In Premature Neonates, Faeq Almudares, Joseph Hagan, Xinpu Chen, Sridevi Devaraj, Bhagavatula Moorthy, Krithika Lingappan

Faculty, Staff and Students Publications

Growth and differentiation factor 15 (GDF15) is a stress-responsive cytokine, and its expression increases during inflammation, hyperoxia, and senescence. Significantly, GDF15 is secreted by the placenta, and maternal levels increase throughout pregnancy. Serum GDF15 level is a promising biomarker for many lung diseases like pulmonary hypertension and pulmonary fibrosis. However, circulating GDF15 levels in preterm infants and their role as a predictor of respiratory outcomes have not been studied. We hypothesized that GDF15 levels would increase with gestational age at birth, and that postnatal GDF15 will be correlated with adverse respiratory outcomes in preterm infants. Scavenged blood samples were retrieved …

Loss Of Ubiquitin-Specific Peptidase 18 Destabilizes 14-3-3Ζ Protein And Represses Lung Cancer Metastasis, Zibo Chen, Lin Zheng, Yulong Chen, Xiuxia Liu, Masanori Kawakami, Lisa Maria Mustachio, Jason Roszik, Katherine V Ferry-Galow, Ralph E Parchment, Xin Liu, Thorkell Andresson, Gerard Duncan, Jonathan M Kurie, Jaime Rodriguez-Canales, Xi Liu, Ethan Dmitrovsky

Faculty, Staff and Student Publications

Cancer metastasis is a major cause of cancer-related mortality. Strategies to reduce metastases are needed especially in lung cancer, the most common cause of cancer mortality. We previously reported increased ubiquitin-specific peptidase 18 (USP18) expression in lung and other cancers. Engineered reduction of USP18 expression repressed lung cancer growth and promoted apoptosis. This deubiquitinase (DUB) stabilized targeted proteins by removing the complex interferon-stimulated gene 15 (ISG15). This study explores if the loss of USP18 reduced lung cancer metastasis. USP18 knock-down in lung cancer cells was independently achieved using small hairpin RNAs (shRNAs) and small interfering RNAs (siRNAs). USP18 knock-down reduced …

An Emerging Infectious Disease Surveillance Platform For The 21st Century, Eloy Ortiz, Alicia Juarrero

MANTER: Journal of Parasite Biodiversity

Current vector surveillance programs are insufficient for coping with the emerging infectious disease crisis. In particular, current practices do not deploy sufficient information technology (IT) tools to generate actionable insights that can inform interventions and contain and mitigate the spread of vector-borne diseases. VectorAnalytica has developed a highly configurable and adaptable IT platform that imports, harmonizes, and integrates a range of data sources. The state-of-the-art backend development allows users to fully appreciate and understand the complexity of infectious disease dynamics without having to resort to additional statistical and GIS software packages. The platform yields actionable insights into outbreak patterns of …

Let Emerging Plant Diseases Be Predictable, Valeria Trivellone

MANTER: Journal of Parasite Biodiversity

A prevalent concept for colonization and evolution among plant pathogens and their hosts stems from a post-Darwinian paradigm rooted in the formalized assumption of “specialized parasitism.” Seminal studies on rust fungi of socioeconomic importance integrated such an evolutionary perspective driven by the assumption of strict coevolution among pathogens and their plant hosts. Following this fundamentally unfalsifiable assumption, theories regarding host-switching for parasites were dismissed. If colonization occurred, this process would depend upon the origin of specific and novel mutations that allow infections of previously unexploited hosts or host groups, the acquisition of a broader host range. After a specific mutation …

Taking Action: Turning Evolutionary Theory Into Preventive Policies, Orsolya Molnár, Marina Knickel, Christine Marizzi

MANTER: Journal of Parasite Biodiversity

The emerging infectious disease (EID) crisis has been challenging global health security for decades, dealing substantial damage to all socioeconomic landscapes. Control measures have failed to prevent or even mitigate damages from an accelerating wave of EIDs, leading to the emergence and devastation caused by the COVID-19 pandemic. In the wake of the pandemic, we must critically review our public health policies and approaches. Current health security measures are based on the evolutionary theorem of host-parasite coevolution, which falsely deems EIDs as rare and unpredictable. The DAMA protocol (Document, Assess, Monitor, Act) is nested in a novel evolutionary framework that …

The Stockholm Paradigm Explains The Dynamics Of Darwin’S Entangled Bank, Including Emerging Infectious Disease, Salvatore J. Agosta

