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Articles 1 - 14 of 14
Full-Text Articles in Life Sciences
T Cell Immunity In Pancreatic Cancer Is Undermined By Dendritic Cell Dysfunction, Samarth Hegde
T Cell Immunity In Pancreatic Cancer Is Undermined By Dendritic Cell Dysfunction, Samarth Hegde
Arts & Sciences Electronic Theses and Dissertations
Pancreatic cancer carries a dismal prognosis, and desperately needs viable therapeutic interventions beyond chemo-radiation. T cell-dependent immunotherapies have shown great promise in several tumor types, but have not been effective for the vast majority of pancreatic cancer patients. This is, in part, due to our limited understanding of how antigenicity of pancreatic lesions is recognized, and how adaptive immunity is overcome in this disease. We sought to study tumor-immune interactions and identify mechanisms for this immune-failure using several spontaneous and unperturbed mouse models of pancreatic adenocarcinoma. We found that early pancreatic lesions fail to elicit tumor-limiting CD4+ TH1 and CD8+ …
The Transcription Factor Bhlhe40 Regulates Tissue-Resident Macrophages And Type 2 Immunity, Nicholas N. Jarjour
The Transcription Factor Bhlhe40 Regulates Tissue-Resident Macrophages And Type 2 Immunity, Nicholas N. Jarjour
Arts & Sciences Electronic Theses and Dissertations
Transcriptional control of gene expression is essential for life, tailoring protein production to development and environment to maintain organismal homeostasis. A limited set of proteins termed transcription factors are critical to this process. As our understanding of these central regulators has improved, new aspects of cell and organismal biology have been revealed. Herein, we demonstrate the importance of the transcription factor Bhlhe40 to tissue-resident macrophages, T helper type 2 cells, and type 2 immune responses, revealing novel transcriptional control of macrophages and unexpected cytokine regulation of helminth infection. We find that Bhlhe40 is cell-intrinsically required for normal proliferation of large …
Generation And Utilization Of Diverse Memory B Cells After Flavivirus Challenges, Rachel Wong
Generation And Utilization Of Diverse Memory B Cells After Flavivirus Challenges, Rachel Wong
Arts & Sciences Electronic Theses and Dissertations
Over the course of an effective immune response to an infection, two distinct B cell populations are generated to provide protection against reinfection, long-lived plasma cells (LLPCs) and memory B cells (MBCs). LLPCs and MBCs originate from germinal center (GC) B cells that have undergone B cell receptor (BCR) affinity maturation through iterative rounds of somatic hypermutation, proliferation, and selection. Thus, LLPCs and MBCs can bind to their antigen with higher affinity than their naïve B cell precursors. LLPCs constitutively secrete antibodies and can provide sterilizing immunity that pre-exists subsequent infections. MBCs, on the other hand, are quiescent and provide …
Investigating Biological Mechanisms Of Radiation Resistance In Advanced Stage Cervical Cancer, Fiona Ruiz
Investigating Biological Mechanisms Of Radiation Resistance In Advanced Stage Cervical Cancer, Fiona Ruiz
Arts & Sciences Electronic Theses and Dissertations
The current standard of care treatment for locally advanced cervical cancer is curative intent pelvic radiation with concurrently administered platinum chemotherapy (CRT). This treatment strategy is effective for many patients, but 33-50% of patients treated with CRT develop disease recurrence. Metastatic and recurrent cervical cancer is an incurable condition, and many of the currently available treatments are associated with significant morbidity and mortality. Identifying these patients upfront is a challenge that clinicians face when developing treatment strategies. Previous studies used to catalog the genomic and transcriptomic landscape of cervical cancer lacked high quality corresponding clinical follow up data for patients, …
Mesothelium-Derived Factors Shape Tissue Resident Macrophage, Chin-Wen Lai
Mesothelium-Derived Factors Shape Tissue Resident Macrophage, Chin-Wen Lai
Arts & Sciences Electronic Theses and Dissertations
