Faculty Profiles - URUNO TAKEHITO

Information

写真a

URUNO TAKEHITO

Organization

Medical Institute of Bioregulation Department of Immunobiology and Neuroscience Associate Professor
Graduate School of Medical Sciences Department of Medicine（Concurrent）
Graduate School of Medical Sciences Department of Medical Sciences（Concurrent）

Tel

0926426830

Homepage

https://loop.frontiersin.org/people/479156/overview
Frontiers in Immunology, Guest reviewer

External link

Research Areas

Life Science / Functional biochemistry
Life Science / Medical biochemistry

Degree

The University of Tokyo, Ph.D.

Research History

通産省工業技術院生命工学工業技術研究所（1994~1999）、アメリカ赤十字社ホランド研究所（1999~2004）、アメリカ国立衛生研究所／NIH（2004~2008）、理化学研究所CDB（2008~2009）、九州大学生体防御医学研究所免疫遺伝学分野（特任講師、2009~2013）、九州大学生体防御医学研究所免疫遺伝学分野（助教、2013~2014）、2014年2月〜現職「細胞生理応答研究から新しい創薬につながる研究を目指します」「次世代の若い研究者に、世界基準の研究価値観を期待します」

通産省工業技術院生命工学工業技術研究所（1994~1999）、アメリカ赤十字社ホランド研究所（1999~2004）、アメリカ国立衛生研究所／NIH（2004~2008）、理化学研究所CDB（2008~2009）、九州大学生体防御医学研究所免疫遺伝学分野（特任講師、2009~2013）、九州大学生体防御医学研究所免疫遺伝学分野（助教、2013~2014）、2014年2月〜現職「細胞生理応答研究から、新しい創薬につながる研究を目指しています」「次世代の日本の若い研究者に、世界基準の研究価値観を期待しています」
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Research Interests・Research Keywords

Research theme：Immune control of disease

Keyword：Immune control of disease

Research period： 2024
Research theme：Biochemistry

Keyword：Biochemistry

Research period： 2024
Research theme：Metabolites, bioactive substances

Keyword：Metabolites, bioactive substances

Research period： 2024
Research theme：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

Research period： 2009.5 - 2033.3

Awards

内藤記念科学奨励金・研究助成

2017.9 公益財団法人内藤記念科学振興財団

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膵臓がんにおけるRac活性化因子DOCK1の機能解析とその選択的阻害による治療

Papers

Cancer-derived cholesterol sulfate is a key mediator to prevent tumor infiltration by effector T cells Reviewed International journal

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.

INTERNATIONAL IMMUNOLOGY 34 ( 5 ) 277 - 289 2022.4 （ ISSN:0953-8178 eISSN:1460-2377 ）

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Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Oxford University Press (OUP)

<title>Abstract</title>
Effective tumor immunotherapy requires physical contact of T cells with cancer cells. However, tumors often constitute a specialized microenvironment that excludes T cells from the vicinity of cancer cells, and its underlying mechanisms are still poorly understood. DOCK2 is a Rac activator critical for migration and activation of lymphocytes. We herein show that cancer-derived cholesterol sulfate (CS), a lipid product of the sulfotransferase SULT2B1b, acts as a DOCK2 inhibitor and prevents tumor infiltration by effector T cells. Using clinical samples, we found that CS was abundantly produced in certain types of human cancers such as colon cancers. Functionally, CS-producing cancer cells exhibited resistance to cancer-specific T-cell transfer and immune checkpoint blockade. Although SULT2B1b is known to sulfate oxysterols and inactivate their tumor-promoting activity, the expression levels of cholesterol hydroxylases, which mediate oxysterol production, are low in SULT2B1b-expressing cancers. Therefore, SULT2B1b inhibition could be a therapeutic strategy to disrupt tumor immune evasion in oxysterol-non-producing cancers. Thus, our findings define a previously unknown mechanism for tumor immune evasion and provide a novel insight into the development of effective immunotherapies.

