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Immunologic mechanisms are involved in the onset and progression of almost all clinically important diseases. Our research goal is to understand basic immunologic mechanisms, and apply such knowledge to the development of effective therapies. Research projects currently underway include the following:

1. Role of major histocompatibility complex (MHC) class I-like molecules in health and disease.  

We have recently identified novel stress-inducible MHC class I-like molecules that serve as ligands for the activating natural killer cell receptor NKG2D. Evidence is emerging that they play a key role in immunosurveillance and that their aberrant expression results in autoimmune disorders.

Representative publications: 

Yoshida, S., Mohamed, R. H., Kajikawa, M., Koizumi, J., Tanaka, M., Fugo, K., Otsuka, N., Maenaka, K., Yagita, H., Chiba, H. and Kasahara, M. Involvement of an NKG2D ligand H60c in epidermal dendritic T cell-mediated wound repair. J. Immunol. 188, 3972-3979 (2012).

Takada, A., Yoshida, S., Kajikawa, M., Miyatake, Y., Tomaru, U., Sakai, M., Chiba, H., Maenaka, K., Kohda, D., Fugo, K. and Kasahara, M. Two novel NKG2D ligands of the mouse H60 family with differential expression patterns and binding affinities to NKG2D. J. Immunol. 180, 1678-1685 (2008).

2. Role of thymoproteasomes in health and disease. Thymoproteasomes are a specialized type of proteasomes implicated in positive selection of T cells in the thymus. Their function is being studied using transgenic and knock-out mice.

Representative publications:

Tomaru, U., Takahashi, S., Ishizu, A., Miyatake, Y., Gohda, A., Suzuki, S., Ono, A., Ohara, J., Baba, T., Murata, S., Tanaka, K. and Kasahara, M.  Decreased proteasomal activity causes age-related phenotypes and promotes the development of metabolic abnormalities.  Am. J. Pathol. 180, 963-972 (2012).

Tomaru, U, Ishizu, A., Murata, S., Miyatake, Y., Suzuki, S., Takahashi, S., Kazamaki, T., Ohara, J., Baba, T., Iwasaki, S., Fugo, K., Otsuka, N., Tanaka, K. and Kasahara, M.  Exclusive expression of proteasome subunit β5t in the human thymic cortex.  Blood 113, 5186-5191 (2009).

3. Cancer cells and their microenvironments. We have discovered that simple coculture with feeder cells alters the properties and behaviors of adult T-cell leukemia/lymphoma cells. We are using this coculture system to analyze the interactions of cancer cells and their microenvironment.

Representative publication:

Miyatake, Y., Oliveira, A. L. A., Jarboui, M. A., Ota, S., Tomaru, U., Teshima, T., Hall, W. W. and Kasahara, M. Protective roles of epithelial cells in the survival of adult T-cell leukemia/lymphoma cells.  Am. J. Pathol. 182, 1832-1842 (2013).

4. Structure and function of variable lymphocyte receptors (VLR). VLRs are antigen receptors discovered in primitive vertebrates; unlike immunoglobulins or T-cell receptors, they generate diversity by combining leucine-rich repeat modules. We are analyzing the structure and functions of VLR.

Representative publications:

Kasahara, M. and Sutoh, Y. Two forms of adaptive immunity in vertebrates: similarities and differences. Adv. Immunol. 122, 59-90 (2014).

Boehm, T., McCurley, N., Sutoh, Y., Schorpp, M., Kasahara, M. and Cooper, M. D. VLR-based adaptive immunity. Annu. Rev. Immunol. 30, 203-220 (2012).

Kasamatsu, J., Sutoh, Y., Fugo, K., Otsuka, N., Iwabuchi, K. and Kasahara, M. Identification of a third variable lymphocyte receptor in the lamprey. Proc. Natl. Acad. Sci. USA 107, 14304-14308 (2010).