MANTER: Journal of Parasite Biodiversity

Pathogens and their hosts are embedded within the larger biosphere, what Darwin called the “entangled bank.” Emerging infectious disease occurs when a parasite “switches” to a new host. Understanding the dynamics of emerging disease requires understanding the dynamics of host-switching, which requires a more general understanding of how the biosphere and its constituent members cope when conditions change. The Stockholm paradigm is an integrative evolutionary framework that describes how living systems cope with change by oscillating between exploiting and exploring the geographical and functional dimensions of their environments. It combines organismal capacity, ecological opportunity, and the repeated external perturbations to …

Proximity-Dependent Biotin Labeling In Testicular Germ Cells Identified Tesmin-Associated Proteins, Seiya Oura, Akinori Ninomiya, Fuminori Sugihara, Martin M Matzuk, Masahito Ikawa

Faculty, Staff and Students Publications

Characterization of protein-protein interactions (PPI) is a key to understanding the functions of proteins of interest. Recently developed proximity-dependent biotin identification (BioID) has been actively investigated as an alternative PPI mapping method because of its usefulness in uncovering transient PPI. Here, as an example of proximity labeling proteomics application in the testis, we generated two transgenic mouse lines expressing two biotin ligases (BioID2 or TurboID) fused with TESMIN, which translocates from the cytosol to the nucleus during meiotic progression and is required for reproduction. The BioID2 transgene, albeit not the TurboID transgene, rescued fertility defects of the Tesmin KO male …

Anthelmintic Resistance In Sheep Across Ireland And The Uk: A Literature Review Of The In Vivo Versus In Vitro Methods, Megan Tumulty

SURE Journal: Science Undergraduate Research Experience Journal

Background: The animal welfare and production consequences of gastrointestinal nematode infections, namely Nematodirus battus, on sheep are compelling. The control of gastrointestinal infections has been heavily reliant on the administration of anthelmintics since their introduction into mainstream use in 1960. However, their frequent and often excessive use has resulted in anthelmintic resistance being reported extensively in several gastrointestinal nematode species. The prevalence of anthelmintic resistance as well as the increase in the number of cases of multiple-drug resistance in nematode populations now poses substantial hindrance on the viability of sheep production systems. However, despite the threat N. battus poses …

Knowing The Biosphere: Documentation, Specimens, Archives, And Names Reveal Environmental Change And Emerging Pathogens, Eric P. Hoberg, Valeria Trivellone, Joseph A. Cook, Jonathan L. Dunnum, Walter A. Boeger, Daniel R. Brooks, Salvatore J. Agosta, Jocelyn P. Colella

MANTER: Journal of Parasite Biodiversity

One Health programs and trajectories are now the apparent standard for exploring the occurrence and distribution of emerging pathogens and disease. By definition, One Health has been characterized as a broadly inclusive, collaborative, and transdisciplinary approach with connectivity across local to global scales, which integrates the medical and veterinary community to recognize health outcomes emerging at the environmental nexus for people, animals, plants, and their shared landscapes. One Health has been an incomplete model, conceptually and operationally, focused on reactive and response-based foundations, to limit the impact of emerging pathogens and emerging infectious diseases and, as such, lacks a powerful …

Surveillance Of Antimicrobial Resistance In Veterinary Medicine In The United States: Current Efforts, Challenges, And Opportunities, Juliana M. Ruzante, Beth Harris, Paul Plummer, Raissa R. Raineri, John Dustin Loy, Megan Jacob, Orhan Sahin, Amanda J. Kreuder

School of Veterinary and Biomedical Sciences: Faculty Publications

Antimicrobial resistance (AMR) is a global problem facing human, animal, plant, and environmental health by threatening our ability to effectively treat bacterial infections with antimicrobials. In the United States, robust surveillance efforts exist to collect, analyze, and disseminate AMR data in human health care settings. These tools enable the development of effective infection control methods, the detection of trends, and provide the evidence needed to guide stewardship efforts to reduce the potential for emergence and further spread of AMR. However, in veterinary medicine, there are currently no known equivalent tools. This paper reviews efforts to reduce the potential for emergence …

The Role Of Lncrnas In The Tumor Microenvironment And Immunotherapy Of Melanoma, Wencheng Zhou, Xuewen Xu, Ying Cen, Junjie Chen