DOI： 10.1093/intimm/dxac002

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Cholesterol sulfate is a DOCK2 inhibitor that mediates tissue-specific immune evasion in the eye Reviewed International journal

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

Science Signaling 11 ( 541 ) 2018.7

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Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1126/scisignal.aao4874
A conserved PI(4,5)P2–binding domain is critical for immune regulatory function of DOCK8 Reviewed International journal

4 ( 4 ) e202000873 - e202000873 2021.2

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Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.26508/lsa.202000873
Targeting Ras-Driven Cancer Cell Survival and Invasion through Selective Inhibition of DOCK1. Reviewed

Takehito Uruno

Cell reports 2017.5

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Authorship：Lead author Language：Others Publishing type：Research paper (scientific journal)

DOI： 10.1016/j.celrep.2017.04.016
The transcription factor EPAS1 links DOCK8 deficiency to atopic skin inflammation via IL-31 induction. Reviewed

Takehito Uruno

Nature communications 2017.1

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Language：Others Publishing type：Research paper (scientific journal)

DOI： 10.1038/ncomms13946
Activation of Arp2/3 complex-mediated actin polymerization by cortactin Reviewed

URUNO T

Nat. Cell Biol. 3 259 - 266 2001.3

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Authorship：Lead author Language：Others Publishing type：Research paper (scientific journal)

Activation of Arp2/3 complex-mediated actin polymerization by cortactin.
Cortactin, a filamentous actin (F-actin)-associated protein and prominent substrate of Src, is implicated in progression of breast tumours through gene amplification at chromosome 11q13. However, the function of cortactin remains obscure. Here we show that cortactin co-localizes with the Arp2/3 complex, a de novo actin nucleator, at dynamic particulate structures enriched with actin filaments. Cortactin binds directly to the Arp2/3 complex and activates it to promote nucleation of actin filaments. The interaction of cortactin with the Arp2/3 complex occurs at an amino-terminal domain that is rich in acidic amino acids. Mutations in a conserved amino-acid sequence of DDW abolish both the interaction with the Arp2/3 complex and complex activation. The N-terminal domain is not only essential but also sufficient to target cortactin to actin-enriched patches within cells. Interestingly, the ability of cortactin to activate the Arp2/3 complex depends on an activity for F-actin binding, which is almost 20-fold higher than that of the Arp2/3 complex. Our data indicate a new mechanism for activation of actin polymerization involving an enhanced interaction between the Arp2/3 complex and actin filaments.

DOI： 10.1038/35060051
DOCK2 regulates MRGPRX2/B2-mediated mast cell degranulation and drug-induced anaphylaxis Reviewed

Kazufumi Kunimura, Sayaka Akiyoshi, Takehito Uruno, Keisuke Matsubara, Daiji Sakata, Kenji Morino, Kenichiro Hirotani, Yoshinori Fukui

Journal of Allergy and Clinical Immunology 151 ( 6 ) 1585 - 1594.e9 2023.6 （ ISSN:0091-6749 eISSN:1097-6825 ）

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Background: Drug-induced anaphylaxis is triggered by the direct stimulation of mast cells (MCs) via Mas-related G protein–coupled receptor X2 (MRGPRX2; mouse ortholog MRGPRB2). However, the precise mechanism that links MRGPRX2/B2 to MC degranulation is poorly understood. Dedicator of cytokinesis 2 (DOCK2) is a Rac activator predominantly expressed in hematopoietic cells. Although DOCK2 regulates migration and activation of leukocytes, its role in MCs remains unknown. Objective: We aimed to elucidate whether—and if so, how—DOCK2 is involved in MRGPRX2/B2-mediated MC degranulation and anaphylaxis. Methods: Induction of drug-induced systemic and cutaneous anaphylaxis was compared between wild-type and DOCK2-deficient mice. In addition, genetic or pharmacologic inactivation of DOCK2 in human and murine MCs was used to reveal its role in MRGPRX2/B2-mediated signal transduction and degranulation. Results: Induction of MC degranulation and anaphylaxis by compound 48/80 and ciprofloxacin was severely attenuated in the absence of DOCK2. Although calcium influx and phosphorylation of several signaling molecules were unaffected, MRGPRB2-mediated Rac activation and phosphorylation of p21-activated kinase 1 (PAK1) were impaired in DOCK2-deficient MCs. Similar results were obtained when mice or MCs were treated with small-molecule inhibitors that bind to the catalytic domain of DOCK2 and inhibit Rac activation. Conclusion: DOCK2 regulates MRGPRX2/B2-mediated MC degranulation through Rac activation and PAK1 phosphorylation, thereby indicating that the DOCK2-Rac-PAK1 axis could be a target for preventing drug-induced anaphylaxis.

