生体機能解析学分野

研究概要

   本分野では、内分泌代謝疾患や代謝性骨疾患ならびに腎疾患における病態解明や新規治療標的となる分子に焦点を当てて研究を展開している。具体的には遺伝子改変マウスモデルの解析および臨床研究を融合し、1) 代謝性骨疾患における病態の解明と新規治療法の開発、2) メタボリック症候群/糖尿病と骨粗鬆症の連関、3) 骨脆弱性をきたすホルモンおよびCa/P代謝異常、4)腎疾患における病態の解明と新規治療法の開発について検討を進めている。

 

   Our department focuses on the areas of endocrine disorders, metabolic bone diseases     and nephropathy. Our research goal is elucidation of the molecular mechanisms of these disorders as well as development of molecular-targeted therapy against these diseasesby using  translational and clinical research methods.  We have the following research project. 1) Analysis molecular mechanisms and development of newly therapeutic methods for metabolic bone diseases. 2) Elucidation of the pathological interplay between metabolic syndrome/diabetes mellitus and osteoporosis. 3) Clarification of the pathophysiology of bone fragility depends on dysfunction of endocrine system and/or abnormal calcium/phosphate metabolism. 4)Analysis molecular mechanisms and development of newly therapeutic methods for nephropathy.

 

 

主要研究テーマ 

① 代謝性骨疾患の病態解明と治療ターゲットの同定

骨カルシウム代謝異常症とメタボリック症候群・糖代謝の連関解明

内分泌代謝・腎疾患における新規バイオマーカーの検索

 

メンバー 

教授 遠藤逸朗(ENDO Itsuro MD,PhD

准教授 冨永辰也(TOMINAGA Tatsuya PhD

 

所属学生 

<大学院生>

博士課程後期(R1年度入学):金井麻衣

<学部生>

毎年6-7名程度募集

 

発表論文(2017年以降)

  1. Matsumoto T, Endo I: Minodronate. BONE. 2020 15th May online available.

  2. Ashtar M, Tenshin H, Teramachi J, Bat-Erdene A, Hiasa M, Oda A, Tanimoto K, Shimizu S, Higa Y, Harada T, Oura M, Sogabe K, Nakamura S, Fujii S, Sumitani R, Miki H, Udaka K, Takahashi M, Kagawa K, Endo I, Tanaka E, Matsumoto T, Abe M.: The Roles of ROS Generation in RANKL-Induced Osteoclastogenesis: Suppressive Effects of Febuxostat.Cancers (Basel). 2020 Apr 9;12(4). pii: E929. doi: 10.3390/cancers12040929.

  3. Teramachi J, Tenshin H, Hiasa M, Oda A, Bat-Erdene A, Harada T, Nakamura S, Ashtar M, Shimizu S, Iwasa M, Sogabe K, Oura M, Fujii S, Kagawa K, Miki H, Endo I, Haneji T, Matsumoto T, Abe M.: TAK1 is a pivotal therapeutic target for tumor progression and bone destruction in myeloma.Haematologica. 2020 Apr 9. pii: haematol.2019.234476. doi: 10.3324/haematol.2019.234476.

  4. Yumi Kuwamura, Sumiko Yoshida, Kiyoe Kurahashi, Masuko Sumikawa, Eijiro Sakamoto, Ken-ichi Aihara, Hiromichi Yumoto, Akio Kuroda, Itsuro Endo, Toshiyuki Yasui and Sachi Kishida : Modified diabetesoral health assessment tool (M-DiOHAT©) for nurses and their association with efficacy beliefs and outcome expectancies in patients with diabetes, JNI : The Journal of Nursing Investigation, Vol.17, No.2, (in press), 2020.

  5. Yagi S, Endo I, Murakami T, Hida T, Yamamoto Y, Soga T, Ise T, Kusunose K, Yamaguchi K, Fukuda D, Yamada H, Soeki T, Wakatsuki T, Kawahito S, Sata M.: Adult onset of Immunoglobulin A vasculitis - A case report. J Med Invest. 2019;66(3.4):344-346. doi: 10.2152/jmi.66.344.

  6. Mori H, Kuroda A, Ishizu M, Ohishi M, Takashi Y, Otsuka Y, Taniguchi S, Tamaki M, Kurahashi K, Yoshida S, Endo I, Aihara KI, Funaki M, Akehi Y, Matsuhisa M.: Association of accumulated advanced glycation end-products with a high prevalence of sarcopenia and dynapenia in patients with type 2 diabetes. J Diabetes Investig. 2019 Sep;10(5):1332-1340. doi: 10.1111/jdi.13014.