The studies outlined in this thesis provide several new insights into Msln-related pathways necessary for peritoneal immune responses and mucosal repair. We found that Msln and its binding partner mucin 16 from mesothelium influenced peritoneal and pleural macrophage differentiation. We found that Msln was required for proper tissue repair after colonic biopsy injury and was required for maximal polyp growth in APCMin/+ mice. Overall, this work describes mesothelial and epithelial-derived factors that are important for tissue resident macrophage differentiation and wound repair after colonic mucosal injury. Understanding the complex interactions between stromal cells and immune cells will lead to better …
Understanding The Transcriptional Mechanisms Underlying Dendritic Cell Development, Prachi Bagadia
Understanding The Transcriptional Mechanisms Underlying Dendritic Cell Development, Prachi Bagadia
Arts & Sciences Electronic Theses and Dissertations
Dendritic cells (DCs) comprise an important immune lineage that plays a critical role in initiating and sustaining the proper immune response. They can be divided into two distinct branches, classical/conventional DCs (cDCs) or plasmacytoid DCs (pDCs). cDCs can further be classified as cDC1 or cDC2. Each DC subset exerts unique functions in vivo and are necessary for a complete immune response. The precise transcriptional programs underlying DC specification and commitment remain unclear. cDC1, cDC2, and pDC all arise from the common DC progenitor (CDP) in the bone marrow. How the CDP gives rise to all three DC subsets in an …
Secretory Iga Enhances Gut B Cells Priming And Systemic Igg Responses Towards Commensals, You Zhou
Secretory Iga Enhances Gut B Cells Priming And Systemic Igg Responses Towards Commensals, You Zhou
Arts & Sciences Electronic Theses and Dissertations
IgA is the primary antibody response at mucosal surfaces and is reported to inhibit adaptive immune responses against gut bacteria. Here, we utilize an in vitro system to expand and screen IgA memory B cells for their ability to recognize gut bacteria in the context of secretory IgA (sIgA) deficiency in polymeric Ig receptor (Pigr–/–) mice. Contrary to the prevailing hypothesis that IgA provides an immune exclusionary function, we found that mice lacking sIgA showed decreased anti-bacterial IgA specificities as assessed using flow cytometry. IgA B cell responses against certain taxa such as those of order Bacteriodales showed greater dependence …
Quantitatively Studying Tissue Damage In Multiple Sclerosis Using Gradient Recalled Echo Mri Sequences, Biao Xiang
Quantitatively Studying Tissue Damage In Multiple Sclerosis Using Gradient Recalled Echo Mri Sequences, Biao Xiang
Arts & Sciences Electronic Theses and Dissertations
Multiple Sclerosis (MS) is an unpredictable, often disabling disease of the central nervous system (CNS) that disrupts the flow of information within the brain, and between the brain the body. MS is the most common progressive neurologic disease of young adults, affecting approximately 2.3 million people worldwide. It is estimated that more than 700,000 individuals are affected by MS in United States. While MS has been studied for decades, the cause of it is still not definite and a fully effective treatment for MS is not yet available. Magnetic resonance imaging (MRI) has been used extensively in MS diagnosis and …
Exploring Infant Leukemia Through Exome Sequencing And An In Vitro Model Of Hematopoietic Development, Mark Cannon Valentine
Exploring Infant Leukemia Through Exome Sequencing And An In Vitro Model Of Hematopoietic Development, Mark Cannon Valentine
Arts & Sciences Electronic Theses and Dissertations
Cancer is a heterogeneous disease with myriad causes and outcomes. Many of the cancers that occur in adult populations have become increasingly well characterized with the advent of affordable high-throughput sequencing. These studies have revealed that cancer is largely a disease of somatic mutation in the adult population. In strong contrast to this, childhood cancers have an exceedingly low rate of somatic mutation. At the extreme end of this spectrum is Infant Leukemia (IL). Sequencing of IL has revealed that these tumors frequently have one or fewer somatic SNP. In the absence of a somatic explanation for IL, many other …
Development Of Enteric Neurons And Muscularis Macrophages, Marina Avetisyan
Development Of Enteric Neurons And Muscularis Macrophages, Marina Avetisyan
Arts & Sciences Electronic Theses and Dissertations
