G protein-coupled receptors and diseases: signal crosstalk and therapeutics
Project/Area Number |
16K09813
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Endocrinology
|
Research Institution | St. Marianna University School of Medicine |
Principal Investigator |
Iiri Taroh 聖マリアンナ医科大学, 医学部, 教授 (90313022)
|
Research Collaborator |
MAKITA noriko
SATO Junichiro
MANAKA katsunori
MITANI koji
OOTAKI masanori
TAKEBA yuko
OHTA yuki
WATANABE minoru
MATSUMOTO naoki
OHWADA tomohiko
|
Project Period (FY) |
2016-10-21 – 2019-03-31
|
Project Status |
Completed (Fiscal Year 2018)
|
Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | 内分泌学 / Gタンパク質共役受容体 / GPCR / クロストーク / 疾患解析制御 / バイアスアゴニズム |
Outline of Final Research Achievements |
G protein-coupled receptors (GPCRs) and their crosstalks may play an important role in fine-tuning of many signals in our body, and their signal unbalance may underlie many disease states. In this study, 1) we have screened and analyzed molecular defects of GPCRs in diseases and tried to rescue them using small molecules targeting GPCRs in vitro and also in patients. 2) We have also designed analogues of small molecules that nitrosyl ate and thereby inactivate GRK2 (G protein-coupled receptor kinase 2 that plays an essential role in many GPCR desensitization) and analyzed their effects on lipolysis of adipocytes. 3)We have also analyzed molecular action of GPCRs by combining accumulated data based on G protein/GPCR disease analysis and structural information.
|
Academic Significance and Societal Importance of the Research Achievements |
GPCRとそのクロストークの分子異常に基づく疾患の解析と小分子化合物による制御、in silicoを含めた制御ツール開発は、疾患メカニズム解明とともにGPCR研究における普遍的示唆を与えることが期待され、さらには新たな創薬へと結実することが期待される。
|
Report
(4 results)
Research Products
(47 results)
-
-
[Journal Article] Cinacalcet corrects biased allosteric modulation of CaSR by AHH autoantibody2019
Author(s)
Noriko Makita, Takao Ando, Junichiro Sato, Katsunori Manaka, Koji Mitani, Yasuko Kikuchi, Takayoshi Niwa, Masanori Ootaki, Yuko Takeba,4 Naoki Matsumoto, Atsushi Kawakami, Toshihisa Ogawa, Masaomi Nangaku, and Taroh Iiri
-
Journal Title
JCI Insight
Volume: in press
Issue: 8
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
[Journal Article] Molecular analysis and literature-based hypothesis of an immunonegative prostate small cell carcinoma causing ectopic ACTH syndrome2019
Author(s)
Takeuchi M, Sato J, Manaka K, Tanaka M, Matsui H, Sato Y, Kume H, Fukayama M, Iiri T, Nangaku M, Makita N
-
Journal Title
Endocrine Journal
Volume: 66
Issue: 6
Pages: 547-554
DOI
NAID
ISSN
0918-8959, 1348-4540
Related Report
Peer Reviewed / Open Access
-
-
-
-
[Journal Article] <b>Population Profile of Cytochrome P450 Isozymes in the Small Intestine of Japanese </b>2018
Author(s)
Takenoshita-Nakaya Sachiko,Takeba Yuko, Ohta Yuki, Ootaki Masanori, Watanabe Minoru, Iiri Taroh, Otsubo Takehito, Kobayashi Tsukasa, Machida Takafumi, Watanabe Daiki, Nakamura Yuki, Yamamoto Makoto, Kumai Toshio, Kobayashi Shinichi, Matsumoto Naoki
-
Journal Title
Rinsho yakuri/Japanese Journal of Clinical Pharmacology and Therapeutics
Volume: 49
Issue: 1
Pages: 3-6
DOI
NAID
ISSN
0388-1601, 1882-8272
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
[Presentation] Molecular dynamics studies of the pH-dependent dynamic structure of VYP2D62018
Author(s)
Masanori Ootaki, Yuki Ohta, Minoru Watanabe, Tsukasa Kobayashi, Yuki Nakamura, Daiki Watanabe, Makoto Yamamoto, Yuko Takeba, Taroh Iiri, Naoki Matsumoto
Organizer
WCP2018 KYOTO, 18th WORLD CONGRESS OF BASIC AND CLINICAL PHARMACOLOGY
Related Report
Int'l Joint Research
-
-
[Presentation] Monitoring of Rivaroxaban in patients with atrial fibrillation2018
Author(s)
Yuki Ohta, Makoto Takano, Tsukasa Kobayashi, Yuko Takeba, Masanori Ootaki, Minoru Watanabe, Yuki Nakamura, Taroh Iiri, Yoshihiro Akashi, Naoki Matsumoto
Organizer
WCP2018 KYOTO, 18th WORLD CONGRESS OF BASIC AND CLINICAL PHARMACOLOGY
Related Report
Int'l Joint Research
-
[Presentation] Introduction of a cartilage calcification insufficient rat as infertile model animal2018
Author(s)
Minoru Watanabe, Masami Tanaka, Yuko Takeba, Masanori Ootaki, Yuki Ohta, Taroh Iiri, Tsukasa Kobayashi, Daiki Watanabe, Toshio Kumai, Naoki Matsumoto
Organizer
WCP2018 KYOTO, 18th WORLD CONGRESS OF BASIC AND CLINICAL PHARMACOLOGY
Related Report
Int'l Joint Research
-
-
-
-
-
-
[Presentation] Analysis of the V2 vasopressin receptor (V2R) mutations causing partial nephrogenic diabetes insidious highlights a sustainable signaling by an non-peptide V2R agonist.2017
Author(s)
Makita N, Sato T, Yajima-Shoji Y, Sato J, Manaka K, Eda-Hashimoto, M, Ootaki M, Matsumoto N, Nangaku M and Iiri T.
Organizer
Gordon Research Conference
Place of Presentation
Renaissance Tuscany Il Ciocco(Lucca (Barga), Italy)
Year and Date
2017-03-12
Related Report
-
-
-
-
-
-
-
-
-
-
-
-
-
[Presentation] ヒト乳癌細胞に対する新規KSP(kinesin spindle protein)阻害薬の効果.2016
Author(s)
太田有紀, 土屋聖子, 武永美津子, 角田智志, 大滝正訓, 新美純, 大石真也, 藤井信孝, 渡辺実, 武半優子, 飯利太朗 , 松本直樹.
Organizer
第37回日本臨床薬理学会
Place of Presentation
米子コンベンションセンター(鳥取県・米子市)
Year and Date
2016-12-01
Related Report
-
[Presentation] 自然発症不妊症ラッ トの不妊機序の解明.2016
Author(s)
渡辺実, 田中政巳, 武半優子, 太田有紀, 大滝正訓, 飯利太朗, 渡邉大輝, 熊井俊夫, 松本直樹.
Organizer
第37回日本臨床薬理学会学術総会
Place of Presentation
米子コンベンションセンター(鳥取県・米子市)
Year and Date
2016-12-01
Related Report
-
-
-
-