DOI： 10.1016/j.jaci.2023.01.029

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がん免疫療法に対する抵抗性を付与する腫瘍メタボライト Reviewed

宇留野武人, 竜口崇明, 杉浦悠毅, 福井宣規

日本がん免疫学会総会プログラム・抄録集 27回 173 - 173 2023.6

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Authorship：Lead author,　Corresponding author Language：Japanese Publisher：日本がん免疫学会

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Cholesterol sulfate limits neutrophil recruitment and gut inflammation during mucosal injury. Reviewed International journal

Kenji Morino, Kazufumi Kunimura, Yuki Sugiura, Yoshihiro Izumi, Keisuke Matsubara, Sayaka Akiyoshi, Rae Maeda, Kenichiro Hirotani, Daiji Sakata, Seiya Mizuno, Satoru Takahashi, Takeshi Bamba, Takehito Uruno, Yoshinori Fukui

Frontiers in immunology 14 1131146 - 1131146 2023.3 （ ISSN:1664-3224 ）

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Language：English Publishing type：Research paper (scientific journal)

During mucosal injury, intestinal immune cells play a crucial role in eliminating invading bacteria. However, as the excessive accumulation of immune cells promotes inflammation and delays tissue repair, it is essential to identify the mechanism that limits the infiltration of immune cells to the mucosal-luminal interface. Cholesterol sulfate (CS) is the lipid product of the sulfotransferase SULT2B1 and suppresses immune reactions by inhibiting DOCK2-mediated Rac activation. In this study, we aimed to elucidate the physiological role of CS in the intestinal tract. We found that, in the small intestine and colon, CS is predominantly produced in the epithelial cells close to the lumen. While dextran sodium sulfate (DSS)-induced colitis was exacerbated in Sult2b1-deficient mice with increased prevalence of neutrophils, the elimination of either neutrophils or intestinal bacteria in Sult2b1-deficient mice attenuated disease development. Similar results were obtained when the Dock2 was genetically deleted in Sult2b1-deficient mice. In addition, we also show that indomethacin-induced ulcer formation in the small intestine was exacerbated in Sult2b1-deficient mice and was ameliorated by CS administration. Thus, our results uncover that CS acts on inflammatory neutrophils, and prevents excessive gut inflammation by inhibiting the Rac activator DOCK2. The administration of CS may be a novel therapeutic strategy for inflammatory bowel disease and non-steroidal anti-inflammatory drug-induced ulcers.

DOI： 10.3389/fimmu.2023.1131146

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コレステロール関連代謝産物と疾患制御コレステロール硫酸は白血球の遊走制御を介して眼の免疫特権環境の形成に寄与する Invited Reviewed

國村和史, 宇留野武人, 杉浦悠毅, 福井宣規

日本生化学会大会プログラム・講演要旨集 95回 2S01e - 04 2022.11

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Language：Japanese Publisher：(公社)日本生化学会

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Identification of a functional DOCK8 gene polymorphism associated with atopic dermatitis Reviewed International journal

Kazufumi Kunimura, Kazuhiko Yamamura, Takeshi Nakahara, Makiko Kido-Nakahara, Takehito Uruno, Yoshinori Fukui

Allergy 77 ( 12 ) 3670 - 3672 2022.7 （ ISSN:0105-4538 eISSN:1398-9995 ）

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1111/all.15429

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癌由来のコレステロール硫酸はエフェクターT細胞の腫瘍浸潤を防ぐ重要なメディエーターである(Cancer-derived cholesterol sulfate is a key mediator to prevent tumor infiltration by effector T cells) Reviewed

Tatsuguchi Takaaki, Uruno Takehito, Sugiura Yuki, Sakata Daiji, Izumi Yoshihiro, Sakurai Tetsuya, Hattori Yuko, Oki Eiji, Kubota Naoto, Nishimoto Koshiro, Oyama Masafumi, Kunimura Kazufumi, Ohki Takuto, Bamba Takeshi, Tahara Hideaki, Sakamoto Michiie, Nakamura Masafumi, Suematsu Makoto, Fukui Yoshinori

International Immunology 34 ( 5 ) 277 - 289 2022.5 （ ISSN:0953-8178 ）

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Authorship：Lead author,　Corresponding author Language：English Publisher：Oxford University Press

腫瘍微小環境へのエフェクターT細胞の浸潤を排除するメカニズムの解明を試みた。硫酸基転移酵素SULT2B1bによって生成される癌由来のコレステロール硫酸(CS)がRac活性化因子DOCK2を阻害し、エフェクターT細胞の腫瘍浸潤を阻害することが明らかになった。臨床サンプルを用いて、CSが大腸癌などの特定の種類のヒト癌で豊富に産生されていることを見出した。機能的には、CSを産生する癌細胞は、癌特異的T細胞移植や免疫チェックポイント阻害に対して抵抗性を示した。SULT2B1bはオキシステロールを硫酸化し、その腫瘍促進活性を不活性化することが知られているが、SULT2B1bを発現する癌ではオキシステロール産生を媒介するコレステロール水酸化酵素の発現量が低かった。したがって、SULT2B1bの阻害は、オキシステロール非産生癌の腫瘍免疫回避を妨害する治療戦略となる可能性があった。以上より、新たな腫瘍の免疫回避のメカニズムを明らかになり、効果的な免疫療法の開発に新たな知見が得られた。
Pharmacological intervention of cholesterol sulfate-mediated T cell exclusion promotes antitumor immunity Reviewed International journal