  7. Miki H, Nakamura S, Oura M, Hamano H, Ikuta K, Okada N, Okamoto Y, Sogabe K, Takahashi M, Iwasa M, Udaka K, Harada T, Kurahashi K, Fujii S, Yoshida S, Kagawa K, Endo I, Aihara K, Abe M. Correlation between high serum alkaline phosphatase levels and denosumab-related hypocalcemia in patients with multiple myeloma. Br J Haematol. 2019 Jul;186(2):355-358. doi: 10.1111/bjh.15837.

  8. Bat-Erdene A, Nakamura S, Oda A, Iwasa M, Teramachi J, Ashtar M, Harada T, Miki H, Tenshin H, Hiasa M, Fujii S, Sogabe K, Oura M, Udaka K, Kagawa K, Yoshida S, Aihara K, Kurahashi K, Endo I, Abe M. Class 1 HDAC and HDAC6 inhibition inversely regulates CD38 induction in myeloma cells via interferon-a and ATRA. Br J Haematol. 2019 185(5):969-974. doi: 10.1111/bjh.15673.

  9. Bingzi Dong, Itsuro Endo, Yukiyo Ohnishi, Yukari Mitsui, Kiyoe Kurahashi, Mai Kanai, Masahiro Hiasa, Jumpei Teramachi, Hirofumi Tenshin, Seiji Fukumoto, Masahiro Abe, Toshio Matsumoto, Persistent activation of calcium-sensing receptor suppresses bone turnover, increases microcracks and decreases bone strength. JBMR plus 2019 Mar 6;3(7):e10182. doi: 10.1002/jbm4.10182.

  10. Masanori Tamaki, Tatsuya Tominaga, Yui Fujita, Yasuhiko Koezuka, Go Ichien, Taichi Murakami, Seiji Kishi, Keiichi Yamamoto, Hideharu Abe, Kojiro Nagai and Toshio Doi : All-trans retinoic acid suppresses bone morphogenetic protein 4 in mouse diabetic nephropathy through a unique retinoic acid response element., American Journal of Physiology, Endocrinology and Metabolism, Vol.316, No.3, E418-E431, 2019.

  11. Teramachi J, Hiasa M, Oda A, Harada T, Nakamura S, Amachi R, Tenshin H, Iwasa M, Fujii S, Kagawa K, Miki H, Kurahashi K, Yoshida S, Endo I, Haneji T, Matsumoto T, Abe M. Pim-2 is a critical target for treatment of osteoclastogenesis enhanced in myeloma.Br J Haematol. 2018;180(4):581-585.

  12. Yagi S, Aihara K, Kondo T, Kurahashi K, Yoshida S, Endo I, Fukuda D, Nakaya Y, Suwaki K, Takeji T, Wada T, Salim HM, Hama S, Matsuura T, Ise T, Kusunose K, Yamaguchi K, Tobiume T, Yamada H, Soeki T, Wakatsuki T, Matsuhisa M, Shimabukuro M, Akaike M, Sata M. Predictors for the treatment effect of sodium glucose co-transporter 2 inhibitors in patients with type 2 diabetes mellitus. Adv Ther. 2018 Jan;35(1):124-134.

  13. Fujii S, Nakamura S, Oda A, Miki H, Tenshin H, Teramachi J, Hiasa M, Bat-Erdene A, Maeda Y, Oura M, Takahashi M, Iwasa M, Endo I, Yoshida S, Aihara KI, Kurahashi K, Harada T, Kagawa K, Nakao M, Sano S, Abe M.:Unique anti-myeloma activity by thiazolidine-2,4-dione compounds with Pim inhibiting activity.Br J Haematol. 2018 Jan;180(2):246-258.

  14. Tatsuya Tominaga, Isha Sharma, Yui Fujita, Toshio Doi, K Aryana Wallner and S Yashpal Kanwar: Myo-inositol oxygenase accentuates renal tubular injury initiated by endoplasmic reticulum stress.,
    American Journal of Physiology, Renal PhysiologyVol.316, No.2, F301-F315, 2018.

  15. Yui Fujita, Tatsuya Tominaga, Hideharu Abe, Yumi Kangawa, Naoshi Fukushima, Otoya Ueda, Kou-Ichi Jishage, Seiji Kishi, Taichi Murakami, Yumiko Saga, S Yashpal Kanwar, Kojiro Nagai and Toshio Doi: An adjustment in BMP4 function represents a treatment for diabetic nephropathy and podocyte injury., Scientific Reports, Vol.8, No.1, 2018.

  16. Hiroyuki Ono, Hideharu Abe, Akiko Sakurai, Arisa Ochi, Tatsuya Tominaga, Masanori Tamaki, Seiji Kishi, Taichi Murakami, Kojiro Nagai, Masayuki Kohashi and Toshio Doi: Novel Interplay Between Smad1 and Smad3 Phosphorylation via AGE Regulates the Progression of Diabetic Nephropathy., Scientific Reports, Vol.8, No.1, 2018.

