Immunopathology Commons^™

Identification And Preclinical Assessment Of Novel Therapeutic Modalities In Environmental Exposure-Induced Lung Disease, Aaron D. Schwab

Theses & Dissertations

Environmental lung diseases are preventable respiratory conditions either caused or made worse by inhaled environmental exposures. Contemporarily, environmental lung diseases are most associated with workplace exposures given specific occupational processes aerosolize inflammatory agents that can be inhaled at high concentrations. Although a considerable amount is known regarding immunoglobulin (Ig)E-mediated responses to environmental exposures, little is known about non-IgE mediated respiratory conditions resulting from lipopolysaccharide (LPS)-enriched organic dust exposure(s). Chronic respiratory diseases such as asthma, hypersensitivity pneumonitis, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis have all been identified as environmental lung diseases caused or exacerbated by such environmental dusts. Therapeutic …

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 …

Psychological Trauma Alters T-Lymphocyte Inflammation And Redox Through Sympathetic Mechanisms, Safwan K. Elkhatib

Theses & Dissertations

Posttraumatic stress disorder (PTSD) is a devastating psychiatric disorder characterized by distinctive symptom clusters, including intrusive memories (i.e., flashbacks), avoidance of related stimuli, affective changes, and hyperarousal. Strikingly, patients with PTSD face a significantly increased risk for a number of inflammation-driven pathologies, ranging from cardiovascular to autoimmune disease. Yet, the exact etiology of this increased risk remains unknown. The immune system is known to be strongly influenced by the sympathetic nervous system, and sympathetic overactivity is a hallmark of PTSD. Lymphoid organs, such as the spleen, are richly innervated by sympathetic nerve fibers which terminate near adaptive immune …

The Role Of Calprotectin In T-Lymphocyte Driven Inflammation In A Mouse Model Of Psychological Trauma, Cassandra Moshfegh

Theses & Dissertations

Post-traumatic stress disorder (PTSD) is a debilitating psychological disorder that affects nearly 45 million Americans. This mental disorder is characterized by behavioral symptoms such as learned helplessness, hyperarousal, withdrawal, and flashbacks. The deleterious effects of PTSD are far-reaching and go beyond behavioral dysfunction, as these individuals are at a three-fold higher risk of comorbid inflammatory diseases. Autonomic, metabolic, and cardiovascular diseases plague these individuals later in their lifetime, however, the mechanistic link connecting psychological trauma to this systemic peripheral immunological dysfunction remains elusive. T-lymphocyte-induced inflammation plays a significant role in all these disease pathologies. Previous work from our laboratory demonstrated …

Immunological Factors Associated With Siv/ Shiv Persistence In Diverse Tissue Niches, Omalla A. Olwenyi

Theses & Dissertations

The significant challenge towards a successful HIV cure lies in eradicating persistent viral reservoirs across diverse tissue niches. As a result, HIV-infected individuals have to resort to lifelong antiretroviral therapy. Recent news of supposed HIV eradication in a second patient has further re-invigorated the fields of HIV cure. However, a few barriers remain, such as the lack of currently available assays to accurately quantify viral reservoirs, limited information on cellular factors associated with persistence, and varied dynamics of the viral reservoir in various body compartments. Lastly, HIV-infected individuals live different lifestyles stemming from comorbid substance abuse including consumption of morphine, …

Flavonoid And Cannabidiol Neural Glyoxalase Pathway Enhancement Against Aging And Alzheimer’S Disease, Joel R. Frandsen

Theses & Dissertations

Alzheimer’s Disease is a neurodegenerative condition featuring neural cell death and a decline in cognitive capacity caused by elevated inflammation and production of reactive oxygen species. The glyoxalase pathway is an endogenous antioxidant system that neutralizes reactive methylglyoxal through sequential reactions. Dysfunction of the glyoxalase pathway contributes to oxidative stress and the accumulation of inflammatory metabolic byproducts. Plant-produced compounds with antioxidant activity can enhance endogenous antioxidant pathways and protect cells from elevated ROS production. We hypothesize that flavonoids and limited Cannabis Sativa-produced cannabidiol can enhance glyoxalase pathway function through regulation of antioxidant and pro-apoptotic signaling pathways to prevent methylglyoxal-mediated …

Il-17-Cxcr2 Axis Promotes Breast Cancer Metastasis And Therapy Resistance, Lingyun Wu

Theses & Dissertations

Cancer-related fatalities rank as the second leading cause of death in all ages and both genders in the United States. Moreover, breast cancer-related mortality rank as the second leading cause of death in females in the United States in 2019. The main concerns regarding breast cancer management include chemotherapy resistance and metastasis. Thus, the advanced understanding of cancer progression is required to develop improved therapeutic methods for breast cancer patients.