Takaaki Tatsuguchi, Takehito Uruno, Yuki Sugiura, Kounosuke Oisaki, Daisuke Takaya, Daiji Sakata, Yoshihiro Izumi, Takaya Togo, Yuko Hattori, Kazufumi Kunimura, Testuya Sakurai, Teruki Honma, Takeshi Bamba, Masafumi Nakamura, Motomu Kanai, Makoto Suematsu, Yoshinori Fukui

Biochemical and Biophysical Research Communications 609 183 - 188 2022.4 （ ISSN:0006-291X eISSN:1090-2104 ）

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Authorship：Lead author,　Corresponding author Language：Others Publishing type：Research paper (scientific journal) Publisher：Elsevier BV

DOI： 10.1016/j.bbrc.2022.04.035

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DOCK8 deficiency causes a skewing to type 2 immunity in the gut with expansion of group 2 innate lymphoid cells Reviewed International journal

Matsubara K, Kunimura K, Yamane N, Aihara R, Sakurai T, Sakata D, Uruno T, Fukui Y.

Biochem Biophys Res Commun. 559 135 - 140 2021.6

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Language：English

DOI： 10.1016/j.bbrc.2021.04.094.
Targeted inhibition of EPAS1–driven IL-31 production by a small-molecule compound Reviewed

2021.4

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Language：Others Publishing type：Research paper (scientific journal)

DOI： 10.1016/j.jaci.2021.03.029
DOCK8 controls survival of group 3 innate lymphoid cells in the gut through Cdc42 activation Reviewed International journal

Ryosuke Aihara, Kazufumi Kunimura, Mayuki Watanabe, Takehito Uruno, Nana Yamane, Tetsuya Sakurai, Daiji Sakata, Fusanori Nishimura, Yoshinori Fukui

International Immunology 2020.9

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1093/intimm/dxaa066
S100A4 Protein Is Essential for the Development of Mature Microfold Cells in Peyer’s Patches Reviewed International journal

29 ( 9 ) 2823 - 2834 2019.11

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Intestinal microfold cells (M cells) in Peyer's patches are a special subset of epithelial cells that initiate mucosal immune responses through uptake of luminal antigens. Although the cytokine receptor activator of nuclear factor-κB ligand (RANKL) expressed on mesenchymal cells triggers differentiation into M cells, other environmental cues remain unknown. Here, we show that the metastasis-promoting protein S100A4 is required for development of mature M cells. S100A4-producing cells are a heterogenous cell population including lysozyme-expressing dendritic cells and group 3 innate lymphoid cells. We found that in the absence of DOCK8, a Cdc42 activator critical for interstitial leukocyte migration, S100A4-producing cells are reduced in the subepithelial dome, resulting in a maturation defect of M cells. While S100A4 promotes differentiation into mature M cells in organoid culture, genetic inactivation of S100a4 prevents the development of mature M cells in mice. Thus, S100A4 is a key environmental cue that regulates M cell differentiation in collaboration with RANKL.

DOI： 10.1016/j.celrep.2019.10.091
Selective role of neurokinin B in IL-31-induced itch response in mice. Reviewed

Takehito Uruno

The Journal of allergy and clinical immunology 144 ( 4 ) 1130 - 1133.e8 2019.8

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DOI： 10.1016/j.jaci.2019.06.031
The Rac Activator DOCK2 Mediates Plasma Cell Differentiation and IgG Antibody Production. Reviewed International journal

Takehito Uruno

Frontiers in immunology 9 243 - 243 2018.2

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Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)

DOI： 10.3389/fimmu.2018.00243
DOCK1 inhibition suppresses cancer cell invasion and macropinocytosis induced by self-activating Rac1P29S mutation. Reviewed

Takehito Uruno

Biochemical and biophysical research communications 2018.2

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Authorship：Last author,　Corresponding author Language：Others Publishing type：Research paper (scientific journal)

DOI： 10.1016/j.bbrc.2018.02.073
Thymic epithelial cell-specific deletion of Jmjd6 reduces Aire protein expression and exacerbates disease development in a mouse model of autoimmune diabetes. Reviewed

