Immunology and Infectious Disease Commons^™

Dynamical Systems Modeling To Determine The Role Of Crosstalk In Shaping Stat Signaling Profiles, Laura F. Strube, Anamarie Martinez, Neha Cheemalavagu, Karsen Shoger, James Faeder, Rachel Gottschalk

Biology and Medicine Through Mathematics Conference

No abstract provided.

Impact Of The Dose And The Number Of Transmitted/Founder Viruses On Siv Dynamics, Sunil Maity, Vitaly V. Ganusov

Biology and Medicine Through Mathematics Conference

No abstract provided.

Mctr3 Mitigates Cigarette Smoke-Induced Pulmonary Inflammation And Damage, Yu Par Aung Myo

Theses and Dissertations

Smoking is deleterious to our lungs and can precipitate in a multitude of diseases, including chronic obstructive pulmonary disease (COPD). COPD is primarily caused by smoking cigarettes and is a major public health issue. Current therapies only treat symptoms without halting or reversing disease progression, thus highlighting a large unmet need to develop new therapies. We address this gap by investigating maresin conjugate in tissue regeneration 3 (MCTR3) which is a newly discovered specialized pro-resoling mediator (SPM) that has the novel property of promoting tissue repair and regeneration in addition to being anti-inflammatory and pro-resolving. For the first time, we …

Dickkopf1(Dkk1): A Novel Endogenous Ligand To Prime Nlrp3 Inflammasome Via Tlr4, Theingi Aung

Theses and Dissertations

Dickkopf1(DKK1) is a quintessential Wnt antagonist and immunomodulator in various inflammatory diseases. The underlying molecular mechanisms of DKK1-mediated immunomodulation remain elusive. Here, we identified TLR4 as a new receptor for DKK1 to activate NFκΒ pathway-mediated gene expression and pyroptosis via NLRP3 inflammasome in human and mouse macrophages.

DKK1 employed TLR4 to initiate NFκB signaling cascade via MyD88. MyD88-TAK1-NFκΒ pathway activation by DKK1 increased HIF1α, NFκB, and NLRP3 protein expression levels, leading to pyroptosis. Unlike LPS, DKK1 did not induce IRAK4 phosphorylation, while the interaction between MyD88 and IRAK4 was maintained for downstream signaling activation. DKK1 did not induce IRF3 phosphorylation …

Exploring The Role Of Host Immune Responses And Bacterial Sensory Pathways In The Development Of Treponema Denticola-Mediated Periodontal Disease, Annie N. Hinson

Theses and Dissertations

Periodontitis is a chronic inflammatory disease driven by dysbiotic microbial communities and maladaptive host responses. Treponema denticola, a spirochete pathobiont, is strongly associated with disease severity. However, the molecular mechanisms underlying its interaction with host tissues and regulation of virulence remain incompletely understood. This work examines both the epithelial immune responses and bacterial transduction systems that shape T. denticola pathogenesis. Transcriptomic analysis of gingival keratinocytes revealed IL-36γ as the most highly induced cytokine following infection with T. denticola. Functional studies demonstrated that IL-36γ induction occurs in a dose- and time-dependent manner through TLR2/6 signaling, requiring the NF-κB, PI3K/Akt, and …

Functional Analysis Of Ligand Binding Domain 2 Of Outer Surface Protein C Of Borreliella Burgdorferi, Gavin Z. Chambers

Theses and Dissertations

Lyme disease, caused by the spirochete Borreliella burgdorferi, is the most common vector-borne infection in North America. A critical determinant of early mammalian infection is outer surface protein C (OspC), a highly variable lipoprotein that is indispensable for spirochete survival but whose precise function remains unresolved. OspC has been proposed to mediate diverse roles, including complement evasion, adhesion, tissue dissemination, and antiphagocytic activity, supporting the view that it is a multifunctional virulence factor. Structural studies have identified two putative ligand-binding domains (LBD1 and LBD2), with LBD2 forming a solvent-exposed crown at the membrane-distal end of the OspC dimer.

To …

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.