Faculty, Staff and Student Publications

Melanoma is one of the most lethal tumors with highly aggressive and metastatic properties. Although immunotherapy and targeted therapy have certain therapeutic effects in melanoma, a significant proportion of patients still have drug resistance after treatment. Recent studies have shown that long noncoding RNAs (lncRNAs) are widely recognized as regulatory factors in cancer. They can regulate numerous cellular processes, including cell proliferation, metastasis, epithelial-mesenchymal transition (EMT) progression and the immune microenvironment. The role of lncRNAs in malignant tumors has received much attention, whereas the relationship between lncRNAs and melanoma requires further investigation. Our review summarizes tumor suppressive and oncogenic lncRNAs …

Crispr Technology As An Antiviral In Dsdna And Ssrna Viruses, Cathryn Mayes

Theses & Dissertations

The COVID-19 pandemic highlights the necessity of emergency response and pandemic preparedness, especially for emerging viral threats. Currently, virus-specific vaccines and antivirals are the primary tools to combat viral diseases; however, broad-spectrum antivirals that target more than one virus species could provide additional protection from emerging and re-emerging viral diseases (Andersen et al. 2020; Zhu et al. 2015; Hickman et al. 2022).

Clustered regulatory interspaced short palindromic repeat (CRISPR)-associated endonucleases have become recently utilized as potential antiviral strategies due to their high specificity, efficacy, and versatility (Najafi et al. 2022). While CRISPR-based antivirals have previously been used to target specific …

Nanofabrication For Precision Vaccinology, Karen Zagorski

Theses & Dissertations

Vaccines are among the most effective and safe therapeutics known to mankind. Historically the approach to the creation of new vaccines has been dominated by empirical research, trial, and error. This thesis focuses on the more modern, rational approaches to vaccinology based on the current understanding of the inner workings of the immune system. We used nanotechnology for the generation of novel immunogens, addressed several challenges, and characterized the immune responses.

The preparation, characterization, and troubleshooting of several vaccines against dimeric amyloid beta are covered in chapters 4-6. Despite being ultimately unsuccessful, this part provided a deeper understanding of the …

The Evolutionary Dynamics Of Infectious Diseases On An Unstable Planet: Insights From Modeling The Stockholm Paradigm, Angie T. C. Souza, Sabrina B. L. Araujo, Walter A. Boeger

MANTER: Journal of Parasite Biodiversity

Emerging infectious diseases (EIDs) are, besides a question of food safety and public health, an ecological and evolutionary issue. The recognition of this condition combined with the accumulation of evidence that pathogens are not specialists in their original hosts evidences the need for understanding how the dynamics of interaction between pathogens and hosts occurs. The Stockholm Paradigm (SP) provides the theoretical fundaments to understand the dynamics of diseases and design proactive measures to avoid the emergence and reemergence of infectious diseases. In this review, we revisit the models that evaluate several aspects of the proposed dynamics of the SP, including …

Single Cell Rna Sequencing Of The Adult Drosophila Eye Reveals Distinct Clusters And Novel Marker Genes For All Major Cell Types, Kelvin Yeung, Komal Kumar Bollepogu Raja, Yoon-Kyung Shim, Yumei Li, Rui Chen, Graeme Mardon

Faculty, Staff and Students Publications

The adult Drosophila eye is a powerful model system for phototransduction and neurodegeneration research. However, single cell resolution transcriptomic data are lacking for this tissue. We present single cell RNA-seq data on 1-day male and female, 3-day and 7-day old male adult eyes, covering early to mature adult eyes. All major cell types, including photoreceptors, cone and pigment cells in the adult eye were captured and identified. Our data sets identified novel cell type specific marker genes, some of which were validated in vivo. R7 and R8 photoreceptors form clusters that reflect their specific Rhodopsin expression and the specific Rhodopsin …

Nucleic Acid Extraction Of Human Immunodeficiency Virus From Municipal Wastewater, Fritz Vanderford, Hayley Baker, Ching-Lan Chang

Undergraduate Research Symposium Lightning Talks

In 2021, globally there were ~ 38.4 million people living with Human immunodeficiency virus (HIV), ~650,000 people died from acquired immunodeficiency syndrome (AIDS) related illnesses, ~1.5 million people acquired HIV. In the US, ~1.9 million people had HIV at the end of 2019, ~30,635 people were diagnosed with HIV in 2020.