The enteric nervous system (ENS) is a complex interconnected network of neurons and glia in the bowel wall that regulates intestinal motility, blood flow, and epithelial function. The ENS also controls aspects of inflammatory signaling within the bowel. To perform these tasks, there are at least 20 types of enteric neuron and four types of enteric glia. Although much is known about early events in ENS development, signals governing the development of specific neuronal subtypes and communication with neighboring cell types within the bowel remain poorly understood. One fundamental hypothesis is that diverse trophic factors support distinct neuronal populations in …
The Role Of Tumor Stromal Discoidin Domain Receptor 2 (Ddr2) In Breast Cancer Metastasis., Samantha Van Hove Bayer
The Role Of Tumor Stromal Discoidin Domain Receptor 2 (Ddr2) In Breast Cancer Metastasis., Samantha Van Hove Bayer
Arts & Sciences Electronic Theses and Dissertations
Characteristics of breast tumor stroma, including altered collagen architecture and increased stiffness, are known to contribute to tumor invasion and metastasis. However, the cellular and molecular mechanisms by which these changes occur are not fully understood. To address this question, we used a mouse genetic model to delete Discoidin Domain Receptor 2 (DDR2) from mouse tumor stromal cells and interrogated breast cancer associated fibroblasts (CAFs) to determine the molecular events downstream of DDR2 action that may lead to changes in the tumor extracellular matrix (ECM). Our work revealed that the action of DDR2 in breast stromal cells is required for …
Characterizing The Humoral Response To Flavivirus Infection, Estefania Fernandez
Characterizing The Humoral Response To Flavivirus Infection, Estefania Fernandez
Arts & Sciences Electronic Theses and Dissertations
Flaviviruses are positive (+) sense, single-stranded RNA viruses of the Flaviviridae family that are transmitted by mosquitoes. For our studies, we focused on Zika virus (ZIKV) and Japanese encephalitis virus (JEV). Most human infections with ZIKV historically resulted in a mild self-limiting febrile illness. However, since 2013, a worldwide spread and increase in ZIKV infections has been observed. Notably, ZIKV has been associated with autoimmune ascending paralysis (Guillain-Barré Syndrome) and ophthalmologic effects in adults and intrauterine growth restriction and microcephaly in developing fetuses. Current vaccine efforts utilize technologies implemented for related flaviviruses (yellow fever virus (YFV), Dengue virus (DENV), and …
Dissemination Of The Apicomplexan Parasite, Toxoplasma Gondii, Lisa L. Drewry
Dissemination Of The Apicomplexan Parasite, Toxoplasma Gondii, Lisa L. Drewry
Arts & Sciences Electronic Theses and Dissertations
The parasitic protist Toxoplasma gondii is a common pathogen of rodents and felines that also infects humans. The most severe clinical manifestations of toxoplasmosis in humans derive from the systemic dissemination of T. gondii, during which the parasite penetrates biological barriers and accesses protected host compartments such as the central nervous system. T. gondii dissemination is enabled by the intrinsic gliding motility of extracellular parasites, which allows for travel to new host cells and tissues, and also powers the invasion of diverse host cells including migratory leukocytes. Dissemination is further advanced when migrating infected leukocytes shuttle intracellular parasites to new …
Activation Of Toll-Like Receptor 3 Translates To Long-Term Post-Viral Lung Disease, Xinyu Wang
Activation Of Toll-Like Receptor 3 Translates To Long-Term Post-Viral Lung Disease, Xinyu Wang
Arts & Sciences Electronic Theses and Dissertations
Chronic obstructive lung disease (COPD) causes substantial human and economic costs both in the US and worldwide. To identify the molecular mechanisms to allow for targeted therapies for COPD, we developed a high-fidelity mouse model of chronic lung inflammation using the natural rodent pathogen Sendai virus (SeV). While nucleic acid-sensing pattern recognition receptors are important for innate immune responses to viral pathogens, there have been few studies investigating their role in the context of chronic disease. Here we show that Toll-like receptor 3 (Tlr3) signaling is required for the development of chronic lung disease in a postviral mouse model. Activation …