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Uruno Takehito Last modified date:2024.02.08

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

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Frontiers in Immunology, Guest reviewer .
Academic Degree
The University of Tokyo, Ph.D.
Country of degree conferring institution (Overseas)
Field of Specialization
Biological Chemistry, Immunology, Cancer biology, Metabolites, Pharmaceutical science
ORCID(Open Researcher and Contributor ID)
Total Priod of education and research career in the foreign country
Research Interests
  • Immune regulation of diseases and metabolites:
    Structure-function analysis of the DOCK family proteins and SULTs.
    Development of novel molecular-targeted drugs for treating cancer, allergy, and immune diseases.
    Metabolite Biology
    keyword : cancer, immune system, signal transduction, cytoskeleton, drug development
Academic Activities
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, 4, 4, e202000873-e202000873, 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..
1. Takehito Uruo, Takaaki Tatsuguchi, Yuki Sugiura, Yoshinori Fukui, A tumor metabolite impacting immunotherapy efficacy: Cholesterol sulfate regulates tumor-immune interactions, Keystone Symposia on "Cancer Immunotherapy: Mechanisms of Response versus Resistance", 2023.03, Tumors constitute an ecosystem of heterogeneous metabolic environments where a variety of metabolites function as intra- and intercellular mediators that affect tumor development. We previously identified that cholesterol sulfate (CS) is an endogenous inhibitor of DOCK2, a Rac activator essential for leukocyte migration and activation. Thereby, local CS production creates immune-evasive/immunosuppressive microenvironments. Many types of human cancers express the SULT2B1 gene, encoding the steroid sulfotransferase SULT2B1b responsible for CS production, and in certain cancers, the gene expression associates with poor prognosis. In colon cancers, level of CS is higher in tumor tissues, and tumor regions with high CS were poorly infiltrated with CD8+ T cells. In syngeneic mouse models, CS-producing cancer cells formed larger tumors in a host-immunity-dependent manner, and exhibited resistance to immunotherapies via antigen-specific T cell transfer and immune-checkpoint blockade. A novel SULT2B1b inhibitor we identified counteracted the above phenotypes. Thus, cancer-derived CS is a key mediator of tumor-immune interactions, and CS/SULT2B1b may be a potential target for enhancing the efficacy of immunotherapies..
Membership in Academic Society
  • The Japanese Biochemical Society
Other Educational Activities
  • 2021.07.
  • 2017.11.