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Articles 1 - 7 of 7
Full-Text Articles in Medicine and Health Sciences
Uncovering A Myc-Driven Tumor-Suppressive Program In Proliferating Lymphocytes, Elena Tonc
Uncovering A Myc-Driven Tumor-Suppressive Program In Proliferating Lymphocytes, Elena Tonc
Arts & Sciences Electronic Theses and Dissertations
Rapid cell proliferation is a hallmark feature of adaptive immune cells lymphocytes. It is essential for the establishment of diverse antigen receptor repertoires and amplification of antigen-specific immune responses. While such proliferation is beneficial for host protection from infections and cancers, it inevitably elevates the risk of oncogenic transformation. In developing and germinal center B lymphocytes, the risk is further increased by endogenous, genomic insults due to antigen receptor rearrangements and somatic mutations, with which expression of the proto-oncogene c-MYC is closely associated. Nonetheless, frequencies of cancers originated from B lymphocytes are relatively low, suggesting that they are protected from …
Mechanisms Of Cross-Presentation By Cdc1s, Derek James Theisen
Mechanisms Of Cross-Presentation By Cdc1s, Derek James Theisen
Arts & Sciences Electronic Theses and Dissertations
Classical dendritic cells (cDCs) are specialized antigen presenting cells that can be divided into distinct subsets based on the types of pathogens they respond to and the type of immune response they generate. The cDC1 subset is specialized in priming CD8 T cell responses through the process of cross-presentation. During cross-presentation, exogenous protein antigens are taken up by cDC1 and presented on MHCI molecules, allowing for the priming of CD8 T cells during conditions when DCs themselves are not directly infected. The ability to cross-present in vivo is unique to cDC1, and is essential for anti-viral responses and rejection of …
Increasing Ph In Cancer: Enabling A New Therapeutic Paradigm Using Novel Carbonate Nanoparticles, Avik Som
Increasing Ph In Cancer: Enabling A New Therapeutic Paradigm Using Novel Carbonate Nanoparticles, Avik Som
McKelvey School of Engineering Theses & Dissertations
Enormous progress has been made to treat cancer, and yet the mortality rate of cancer remains unacceptably high. High clinical resistance to molecularly targeted therapeutics has pushed interest again towards inhibiting universal biochemical hallmarks of cancer. Recent evidence suggests that malignant tumors acidify the local extracellular environment to activate proteases for degrading the tumor matrix, which facilitates metastasis, and explains why more aggressive tumors are more acidic. Current therapies have only focused on using the low pH for enhancing drug release in tumors, thereby still relying on the traditional paradigm of intracellular inhibition of pathways, a method that continues to …
Tumors Interrupt Irf8-Mediated Dendritic Cell Development To Overcome Immune Surveillance, Melissa Ann Meyer
Tumors Interrupt Irf8-Mediated Dendritic Cell Development To Overcome Immune Surveillance, Melissa Ann Meyer
Arts & Sciences Electronic Theses and Dissertations
Tumors employ multiple mechanisms to evade immune surveillance. One mechanism is tumor-induced myelopoiesis, which expands immune suppressive granulocytes and monocytes to create a protective tumor niche shielding even antigenic tumors. As myeloid cells and immune-stimulatory conventional dendritic cells (cDCs) are derived from the same progenitors, it is logical that tumor-induced myelopoiesis might also impact cDC development. The cDC subset cDC1 is marked by CD141 in humans and CD103 or CD8α in mice. cDC1s act by cross presenting antigen and activating CD8+ T cells. Given these functions, CD103+ cDC1s can support anti-tumor CD8+ T cell responses. However, CD103+ cDC1 numbers are …
Mitochondrial Dynamics Controls T Cell Fate Through Metabolic Programming, Michael Buck
Mitochondrial Dynamics Controls T Cell Fate Through Metabolic Programming, Michael Buck
Arts & Sciences Electronic Theses and Dissertations
Activated effector T (TE) cells augment anabolic pathways of metabolism, such as aerobic glycolysis, while memory T (TM) cells engage catabolic pathways, like fatty acid oxidation (FAO). However, signals that drive these differences remain unclear. Mitochondria are metabolic organelles that actively transform their ultrastructure. Therefore, we questioned whether mitochondrial dynamics controls T cell metabolism. We show that TE cells have punctate mitochondria, while TM cells maintain fused networks. The fusion protein Opa1 is required for TM, but not TE cells after infection, and enforcing fusion in TE cells imposes TM cell characteristics and enhances antitumor function. Our data suggest that, …
Dox Inducible Idh2 R140q Expression In Stem Cells Results In Cell Death, Opposite Of Cancerous Overgrowth, Reuben Hogan
Dox Inducible Idh2 R140q Expression In Stem Cells Results In Cell Death, Opposite Of Cancerous Overgrowth, Reuben Hogan
Undergraduate Research Symposium Posters
Mutations in isocitrate dehydrogenase (IDH) 1 or 2 are found in about 23% of acute myeloid leukemia (AML) samples and about 90% of gliomas. Mutations result in neomorphic function of the IDH enzyme that yields the novel molecule 2-hydroxyglutarate (2HG) instead of alpha-ketoglutarate (aKG). 2HG is known to be associated with hypermethylation of DNA and histones, a phenotype seen in AML. Our lab intends to study the mechanism by which hypermethylation is achieved and how this mechanism relates to the onset of cancer. In this experiment, we utilized a line of H9 stem cells which we had developed. These cells …
State Space Analysis Of Dominant Structures In Dynamic Social Systems, Jeremy B. Sato
State Space Analysis Of Dominant Structures In Dynamic Social Systems, Jeremy B. Sato
McKelvey School of Engineering Theses & Dissertations
Many systems involving human relationships are modeled as dynamic systems, as diverse as urban population growth, diffusion of innovations, spread of viruses, and supply chain management. A fundamental assumption is that these systems contain variables which accumulate and deplete over time (people, innovation adoptions, infections, and orders), and whose dynamics are determined by societal rules and human decision making processes. These assumptions allow the system to be formally expressed by ordinary differential equations which are often nonlinear and contain multiple state variables and feedback loops. Analytical methods have been developed to identify the dominant feedback loops which primarily influence the …