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Research | Core Facilities | Patient Studies | Tech Transfer | Seminars | Intranet | Careers | Search | Contact Us | Ways To Give HOME |
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More about
Dr. Webb 101 Immunobiology and Cancer Research Program
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Research Interests Several years ago, we discovered that Bright associates with Bruton’s tyrosine kinase, or Btk. Btk was identified as the defective kinase in X-linked immunodeficiency diseases in both mice and humans. X-linked agammaglobulinemia primarily affects boys and is characterized by blocks in B-cell development that result in abnormally low production of B lymphocytes and serum immunoglobulin. Immunodeficient patients are treated with intravenous immunoglobulin to ward off infections. Although the specific genetic defect of this disease was identified in 1993, the underlying mechanisms that lead to early blocks in B-cell development remain unclear. Our experiments indicate that the ability of Bright to activate transcription of an immunoglobulin promoter in vitro critically requires both Btk and another protein that is a substrate for Btk. These data provide a direct link between Btk function and immunoglobulin expression. Furthermore, studies using transgenic mice that express a dominant negative form of Bright in B cells suggest that the transgenic mice share characteristics with Btk deficient mice. These data suggest that Bright functions in the same molecular pathway as Btk. Because Btk deficiency results in a more severe phenotype in man than in mice, we are using retroviral transduction to determine the effects of dominant negative Bright on human B-cell progenitors. In addition, transgenic mice that over-express wild type Bright were generated and resulted in mice with an autoimmune phenotype that resembles lupus. Data from these mice has helped to define specific stages in B-cell development important for maintenance of B-cell tolerance. Studies to explore the effects of Bright over-expression in human systems on antibody production are also in progress. The long-term goal of these studies is to develop a better understanding of the mechanisms controlling immunoglobulin production so that new drugs can be developed to treat both autoimmune and immunodeficiency diseases. Joined OMRF Scientific Staff in 1990. Mailing Address
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