Takehito Uruno

Biochemical and biophysical research communications 2017.5

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DOI： 10.1016/j.bbrc.2017.05.113
DOCK8 Protein Regulates Macrophage Migration through Cdc42 Protein Activation and LRAP35a Protein Interaction. Reviewed

Takehito Uruno

The Journal of biological chemistry 2016.12

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Language：Others Publishing type：Research paper (scientific journal)

DOI： 10.1074/jbc.M116.736306
Intronic regulation of Aire expression by Jmjd6 for self-tolerance induction in the thymus. Reviewed

Takehito Uruno

Nature communications 2015.11

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Language：Others Publishing type：Research paper (scientific journal)

DOI： 10.1038/ncomms9820
DOCK2 and DOCK5 Act Additively in Neutrophils To Regulate Chemotaxis, Superoxide Production, and Extracellular Trap Formation Reviewed International journal

Mayuki Watanabe, Masao Terasawa, Kei Miyano, Toyoshi Yanagihara, Takehito Uruno, Fumiyuki Sanematsu, Akihiko Nishikimi, Jean Francois Cote, Hideki Sumimoto, Yoshinori Fukui

JOURNAL OF IMMUNOLOGY 193 ( 11 ) 2014.12

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.4049/jimmunol.1400885
DOCK5 functions as a key signaling adaptor that links Fc epsilon RI signals to microtubule dynamics during mast cell degranulation Reviewed International journal

Kana Ogawa, Yoshihiko Tanaka, Takehito Uruno, Duan Xuefeng, Yosuke Harada, Fumiki Sanematsu, Kazuhiko Yamamura, Masao Terasawa, Akihiko Nishikimi, Jena Francois Cote, Yoshinori Fukui

JOURNAL OF EXPERIMENTAL MEDICINE 211 ( 7 ) 2014.6

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1084/jem.20131926
Dimerization of DOCK2 is essential for DOCK2-mediated Rac activation and lymphocyte migration. Reviewed

Takehito Uruno

PloS one 2012.9

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Authorship：Lead author Language：Others Publishing type：Research paper (scientific journal)

DOI： 10.1371/journal.pone.0046277
Blockade of inflammatory responses by a small-molecule inhibitor of the Rac activator DOCK2. Reviewed International journal

Takehito Uruno

Chemistry & biology 19 ( 4 ) 488 - 97 2012.4

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Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1016/j.chembiol.2012.03.008
DOCK8は免疫反応時の間質樹状細胞遊走に重要なCdc42アクチベータである Reviewed

日本免疫学会総会・学術集会記録 41 2012.3

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DOI： 10.1182/blood-2012-01-407098
Racグアニンヌクレオチド交換因子DOCK2及びそのパートナーELMO1のそれらの自己阻害化形からの相互排除のための構造的基盤 Reviewed

109 ( 9 ) 2012.2

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Language：Others Publishing type：Research paper (scientific journal)

DOI： 10.1073/pnas.1113512109
Molecular basis for barbed end uncapping by CARMIL homology domain 3 of mouse CARMIL-1. Reviewed

Takehito Uruno

The Journal of biological chemistry 2010.7

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Authorship：Lead author Language：Others Publishing type：Research paper (scientific journal)

DOI： 10.1074/jbc.M110.134221
Selective control of type I IFN induction by the Rac activator DOCK2 during TLR-mediated plasmacytoid dendritic cell activation. Reviewed International journal

Takehito Uruno

The Journal of experimental medicine 207 ( 4 ) 721 - 30 2010.3

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1084/jem.20091776
Purification of capping protein using the capping protein binding site of CARMIL as an affinity matrix. Reviewed

Takehito Uruno

Protein expression and purification 2009.5

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Language：Others Publishing type：Research paper (scientific journal)

DOI： 10.1016/j.pep.2009.05.002
CARMIL is a potent capping protein antagonist: identification of a conserved CARMIL domain that inhibits the activity of capping protein and uncaps capped actin filaments. Reviewed

Takehito Uruno

The Journal of biological chemistry 2006.1

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Authorship：Lead author Language：Others Publishing type：Research paper (scientific journal)

DOI： 10.1074/jbc.m513186200, 10.1074/jbc.M513186200
Interaction of cortactin and Arp2/3 complex is required for sphingosine-1-phosphate-induced endothelial cell remodeling. Reviewed

Takehito Uruno

Experimental cell research 2004.8

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DOI： 10.1016/j.yexcr.2004.03.023
Sequential interaction of actin-related proteins 2 and 3 (Arp2/3) complex with neural Wiscott-Aldrich syndrome protein (N-WASP) and cortactin during branched actin filament network formation. Reviewed