Sphingosine Kinase 2 Depletion Dysregulates Hepatic Redox Metabolism And Enhances Inflammation In Early Metabolic Dysfunction-Associated Steatohepatitis (Mash), Kaitlyn Georgene Jackson

Theses and Dissertations

Metabolic dysfunction-associated steatotic liver disease (MASLD) currently affects one in three people worldwide; its prevalence is growing alongside other cardiometabolic disorders. Aberrations to redox and sphingolipid metabolism contribute to MASLD pathologic progression. Sphingosine-1-phosphate (S1P) is an active lipid, meaning that S1P participates in biochemical processes within the cell. S1P is generated by two distinct isoenzymes, sphingosine kinase (SphK)1 and SphK2. The localization of the SphK enzyme dictates S1P function. While cytosolic SphK1-generated S1P is well-characterized, nuclear and mitochondrial SphK2-generated S1P is less known. Moreover, SphK2 depletion effects on cellular redox processes and inflammation are not well-defined.

This study defines the …

The Role Of Hdac6 In Periodontal Inflammation, Hannah S. Lohner

Theses and Dissertations

Periodontal disease is a polymicrobial infection-induced chronic inflammatory disease and results in irreversible tissue damage and bone loss. While bacteria play a large role in the initiation of this disease, excessive and prolonged inflammatory immune responses are fundamental for its progression, making host directed therapy (HDT) a possible and potentially valuable treatment. Histone Deacetylase 6 (HDAC6) is an enzyme that removes acetyl groups from both histone and non-histone proteins, giving it a potential role in regulating inflammation initiated by pathogenic oral bacteria. Previous studies indicated that HDACs act as a bivalent regulator in inflammatory responses; however, the role that HDAC6 …

Appearance Of Multistability And Hydra Effect In A Discrete-Time Epidemic Model With Ricker Growth, Laura F. Strube, Shoshana Elgart, Lauren Childs

Biology and Medicine Through Mathematics Conference

No abstract provided.

Modeling The Immune Response To Immunotherapy And Triple Negative Breast Cancer In Mice, Dayton J. Syme, Angelica Davenport, Yun Lu, Anna G. Sorace, Nicholas G. Cogan

Biology and Medicine Through Mathematics Conference

No abstract provided.

Predicting Dengue Incidence In Central Argentina Using Google Trends Data, Sahil Chindal, Elizabet Estallo, Yanjun Qian, Michael Robert

Biology and Medicine Through Mathematics Conference

No abstract provided.

Proposing An Rna Interference (Rnai)-Based Treatment For Human Immunodeficiency Virus (Hiv) By Analyzing The Post-Transcriptional Gene Targeting Of Sars-Cov-2, Hepatitis C Virus, And A549 Lung Cancer Cells, Arjun Jagdeesh

UROP Posters

Human Immunodeficiency Virus (HIV) is a retrovirus that infects CD4+ T cell lymphocytes in humans, leading to the development of Acquired Immunodeficiency Syndrome (AIDS) if left untreated. While current treatment methods, including antiretroviral combination treatments, effectively limit HIV replication, HIV can evade these treatments due to its high mutation rate. Long-term antiretroviral treatment can also be toxic to patients, meaning patients would benefit from a new mechanism of HIV treatment. RNA interference (RNAi) is an antiviral pathway found in mammals, plants, and insects that involves a small-interfering RNA that is incorporated into a protein complex called the RNA-induced Silencing Complex …

Interactions Between Hiv And Opioids On Antiretroviral Accumulation, The Blood Brain Barrier, And The Inflammatory Response In The Brain., Kara Rademeyer

Theses and Dissertations

The complex mechanisms related to HIV infection, neurodegeneration, and chronic neuroinflammation collectively describe neuroHIV (Hauser et al. 2007; Chang et al. 2014; Smith et al. 2014). Specifically, opioid abuse, poor penetration of antiretroviral (ARV) drugs, chronic inflammation and neuronal injury/degeneration are all implicated in neuroHIV (Fantuzzi et al. 2003; Letendre et al. 2004; Verani et al. 2005; Duncan and Sattentau 2011; Hong and Banks 2015; Simoes and Justino 2015; Olivier et al. 2018; Murphy et al. 2019; Osborne et al. 2020). For the first time, we demonstrate that morphine, fentanyl, and methadone in vivo alter the brain accumulation of ARVs, …

