Laboratory of Molecular Medicine
MATSUMOTO Naoki Assoc. Prof. Ph.D.
Immunology of Innate Immune cells
Major histocompatibility complex
Here, I would like to briefly introduce my research career.
＠Graduate School of Pharmaceutical Sciences, the University of Tokyo
I started my research career as a grad student in Graduate School of Pharmaceutical Sciences, the University of Tokyo. My study in grad school focused on intracellular signal transduction during activation of lymphocytes. I identified a protein that is phosphorylated in T lymphocytes activated by Concanavalin A. I purified the protein, determined partial amino acid sequences of the protein, and cloned the cDNA encoding the protein. The identified is a protein, named LSP11~3.
@Institute of Medical Sciences, the University of Tokyo (IMSUT)
After getting PhD, I joined Department of Parasitology in IMSUT, which was organized by Pr. Some KOJIMA. Upon infection with helminth, which is a general name for multicellular parasites, infected individuals develop Th2-type immune response characterized by increase of serum IgE concentration and number of eosinophils. I studied how and why helminth infection causes strong Th2-type immune response, focusing on helminth antigens.
@Washington University School of Medicine in St. Louis
I took a leave of absence from IMSUT and had an opportunity to study in Wayne M. Yokoyama laboratory in Washington University School of Medicine in St. Louis. Professor Yokoyama found that a NK cell receptor Ly49 recognizes MHC class I molecules on target cells, which inhibits NK cell killing of the target cells. Ly49 has a structure similar to C-type lectin, a family of proteins that bind glycans and involvement of glycans on MHC class I molecules in Ly49 recognition of MHC class I was one of the topics. I showed that Ly49 recognizes MHC class I molecules, independent of glycans on MHC class I4.
＠Graduate School of Frontier Sciences, the University of Tokyo (GSFS)
After coming back from the US, I got a faculty position in GSFS and continued to study the Ly49 project. Together with three grad students, we identified the region of a MHC class I molecule recognized by Ly495,6 and the region of the HLA-E molecule recognized by human NK cell receptor CD94/NKG27, and created short circular peptides that inhibit Ly49 – MHC class I interaction and induce killing of MHC class I-expressing target cells, potential anti-tumor drugs8. We also found that KLRG1, an inhibitory receptor on NK cells and T cells, recognizes three classical cadherins and inhibit NK cell killing of E-cadherin-expressing tumor cells9. The NK cells receptors, such as Ly49, CD94/NKG2, and KLRG1, have structure similar to C-type lectins and are encoded in a genomic region called NK-gene complex. Progress of genome research revealed that gene for many C-type lectin receptors expressed on myeloid cells also make clusters in adjacent to the NK-gene complex, which prompted us to study the C-type lectin receptors on myeloid cells. We established monoclonal antibodies that specifically recognize each of the receptors and identified the cell populations that express each of the receptors10-13. We also found that one of the receptors, DCIR2, recognizes N-glycans with a unique bisecting GlcNAc structure14.
1) J. Biochem. 113: 630, 2) J. Biochem.117: 222, 3) J. Biochem. 118: 237, 4) Immunity 8: 245, 5) J. Exp. Med. 193: 147, 6) Int. Immunol. 16: 197, 7) Eur. J. Immunol. 34: 81, 8) Int. Immunol. 16: 385, 9) J. Exp. Med. 203: 289, 10) Biochem Biophys Res. Com. 467: 383, 11) Biochem Biophys Res Com. 480: 215, 12) Biochem Biophys Res Com. 494:440, 13) Biochem Biophys Rep 24: 100840, 14) J Biol Chem. 288:33598
|1999 - Present Associate Professor, Laboratory of Molecular Medicine, Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo|
|1995 - 1998 Postdoctoral fellow, Washington University School of Medicine in St. Louis|
|1991 - 1999 Research Associate, Institute of Medical Sciences, The University of Tokyo|
|1991 Ph. D. Graduate School of Pharmaceutical Sciences, The University of Tokyo|
|1988 M. Sc. Graduate School of Pharmaceutical Sciences, The University of Tokyo|
|1986 B. Sc. Department of Pharmaceutical Sciences, The University of Tokyo|