Unraveling The Anti-Inflammatory Mechanisms And Efficacy Of Cannabidiol On The Progression Of A Murine Model Of Multiple Sclerosis From The Innate To The Adaptive Immune System To Clinical Symptoms, Christa Marie Frodella

Theses and Dissertations

Cannabidiol (CBD), a non-psychotropic phytocannabinoid with structural similarity to Δ 9 -tetrahydrocannabinol (THC), is currently being investigated as a therapeutic for its immunosuppressive effects. One disease for which CBD is extensively researched is multiple sclerosis (MS), a demyelinating, autoimmune disorder, and its murine model counterpart, experimental autoimmune encephalomyelitis (EAE). The focus of this dissertation aimed to analyze the transcriptomic brain pathways in EAE and its comparison to MS in addition to CBD’s immunosuppressive mechanisms in the innate and adaptive immune systems. Evidence presented here showed that transcriptomic signaling pathways in the EAE brain of mice with clinical symptoms were similar …

Investigating The Involvement Of The Tick Vector In The Induction Of Alpha-Galactose Hypersensitivity (Alpha-Gal Syndrome, Red Meat Allergy) In The United States., Gary Crispell

Dissertations

Alpha-gal syndrome (AGS or sometimes called red meat allergy) is a result of the development of specific IgE antibodies to the oligosaccharide galactose-α-1,3-galactose (α-gal) after a person has had exposure to tick bites. This dissertation investigates four common tick species found in North America: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) for the presence of α-gal by utilizing a combination of immunoproteomic approaches and carbohydrate analysis techniques.

Anti-α-gal IgM antibodies (M86) were used in immunoblotting to detect …

Characterization Of Innate Immune Responses In Mouse Trophoblast Stem Cells And Their Differentiated Cells, Mona Fendereski

Dissertations

The blastocyst is the preimplantation stage embryo consisting of two major components: the inner cell mass (ICM) and the trophectoderm (TE). The ICM forms the fetus, whereas the TE contributes to the placenta development. Previous studies have demonstrated that human and mouse embryonic stem cells (ESCs) derived from the ICM are deficient in expressing type I IFNs in response to viral infection. This study investigated the innate immune responses in mouse trophoblast stem cells (TSCs) and their in vitro differentiated trophoblasts (TSC-TBs). I report that, unlike ESCs, TSCs have a functional IFN system. They can express and respond to type …

Genotype Classification Of Moraxella Bovis Using Maldi-Tof Ms Profiles, Hannah G. Olson, John Dustin Loy, Michael L. Clawson, Emily L. Wynn, Matthew M. Hille

School of Veterinary and Biomedical Sciences: Faculty Publications

Moraxella bovis (M. bovis) is regarded as a causative agent of infectious bovine keratoconjunctivitis (IBK), the most common ocular disease of cattle. Recently, whole genome sequencing identified the presence of two distinct genotypes within M. bovis that differ in chromosome content, potential virulence factors, as well as prophage and plasmid profiles. It is unclear if the genotypes equally associate with IBK or if one is more likely to be isolated from IBK lesions. We utilized 39 strains of M. bovis that had previously undergone whole genome sequencing and genotype classification to determine the utility of matrix-assisted laser desorption/ionization …

Screening Anti-Pd-L2 Peptides As Antitumor Ligands Using Phage Display, Chien Tran Phuoc

Honors Projects

Cancer still remains one of the top leading causes of death in America. Recently, programmed cell death protein 1 (PD-1) blockades have been demonstrated to be highly effective against various types of cancer. By blocking PD-1 from binding with their ligands (PD-L1 and PD-L2), the “off” signal to the immune system is inhibited, hence reinvigorating the immune cells to kill tumor cells. To date, despite PD-L1 and PD-L2 both interacting with PD-1, research efforts have only been focused on developing anti-PD-L1 inhibitors. Therefore, the work of this honor project has focused on finding anti-PD-L2 peptides by phage display, with the …

Alternative Precautionary Measures Yielding Lower C. Diff Infection Rates In Healthcare Facilities, Matthew Kramer

Symposium of Student Scholars

Background: An international healthcare concern is the persistent spread of Clostridium difficile, a Gram-positive spore forming bacterium that is responsible for the most common hospital-acquired infection, amongst patients.

