Transplant Models

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As noted in the goals and objectives stated for this project, it aims to create new models that test distinct hypotheses and provide new understandings for development of novel strategies in the treatment of lymphoma, myeloma, leukemia, breast cancer and renal cancer by hematopoietic stem cell transplantation. Hematopoietic stem cell transplant treatment of these diseases generally results in lymphopenia and immune compromise. The observation that in humans there is the ability to upregulate thymus function in the setting of cancer therapy-associated lymphopenia has been translated to murine models. We have initiated four parallel efforts to identify points of control in thymus function. In experiments utilizing KGF, which was found to upregulate thymus activity, we observed that while thymocyte precursor pool size and molecules involved in migration are not affected, the critical control point at the level of thymus epithelial cells are affected such that this cell population increases proliferation and total number thereby increasing niches for thymocyte maturation and overall thymopoiesis.