Recent studies demonstrate that neutrophils, as the most abundant leukocytes, play an essential role in breast progression. However, the mechanisms regarding neutrophils recruitment to the tumor sites, and the precise …

The Cxcr2-Dependent Role Of Cancer-Associated Fibroblasts In Pancreatic Ductal Adenocarcinoma, Mohammad Awaji

Theses & Dissertations

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer, the fourth leading cause of cancer-related deaths in the USA with over 40,000 deaths per year. Unlike other major cancer types, the progress in dealing with PDAC is plodding, attributed mainly to the asymptomatic nature of the disease, the late diagnosis and the ineffectiveness of current therapies. A better understanding of the biology of the disease could permit the discovery of novel diagnostic and therapeutic tools. With that in mind, we present this dissertation that investigates the tumor-stromal interaction underlined by genetic alterations and inflammation. PDAC develop as …

Elucidation Of The Functions Of Neuropilin 2 In Osteoclasts In Promoting Prostate Cancer Bone Metastasis., Navatha S. Polavaram

Theses & Dissertations

Bone metastasis is one of the major clinical concerns that causes skeletal related malignancies and increased mortality. Bone is one of the preferred sites for metastatic prostate cancer. The metastatic prostate cancer cells interact with bone cells (osteoblasts and osteoclasts) resulting in an imbalance in the bone homeostasis leading to increased activation of osteoblasts over osteoclasts. Our preliminary data indicated a non-tyrosine kinase receptor Neuropilin 2 (NRP2) is expressed in osteoclasts induced by metastatic prostate cancer cells and acts as a negative regulator of osteoclast differentiation and function. We hypothesize that prostate cancer -induced NRP2 expression in osteoclasts is necessary …

Defining The Role Of Neuropilin-2 In Macrophages: Implications In Tumor Associated Macrophages In Pancreatic Cancer, Sohini Roy

Theses & Dissertations

Macrophages are extremely heterogeneous and highly plastic hematopoietic cells that reside in all tissues and act as a bridge between the innate and adaptive arms of the immune responses. Besides, they undertake a wide array of housekeeping functions like, clearance of cellular debris that arise due to regular turnover in tissues, iron homeostasis, immune surveillance as well as tissue repair processes post inflammation. They are also causally associated with several clinical conditions, including cancer where the infiltration of macrophages contribute to disease progression, metastasis and therapy resistance, and thereby poor clinical outcome.

Neuropilins (NRPs) are non-tyrosine kinase cell surface glycoproteins …

Effects Of Gm-Csf On Dendritic Cells And Regulatory T Cells In Parkinson’S Disease Patients And Models Of Parkinson’S Disease, Charles Schutt

Theses & Dissertations

Parkinson’s disease (PD) is the most common neurodegenerative movement disorder. Pathologically, loss of nigrostriatal neurons and dopamine released by these neurons are responsible for PD motor symptoms. During PD, activation of resident microglia and infiltrating lymphocytes leads to progressive neuroinflammation and reduction in the number and function of regulatory immune cells. Neuroinflammation contributes to progressive neurodegeneration and declining motor function. Reducing neuroinflammation is the target for novel PD therapeutics. Our goal is to increase the number and function of regulatory T cells (Tregs) in PD patients to decrease neuroinflammation and reduce PD symptoms. One potential therapy is granulocyte-macrophage colony stimulating …

Defining The Role Of Interferon Regulatory Factor 4 In Chronic Lymphocytic Leukemia., Vipul Shukla

Theses & Dissertations

Chronic Lymphocytic Leukemia (CLL) represents the most common adult leukemia in the Western hemisphere. Despite considerable progress in our current understanding of CLL, this disease remains incurable and the molecular events underlying the complex pathogenesis of CLL are not fully elucidated. Interferon Regulatory Factor 4 (IRF4) belongs to the IRF superfamily of transcription factors that has been shown to play critical roles at multiple stages of B cell development. Interestingly, a Genome Wide Association Study identified Single Nucleotide Polymorphism (SNP) mediated IRF4 down regulation, as a major predisposing genetic event during the development of CLL. However, whether low levels of …