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Takehito Uruno Last modified date:2022.06.16

Associate Professor / Division of Immunogenetics
Department of Immunobiology and Neuroscience
Medical Institute of Bioregulation




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Homepage
https://kyushu-u.pure.elsevier.com/en/persons/takehito-uruno
 Reseacher Profiling Tool Kyushu University Pure
Phone
092-642-6830
Fax
092-642-6829
Academic Degree
The University of Tokyo, Ph.D.
Country of degree conferring institution (Overseas)
No
Field of Specialization
Biological Chemistry, Molecular Cell Biology, Cancer biology, Pharmaceutical science
ORCID(Open Researcher and Contributor ID)
https://orcid.org/0000-0002-2812-9645
Total Priod of education and research career in the foreign country
09years00months
Research
Research Interests
  • Structure-function analysis of the DOCK family proteins and SULT2B1b.
    Development of novel molecular-targeted drugs for treating cancer, allergy, and immune diseases.
    keyword : cancer, immune system, signal transduction, cytoskeleton, drug development
    2009.05~2028.03.
Academic Activities
Papers
1. Tatsuguchi T, Uruno T, Sugiura Y, Sakata D, Izumi Y, Sakurai T, Hattori Y, Oki E, Kubota N, Nishimoto K, Oyama M, Kunimura K, Ohki T, Bamba T, Tahara H, Sakamoto M, Nakamura M, Suematsu M, Fukui Y., Cancer-derived cholesterol sulfate is a key mediator to prevent tumor infiltration by effector T cells, INTERNATIONAL IMMUNOLOGY, 10.1093/intimm/dxac002, 34, 5, 277-289, 2022.04, 本研究は、大腸癌臨床検体及びマウスの移植がんモデルを用いて、がん細胞によって産生されるコレステロール硫酸がリンパ球の腫瘍内浸潤を抑制してがんの免疫回避に寄与していることを明らかにした。.
2. Tetsuya Sakurai, Mutsuko Kukimoto-Niino, Kazufumi Kunimura, Nana Yamane, Daiji Sakata, Ryosuke Aihara, Tomoharu Yasuda, Shigeyuki Yokoyama, Mikako Shirouzu, Yoshinori Fukui, Takehito Uruno*, A conserved PI(4,5)P2–binding domain is critical for immune regulatory function of DOCK8, Life Science Alliance, 10.26508/lsa.202000873, 2021.02, DOCK8 is a Cdc42-specific guanine-nucleotide exchange factor that is essential for development and functions of various subsets of leukocytes in innate and acquired immune responses. Although DOCK8 plays a critical role in spatial control of Cdc42 activity during interstitial leukocyte migration, the mechanism remains unclear. We show that the DOCK homology region (DHR)-1 domain of DOCK8 binds specifically to phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and is required for its recruitment to the plasma membrane. Structural and biochemical analyses reveal that DOCK8 DHR-1 domain consists of a C2 domain-like core with loops creating the upper surface pocket, where three basic residues are located for stereospecific recognition of phosphoinositides. Substitution of the two basic residues, K576 and R581, with alanine abolished PI(4,5)P2 binding in vitro, ablated the ability of DOCK8 to activate Cdc42 and support leukocyte migration in three-dimensional collagen gels. Dendritic cells carrying the mutation exhibited defective interstitial migration in vivo. Thus, our study uncovers a critical role of DOCK8 in coupling PI(4,5)P2 signaling with Cdc42 activation for immune regulation..
3. Tetsuya Sakurai, Takehito Uruno, Yuki Sugiura, Takaaki Tatsuguchi, Kazuhiko Yamamura, Miho Ushijima, Yuko Hattori, Mutsuko Kukimoto-Niino, Chiemi Mishima-Tsumagari, Mayuki Watanabe, Makoto Suematsu, Yoshinori Fukui, Cholesterol sulfate is a DOCK2 inhibitor that mediates tissue-specific immune evasion in the eye, Science Signaling, 10.1126/scisignal.aao4874, 11, 541, 2018.07, Although immune responses are essential to protect the body from infection, they can also harm tissues. Certain tissues and organs, including the eye, constitute specialized microenvironments that locally inhibit immune reactivity. Dedicator of cytokinesis protein 2 (DOCK2) is a Rac-specific guanine nucleotide exchange factor (GEF) that is predominantly found in hematopoietic cells. DOCK2 plays a key role in immune surveillance because it is essential for the activation and migration of leukocytes. DOCK2 mutations cause severe immunodeficiency in humans. We found that DOCK2-mediated Rac activation and leukocyte migration were effectively inhibited by cholesterol sulfate (CS), but not by cholesterol or other sulfated steroids. CS bound to the catalytic domain of DOCK2 and suppressed its GEF activity. Mass spectrometric quantification revealed that CS was most abundantly produced in the Harderian gland, which provides the lipids that form the oily layer of the tear film. Sulfation of cholesterol is mediated by the sulfotransferases SULT2B1b and, to a lesser extent, SULT2B1a, which are produced from the same gene through alternative splicing. By genetically inactivating Sult2b1, we showed that the lack of CS in mice augmented ultraviolet- and antigen-induced ocular surface inflammation, which was suppressed by administration of eye drops containing CS. Thus, CS is a naturally occurring DOCK2 inhibitor and contributes to the generation of the immunosuppressive microenvironment in the eye..
Membership in Academic Society
  • The Japanese Biochemical Society
Awards
  • Role of the Rac activator DOCK1 in pancreatic cancer development and its therapeutic use
Educational
Other Educational Activities
  • 2021.07.
  • 2017.11.