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Yale University

2006

Health Sciences

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B Cells At The Interface Of Innate And Adaptive Immunity In Systemic Lupus Erythematosus: Requirements For The Activation Of Autoreactive B Cells In Autoimmune Disease, Sean Ryan Christensen May 2006

B Cells At The Interface Of Innate And Adaptive Immunity In Systemic Lupus Erythematosus: Requirements For The Activation Of Autoreactive B Cells In Autoimmune Disease, Sean Ryan Christensen

Yale Medicine Thesis Digital Library

Systemic autoimmune disease is characterized by loss of immunologic tolerance to a restricted set of self-nuclear antigens. These macromolecular complexes can be grouped into two categories: DNA-containing autoantigens such as chromatin, and RNA containing autoantigens such as Smith antigen (Sm) and related ribonucleoprotein complexes. Elucidating the mechanism for selective targeting of these molecules in systemic lupus erythematosus (SLE) may provide clues to the etiology of disease. We hypothesized that Toll-like receptors (TLRs), germline-encoded pattern-recognition receptors of the innate immune system, could dictate target antigen specificity in SLE. Using genetic ablation of various TLRs in murine models of SLE, we have …


Molecular Classification And Prediction Of Metastatic Potential In Early Malignant Melanoma: Improvement Of Prognostic Accuracy By Quantitative In Situ Proteomic Analysis, Aaron J. Berger May 2006

Molecular Classification And Prediction Of Metastatic Potential In Early Malignant Melanoma: Improvement Of Prognostic Accuracy By Quantitative In Situ Proteomic Analysis, Aaron J. Berger

Yale Medicine Thesis Digital Library

The incidence of cutaneous malignant melanoma continues to increase every year, and remains the leading cause of skin cancer death in industrialized countries. In spite of the aggressive nature of advanced melanoma, there are no standard biological assays in clinical usage that can predict metastasis. This may be due, in part, to the inadequacy of reproducible assessment of protein expression using traditional immunohistochemistry. This dissertation will discuss the use of tissue microarrays combined with quantitative in situ molecular analysis of protein expression to allow prediction of melanoma metastasis. Through the identification and validation of novel prognostic biomarkers, we seek to …