Takehito Uruno

The Journal of biological chemistry 2003.5

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Authorship：Lead author Language：Others Publishing type：Research paper (scientific journal)

DOI： 10.1074/jbc.m301997200, 10.1074/jbc.M301997200
Haematopoietic lineage cell-specific protein 1 (HS1) promotes actin-related protein (Arp) 2/3 complex-mediated actin polymerization. Reviewed

Takehito Uruno

The Biochemical journal 2003.4

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Authorship：Lead author Language：Others Publishing type：Research paper (scientific journal)

DOI： 10.1042/BJ20021791
Osmotic stress-induced remodeling of the cortical cytoskeleton. Reviewed

Takehito Uruno

American journal of physiology. Cell physiology 2002.9

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DOI： 10.1152/ajpcell.00018.2002
Fibroblast growth factor-1 interacts with the glucose-regulated protein GRP75/mortalin. Reviewed

Takehito Uruno

The Biochemical journal 1999.10

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DOI： 10.1042/bj3430461
Distinct regulation of myoblast differentiation by intracellular and extracellular fibroblast growth factor-1. Reviewed

Takehito Uruno

Growth factors (Chur, Switzerland) 1999.1

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DOI： 10.3109/08977199909103519
The C-terminal region of fibroblast growth factor-1 is crucial for its biological activity and high level protein expression in mammalian cells. Reviewed

Takehito Uruno

Growth factors (Chur, Switzerland) 1999.1

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DOI： 10.3109/08977199909002129
Expression of the fibroblast growth factor family and their receptor family genes during mouse brain development. Reviewed

Takehito Uruno

Brain research. Molecular brain research 1996.9

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DOI： 10.1016/0169-328x(96)00108-8, 10.1016/0169-328X(96)00108-8

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Presentations

A tumor metabolite impacting immunotherapy efficacy: Cholesterol sulfate regulates tumor-immune interactions Invited International conference

Takehito Uruo, Takaaki Tatsuguchi, Yuki Sugiura, Yoshinori Fukui

Keystone Symposia on "Cancer Immunotherapy: Mechanisms of Response versus Resistance" 2023.3

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Event date： 2023.3

Language：English Presentation type：Symposium, workshop panel (public)

Country：Japan
コレステロール代謝と疾患制御の新たな展開

宇留野武人（オーガナイザー）、大石由美子（オーガナイザー）講演者リスト：佐藤隆一郎（東京大学大学院農学生命科学研究科) Esperanza Perucha（Centre for Inflammation Biology and Cancer Immunology;Centre for Rheumatic Diseases, King’s College London) 高橋勇人（慶應義塾大学医学部) 大石由美子（日本医科大学大学院医学研究科) 小黒秀行（University of Connecticut Health Center) 國村和史（九州大学生体防御医学研究所) 宇留野武人（九州大学生体防御医学研究所）

第95回日本生化学大会 2022.11

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Event date： 2022.11

Language：Japanese Presentation type：Symposium, workshop panel (public)

Venue：名古屋国際会議場 Country：Japan

コレステロールは、細胞膜の主要構成成分の一つであると共に、各種ステロイドホルモン生合成の起点となり、生命活動の維持に不可欠の役割を果たす。社会の長寿高齢化が進む中で、コレステロールと生活習慣病や慢性疾患の関係に大きな関心が寄せられているが、依然として不明な点が多く残されている。最近、その代謝過程で生じる様々なコレステロール代謝産物が、免疫応答やがん、炎症制御において重要な役割を担うことが次々と明らかにされ、トランスレーショナル・リサーチの観点からも大きな注目を集めている。そこで、本シンポジウムでは、これら最新の知見を紹介し、コレステロール代謝と生体機能・疾患制御の関係性を新たな視点から俯瞰することで、コレステロール・バイオロジーの更なる進化と発展を促す機会としたい。
ホスファチジン酸産生酵素PLD1は好中球細胞外トラップの形成に必須である

@宇留野武人、@相原良亮

第101回日本生理学会大会 2024.3

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Event date： 2024.3

Language：Japanese Presentation type：Oral presentation (general)

Venue：福岡県北九州市小倉 Country：Japan
がん免疫療法に対する抵抗性を付与する腫瘍メタボライト

@宇留野　武人、#竜口　崇明、@杉浦　悠毅、@福井宣規

第27回日本がん免疫学会総会 2023.7

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Event date： 2023.7

Language：Japanese Presentation type：Oral presentation (general)