The Hepatic Immunological Pattern Shaped By Dominant-Subdominant Cellular Interactions Creates A Collective Function Beyond The Function Of Each Cellular Constituent To Orchestrate Progression Of Hepatocellular Carcinoma, Nicholas J. Koelsch

Theses and Dissertations

Abundance of data on the role of inflammatory immune responses in the progression or inhibition of hepatocellular carcinoma (HCC) has failed to offer a curative immunotherapy for HCC. This is largely because of taking reductionist approaches and missing the collective function of the hepatic immune system by focusing on specific immune cell types. To this end, we propose that focusing on the dominant-subdominant patterns of the immune cells would allow understanding of the mechanism by which a collective immune function emerges. To identify the collective immune function through a systems immunology perspective, we performed high-throughput analysis of snRNAseq data collected …

The Impact Of Hiv-1 Tat And Morphine On Spatial Distribution Of Drugs In The Brain., Austin M. Jones

Theses and Dissertations

Despite combination antiretroviral therapy effectively suppressing HIV within the periphery, the central nervous system (CNS) remains affected by the virus. Approximately half of people living with HIV will experience HIV-associated neurocognitive disorders (HAND) or neuroHIV. Concurrent opioid use exacerbates neuroHIV by promoting neuroinflammation, viral replication, and potentially altering the antiretroviral concentrations within the brain.

Using a transgenic mouse that expresses the HIV-1 Tat protein, we examined the effects of Tat and morphine on antiretroviral accumulation and distribution and the effects of Tat on morphine accumulation within the brain using infrared matrix-assisted laser desorption electrospray ionization with mass spectrometry imaging (IR-MALDESI-MSI). …

Mathematical Model Of Immune-Inflammatory Response In Covid-19 Patients, Quiyana M. Murphy

Biology and Medicine Through Mathematics Conference

No abstract provided.

Evaluating The Practical Identifiability Of A Malaria Model To Assess Conversion To Transmissible Stages, Anthony Raymond Krueger, Damie Pak, Megan Greischar, Lauren Childs

Biology and Medicine Through Mathematics Conference

No abstract provided.

Introduction Of Plasmid Dna Into Sneathia Vaginalis; The First Step To Genetic Manipulation, Rea Mansukhani, Cathyrn O'Brien, Zion Mccoy, Kimberly K. Jefferson

UROP Posters

Many bacterial pathogens are capable of secreting one or more toxins, all of which can be categorized based on their function, target, or mechanism of action. Pore-forming toxins, for instance, are characterized based on their ability to perforate the host membrane. This may result in the delivery of bacterial substances into the host cell, release of compounds from the host cell, and/or death of the host cell. Research from our lab has demonstrated that Sneathia vaginalis, a gram-negative anaerobic bacterial species that is associated with bacterial vaginosis and preterm birth, produces a pore-forming toxin referred to as cytopathogenic toxin …

Determining Effective Treatment Regimens For Breast Cancer Using Combined Immunotherapy And Chemotherapy In Vivo, Akhila R. Kunuthuru, Laura Graham, Harry D. Bear Md, Phd

UROP Posters

Breast cancer has the highest incidence rate of all cancers globally in women, and those of African descent, especially West African females, face higher rates of triple-negative breast cancer (TNBC), a more aggressive form of breast cancer. Immunotherapy for breast cancer is a relatively new treatment option, and research is ongoing to identify the best combination treatments for increasing survival of those diagnosed with TNBC. Eganelisib (IPI-549: a PI3K-gamma inhibitor that works to shift M2 macrophages to M1 to augment T cell function) with other combinatory treatments has shown promising results in reducing tumor growth and increasing survival in mice. …

Regulation Of Osseous Healing By Macrophage-Derived Wnt Ligands, Jefferson Overlin Abaricia

