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Specific Projects

(1) Transgenic mice conditionally expressing the mutant Braf oncogene using Cre-loxP system has been established. The process of carcinogenesis will be evaluated in these mice and those crossed with other genetically-engineered mice. Furthermore, enhancement of growth of thyroid cancer cells by fibroblasts, which is further augmented by irradiation, has been demonstrated in a rat model. The next step will be to expand this experimental approach to human cells, and involvement of microenvironment including fibroblasts to carcinogenesis will be studied.

(2) Enhancement of development of iodine-induced and spontaneous Hashimoto’ thyroiditis by low-dose irradiation has been confirmed in NOD-H2h4 mice. Involvement of IL-17-secreting Th17 cells in the pathogenesis of Hashimoto’ thyroiditis has also been demonstrated in these mice, but not in Graves’ disease in BALB/c mice. Anti-CD20 antibody has been shown to suppress development of Graves’ hyperthyroidism. Future study will be to evaluate the therapeutic effect of bortezomib and immune proteasome inhibitor on experimental thyroid autoimmune diseases.

(3) We identified a causative mutation in the patients with Nakajo-Nishimura syndrome. We will analyze the charactaristics of mutant protein in molecular, cellular and animal experiments.

(4) We reported high serum concentration of VEGF in the patients with RS3PE syndrome. We will confirm the association between high serum concentration of VEGF and platelet activation in these patients. It will provide us a new insight of platelet-mediated arthritis.

Current states and perspective

(1) Studies on development of mouse thyroid cancer models, molecular cloning of novel thyroid cancer-related oncogenes and relationship between cancer cells and microenvironments.

(2) Studies on the effects of radiation, various cytokines and immune-related molecules on autoimmune thyroid diseases such as Graves’disease and Hashimoto’s thyroiditis.

(3) Studies on the pathogenesis of autoinflammatory diseases, especially Nakajo-Nishimura syndrome, in order to establish a novel and effective therapeutic strategy such as molecular target drugs and various enzyme inhibitors.

(4) Studies on the cytokine profile of patient with Remitting Seronegative Symmetrical Synovitis with Pitting Edema (RS3PE) syndrome, in order to provide new diagnostic and therapeutic strategies against inflammatory arthritis.