Objective: A systematic review was performed to summarize evidence that the interventions utilized in healthcare facilities which indicate a patient’s precautionary status are insufficient, outdated, and commonly lead to infection in neighboring patient rooms. Databases such as PubMed, NCBI, Google Scholar, and APHA’s Medical Care were searched, covering the period from 2017-2022. Studies were included if their focus concentrated on C. diff and the precautionary measures taken by employees at healthcare …

Descriptive Dna Barcoding Of Argas (Persicargas) Arboreus And Argas (Persicargas) Persicus Ticks (Ixodida: Argasidae) Infesting Birds In Egypt, Enas H. Ghallab, Ayat Yousery, Mona G. Shaalan

Harold W. Manter Laboratory of Parasitology: Library Materials

Argas ticks are primary parasites of birds with veterinary importance. Nevertheless, these ticks have received little attention regarding molecular identification studies. DNA barcoding is a powerful technique for identifying tick species besides traditional morphological identification. The present work is a first effort to divulge DNA sequences of Argas (Persicargas) arboreus from Egypt and worldwide. We used cytochrome c oxidase subunit I (COI) from A. arboreus infesting herons, and from the fowl tick Argas (Persicargas) persicus. Our results pointed out another success for the Folmer primers that are widely used in DNA barcoding, permitting the discrimination …

Spinal Metastases And The Evolving Role Of Molecular Targeted Therapy, Chemotherapy, And Immunotherapy, Elena I Fomchenko, James C Bayley, Christopher Alvarez-Breckenridge, Laurence D Rhines, Claudio E Tatsui

Faculty, Staff and Student Publications

Metastatic involvement of the spine is a common complication of systemic cancer progression. Surgery and external beam radiotherapy are palliative treatment modalities aiming to preserve neurological function, control pain and maintain functional status. More recently, with development of image guidance and stereotactic delivery of high doses of conformal radiation, local tumor control has improved; however recurrent or radiation refractory disease remains a significant clinical problem with limited treatment options. This manuscript represents a narrative overview of novel targeted molecular therapies, chemotherapies, and immunotherapy treatments for patients with breast, lung, melanoma, renal cell, prostate, and thyroid cancers, which resulted in improved …

Doxorubicin-Induced Cardiotoxicity Is Mediated By Neutrophils Through Release Of Neutrophil Elastase, Anchit Bhagat

Dissertations and Theses (Open Access)

Doxorubicin (Dox) is one of the most effective chemotherapy agents that is used for the treatment of childhood cancer. Unfortunately Dox treatment can cause damage to the heart. Indeed, childhood cancer survivors are at a higher risk of developing a cardiovascular disease at an earlier age. The mechanisms by which Dox causes acute and late cardiotoxicity are not completely understood. One understudied area in Dox-induced cardiotoxicity is the contribution of inflammation and innate immune cells, in particular neutrophils. Recognizing that neutrophils have been implicated in a number of heart diseases, we evaluated the role of neutrophils in Dox-induced cardiotoxicity. Here, …

Understanding And Targeting The Immunosuppressive Tumor Microenvironment, Li Cai, Li Cai

Dissertations and Theses (Open Access)

Immune checkpoint inhibitors (ICIs), such as anti-PD1/PD-L1 and anti-CTLA-4, have shown impressive antitumor efficacy by improving the activity of T cells. While these inhibitors work in many patients with various cancer types, they have minimal or no effect in many more patients. Mounting evidence indicates that, besides current known immune checkpoints, other immunosuppressive components in the tumor microenvironment (TME) need to be targeted to elicit the full immune responses.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of immunosuppressive myeloid cells that are involved in cancer progression and therapeutic resistance. In this work, we demonstrated the essential role of MDSCs …

Optimization Of Clostridium Septicum Antigen Production And Evaluation Of Vaccine Administration Parameters For A Candidate Bacterin-Toxoid To Prevent Dermatitis In Commercial Turkeys, Aaron Forga

Graduate Theses and Dissertations

The objective of this thesis was to optimize the hemolytic activity of two isolates of Clostridium septicum to evaluate if hemolytic titer of C. septicum antigen at time of formalin inactivation corresponded to increased serum antibody titer to the C. septicum alpha-toxin of turkeys immunized with an experimental formalin inactivated bacterin-toxoid vaccine. Chapter 1 provides a brief overview of the thesis. Chapter 2 consists of a literature review focused on clostridial dermatitis, specifically C. septicum-associated dermatitis (cellulitis) that affects commercial turkeys. Chapter 3 outlines our attempts to optimize an experimental autogenous bacterin-toxoid vaccine as a potential strategy to mitigate clostridial …