Venue：三重県津市 Country：Japan
マウスハーダー腺の加齢に伴うトランスクリプトーム・リピドーム変化

宇留野武人、高橋政友

日本生理学会第100回記念大会 2023.3

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Event date： 2023.3

Language：Japanese

Venue：国立京都国際会館 Country：Japan
A tumor metabolite impacting immunotherapy efficacy: Cholesterol sulfate regulates tumor-immune interactions Invited

Takehito Uruno, Takaaki Tatsuguchi, Yuki Sugiura, Yoshinori Fukui

Keystone Symposia "Cancer Immunotherapy: Mechanisms of Response versus Resistance" 2023.3

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Event date： 2023.3

Language：Others

Country：Other
A tumor metabolite impacting immunotherapy efficacy: Cholesterol sulfate regulates tumor-immune interactions Invited

Takehito Uruno, Takaaki Tatsuguchi, Yuki Sugiura, Yoshinori Fukui

Keystone Symposia "Cancer Immunotherapy: Mechanisms of Response versus Resistance" 2023.3

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Event date： 2023.3

Presentation type：Oral presentation (invited, special)

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RAS変異を有する難治性がんの新規分子標的治療薬の開発

宇留野武人、坂田大治、福井宣規、生長幸之助

第94回日本生化学会大会 2021.11

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Event date： 2021.11 - 2022.6

Language：Japanese Presentation type：Oral presentation (general)

Venue：京都 Country：Japan
DOCK1 as a novel molecular target for controlling cancer cell survival and invasion International conference

Tatsuguchi T, Uruno T, Fukui Y

25th Biennial Congress on the European Association for Cancer Research 2018.7

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Event date： 2018.7

Language：English

Country：Netherlands
細胞骨格制御とシグナル伝達におけるDOCKファミリー分子の多彩な機能と構造基盤～DOCK GEF発見から20年を経て～　DOCK2/DOCK8分子を介した多彩な免疫制御メカニズム

國村和史, 宇留野武人, 福井宣規

日本生化学会大会プログラム・講演要旨集 2023.10 (公社)日本生化学会

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Language：Japanese
マウスハーダー腺の加齢に伴うトランスクリプトーム・リピドーム変化(Transcriptome and lipidome analyses of mouse Harderian glands in aging)

Uruno Takehito, Takahashi Masatomo

The Journal of Physiological Sciences 2023.5 (一社)日本生理学会

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Language：English
コレステロール関連代謝産物と疾患制御　コレステロール硫酸を介した腫瘍の免疫回避と創薬応用

宇留野武人

日本生化学会大会プログラム・講演要旨集 2022.11 (公社)日本生化学会

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Language：Japanese
コレステロール関連代謝産物と疾患制御　コレステロール硫酸は白血球の遊走制御を介して眼の免疫特権環境の形成に寄与する

國村和史, 宇留野武人, 杉浦悠毅, 福井宣規

日本生化学会大会プログラム・講演要旨集 2022.11 (公社)日本生化学会

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Language：Japanese
がん免疫療法に対する抵抗性を付与する腫瘍メタボライト

宇留野武人, 竜口崇明, 杉浦悠毅, 福井宣規

日本がん免疫学会総会プログラム・抄録集 2023.6 日本がん免疫学会

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Language：Japanese
PLD1欠損がNeutrophil extracellular traps(NETs)産生に及ぼす影響

相原良亮, 宇留野武人, 北村知昭

特定非営利活動法人日本歯科保存学会学術大会プログラムおよび講演抄録集 2024.4 (NPO)日本歯科保存学会

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Language：Japanese
Phospholipase D1は好中球細胞外トラップの形成に必須である(Phospholipase D1 is essential for neutrophil extracellular trap formation)

Uruno Takehito, Aihara Ryosuke

The Journal of Physiological Sciences 2024.5 (一社)日本生理学会

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Language：English
Phospholipase D1は好中球細胞外トラップの形成に必須である(Phospholipase D1 is essential for neutrophil extracellular trap formation)

Uruno Takehito, Aihara Ryosuke

The Journal of Physiological Sciences 2024.5 (一社)日本生理学会

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Language：English
Phospholipase D1は好中球細胞外トラップの形成に必須である(Phospholipase D1 is essential for neutrophil extracellular trap formation)

Uruno Takehito, Aihara Ryosuke

The Journal of Physiological Sciences 2024.5 (一社)日本生理学会

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Language：English

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MISC

DOCK-family proteins: key players in immune surveillance mechanisms Reviewed

Takehito Uruno

International Immunology 2019.10

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Language：English

DOI： 10.1093/intimm/dxz067

Professional Memberships

日本がん免疫学会

2023.4 - Present

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日本生理学会

2020.2 - Present

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The Japanese Biochemical Society

- Present

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The Japanese Biochemical Society
日本生理学会
日本がん免疫学会
日本がん免疫学会

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Academic Activities

Screening of academic papers

Role(s)： Peer review

2023

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Type：Peer review

Number of peer-reviewed articles in foreign language journals：2
事前準備、運営全般 International contribution

（九州大学病院キャンパス） 2014.11

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Type：Competition, symposium, etc.