Theses and Dissertations

Osseous healing is regulated by various classes of cells and signaling mechanisms. Of these, Wnt signaling has long been known to be critically important in directing the differentiation of mesenchymal stem cells (MSCs) into osteoblasts during bone healing. However, the source of these Wnt ligands is not known. Recently, a body of literature has arisen finding both beneficial and detrimental effects of macrophage-derived Wnt ligands on the regeneration of other tissues (liver, kidney, heart, and intestine), often by regulating inflammatory activation and stem cell behavior. As macrophages have been well-characterized as orchestrators of healing, their use of Wnt signaling to …

Il-36g Cytokine Induction In Oral Epithelial Cells Triggered By Treponema Denticola And Their Role In Chronic Periodontitis, Christopher Blake

Theses and Dissertations

Periodontal disease is a polymicrobial disease affecting 10-15% of the population. Periodontal disease affects the quality of life by reducing mastication and potentially causing tooth loss. Periodontal disease is also linked to more severe, systemic diseases such as cardiovascular disease and rheumatoid arthritis. Development of the diseased state occurs when the plaque biofilm shifts from healthy to dysbiotic. The shift to a dysbiotic biome brings with it a shift in bacterial presence, specifically an increase in gram-negative bacteria, such as T. denticola. T. denticola is a gram-negative, anaerobic spirochete whose relationship with oral epithelial cells is poorly understood. Preliminary data …

A Novel Immunostimulatory Platform For Amplifying The Abscopal Response Rates Of Radiation Therapy, Patrick A. Paez

Theses and Dissertations

Radiation therapy (RT) is one of the primary treatment modalities for head and neck squamous cell carcinoma (HNSCC). At the time of diagnosis two-thirds of HNSCC patients have local-advanced disease and 50-60% of these patients will experience a local-regional or metastatic relapse within three years. Improving the immunogenic response of RT may help address this clinical problem. However, current RT regimens have failed to reliably generate robust antitumor immunity as evidenced by the rarity of clinical abscopal responses. Recently we engineered a chimeric fusion molecule called Flagrp170, a novel immunostimulatory agent highly capable of promoting antigen presentation and T-cell activation. …

Impact Of Physical Activity And Cardiorespiratory Fitness On Vascular Homeostasis In Premenopausal Women Consuming A Westernized High-Fat Meal, Lauren N. Pedersen

Theses and Dissertations

A large percentage of adults in industrialized nations consume a Westernized dietary pattern, which contributes to fasting dyslipidemia and increased risk for atherosclerotic cardiovascular disease. Evidence suggests that a single Westernized meal containing high saturated fat may induce alterations in blood lipids as well as disturb multiple factors regulating peripheral vascular homeostasis, including innate immune cell function, oxidative stress, and vascular function. Conversely, participation in acute and chronic exercise may beneficially impact an individual’s postprandial response. Therefore, this dissertation contains three manuscripts seeking to describe how acute exercise, cardiorespiratory fitness, and physical activity level impact the lipemic and vascular homeostatic …

Pushing The Limits: Increasing The Speed And Specificity Of Sars-Cov-2 Testing, Grayson Way

Theses and Dissertations

The prevalence and spread of the current COVID-19 pandemic have highlighted the importance of continual improvements upon current microbiological testing methods. Rapid and accurate testing can help mitigate spread by improving on the time to quarantine and quarantine duration required. As of the writing of this thesis, COVID-19 has been responsible for more than 500,000 deaths in the United States of America, and greater than 2 million deaths globally. The work done in this thesis has shown improvements in the current SARS-CoV-2 testing methodology by reducing the time it takes for patient testing while maintaining accuracy and the sensitivity required …

Modeling Vaccination Strategies To Control White-Nose Syndrome In Little Brown Bat Colonies, Eva Cornwell, David Elzinga, Shelby R. Stowe, Alex Capaldi

Biology and Medicine Through Mathematics Conference

No abstract provided.

Mathematical Modeling Of The Car T-Cell Therapy, Emek Kose, Elizabeth Zollinger, Samantha Elliott

Biology and Medicine Through Mathematics Conference

No abstract provided.

In Silico Mouse Model Of Infection And Immunity, Daniel Jonas, Michael Kirby, Alan R. Schenkel

Biology and Medicine Through Mathematics Conference

No abstract provided.