Number of participants：300

Research Projects

令和5年度鈴木謙三記念医科学応用研究財団研究助成

2024

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Grant type：Donation
基盤研究(B) 腫瘍の免疫特権環境形成における硫酸化コレステロールの役割と創薬応用

2021.4 - 2024.3

九州大学（日本）

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Authorship：Principal investigator

腫瘍の免疫特権環境形成における硫酸化コレステロールの役割と創薬応用、機能生物化学関連分野
AMED革新的がん医療実用化研究事業、「RAS変異を有する難治性がんの新規分子標的治療薬の非臨床評価」

2019.7 - 2022.3

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Authorship：Principal investigator
RAS変異を有する難治性がんの新規分子標的治療薬の非臨床評価

2019 - 2021

AMED 革新的がん医療実用化研究事業

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Authorship：Principal investigator Grant type：Contract research
基盤研究(B) 腫瘍の免疫回避機構におけるRac活性化因子DOCK1の機能

2018.4 - 2021.3

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Authorship：Principal investigator
リジン水酸化酵素Jmjd6を介したAire発現制御の分子基盤とその進化学的考察

2016.4 - 2019.3

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Authorship：Coinvestigator(s)
革新的先端研究開発支援事業インキュベートタイプ（LEAP） DOCKファミリー分子の生体機能と動作原理の理解に基づく革新的医薬品の創出

2015.11 - 2020.3

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Authorship：Coinvestigator(s)
基盤研究(C)　ヒト変異型Racによる細胞癌化におけるDOCKファミリー分子の役割

2014.4 - 2017.3

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Authorship：Principal investigator
創薬等支援技術基盤プラットフォーム事業「大型創薬研究基盤を活用した創薬オープンイノベーションの推進（九州大学拠点推進事業）」

2014.4 - 2016.3

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Authorship：Coinvestigator(s)
次世代がん研究戦略推進プロジェクト

2014.4 - 2015.3

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Authorship：Coinvestigator(s)
橋渡し研究・新規開発シーズA

2014.4 - 2015.3

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Authorship：Collaborating Investigator(s) (not designated on Grant-in-Aid)
基盤研究（A)　DOCKファミリー分子の生体機能と動作原理の統合的理解

2014.1 - 2016.3

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Authorship：Coinvestigator(s)
硫酸基転移酵素SULT2B1bの発現制御機構と生体機能の統合的理解

Grant number：19H00983

福井宣規, 宇留野武人

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Grant type：Scientific research funding

研究代表者は、SULT2B1bによって生成されるコレステロール硫酸（CS）が、免疫細胞の遊走や活性化に重要なRac活性化因子であるDOCK2の触媒ドメインに会合し、その機能を阻害することを見出した。本研究では、SULT2B1bの遺伝子発現制御機構を解明し、その発現を個体レベルでモニターできるレポーターマウスを開発すると共に、妊娠時の胎盤や子宮、がん組織等を対象に、SULT2B1bを介したCS産生の免疫回避における機能的重要性を実証する。

CiNii Research

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Class subject

免疫学

2023.4 - 2023.9 First semester
医学研究特論 I

2023.4 - 2023.9 First semester
医学研究特論 I

2021.10 - 2022.3 Second semester

FD Participation

2019.10 Role：Panelist Title：馬出地区4部局合同男女共同参画ＦＤ

Organizer：[Undergraduate school/graduate school/graduate faculty]
2017.10 Role：Participation Title：「無意識のバイアスからの開放：ダイバーシティのススメ」

Organizer：University-wide
2016.10 Role：Participation Title：「なぜ今『女性活躍推進法』か？　　　—男女共同参画の必要性と九州大学における取組み—」

Organizer：University-wide

Other educational activity and Special note

2023 Class Teacher
2021 Special Affairs
2017 Special Affairs

Media Coverage

がん抑える新化合物九大など、副作用少ない薬開発に期待 TV or radio program

2017.5

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がん抑える新化合物九大など、副作用少ない薬開発に期待
九州大・研究グループがん抑える新たな化合物を開発 Newspaper, magazine

2017.5

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九州大・研究グループがん抑える新たな化合物を開発