  17. Fumi Kishi, Kojiro Nagai, Norimichi Takamatsu, Tatsuya Tominaga, Masanori Tamaki, E. Shibata, Taichi Murakami, Seiji Kishi, Hideharu Abe, Y Koezuka, N Minagawa, G Ichien and Toshio Doi: Urinary type IV collagen excretion is involved in the decline in estimated glomerular filtration rate in the Japanese general population without diabetes: A 5-year observational study., PLoS ONE, Vol.13, No.4, e0195523, 2018.

  18. Toshio Doi, Hideharu Abe, Seiji Kishi, Taichi Murakami, Kojiro Nagai and Tatsuya Tominaga: Urinary IgG4 and Smad1 are Specific Biomarkers for Renal Structural and Functional Changes in Early Stages of Diabetic Nephropathy., Diabetes, Vol.67, No.5, 986-993, 2018.

  19. Hideharu Abe and Tatsuya Tominaga: New insights into the molecular pathology and the development of predictive biomarkers in diabetic mephropathy., Trends in Cell & Molecular Biology, Vol.13, No.4, 19-26, 2018.

  20. Miki H, Nakamura S, Oda A, Tenshin H, Teramachi J, Hiasa M, Bat-Erdene A, Maeda Y, Oura M, Takahashi M, Iwasa M, Harada T, Fujii S, Kurahashi K, Yoshida S, Kagawa K, Endo I, Aihara K, Ikuo M, Itoh K, Hayashi K, Nakamura M, Abe M.:Effective impairment of myeloma cells and their progenitors by hyperthermia.Oncotarget. 2017 Dec 7;9(12):10307-10316.

  21. Tenshin H, Teramachi J, Oda A, Amachi R, Hiasa M, Bat-Erdene A, Watanabe K, Iwasa M, Harada T, Fujii S, Kagawa K, Sogabe K, Nakamura S, Miki H, Kurahashi K, Yoshida S, Aihara K, Endo I, Tanaka E, Matsumoto T, Abe M.: TAK1 inhibition subverts the osteoclastogenic action of TRAIL while potentiating its antimyeloma effects.Blood Adv.2017 Oct 26;1(24):2124-2137.

  22. Okazaki J, Muguruma N, Kitamura N, Kimura T, Okamoto K, Miyamoto H, Kishi K, Bando Y, Kondo T, Endo I, Abe M, Takayama T.: Paraneoplastic hypocalcemia developed in gastric cancer accompanied by osteoblastic metastasis Inter Med 2017;56(11):1345-1349.

  23. Kurahashi K, Endo I, Kondo T, Morimoto K, Yoshida S, Kuroda A, Aihara KI, Matsuhisa M, Nakajima K, Mizobuchi Y, Nagahiro S, Abe M, Fukumoto S.: Remarkable Shrinkage of a Growth Hormone (GH)-secreting Macroadenoma Induced by Somatostatin Analogue Administration: A Case Report and Literature Review. Intern Med. 2017 Sep 15;56(18):2455-2461.

  24. Kurahashi K, Inoue S, Yoshida S, Ikeda Y, Morimoto K, Uemoto R, Ishikawa K, Kondo T, Yuasa T, Endo I, Miyake M, Oyadomari S, Matsumoto T, Abe M, Sakaue H, Aihara KI.: The Role of Heparin Cofactor Ⅱ in the Regulation of Insulin Sensitivity and Maintenance of Glucose Homeostasis in Humans and Mice. J Atheroscler Thromb. 2017 May 15. doi: 10.5551/jat.37739.

  25. Yoshimoto S, Nagai K, Shibata E, Ueda S, Ono H, Tamaki M, Nishimura K, Obata F, Inagaki T, Minato M,Kishi F, Matsuura M, Matsui N, Endo I, Hann M, Kishi S, Murakami T, Abe H, Doi T: Influential factors on serum albumin concentration in hospitalized chronic kidney disease patients J Med Invest:64(1,2); 146-152, 2017.

  26. Harada T, Miki H, Cui Q, Oda A, Amachi R, Teramachi J, Bat-Erdene A, Sogabe K, Iwasa M, Fujii S, Nakamura S, Kagawa K, Yoshida S, Endo I, Aihara K, Ozaki S, Matsumoto T, Abe M.: Expansion of Th1-like Vγ92T cells by new-generation IMiDs, lenalidomide and pomalidomide, in combination with zoledronic acid.Leukemia. 2017 Jan;31(1):258-262.

  27. Kojiro Nagai, Tatsuya Tominaga, Sayo Ueda, Eriko Shibata, Masanori Tamaki, Motokazu Matsuura, Seiji Kishi, Taichi Murakami, Tatsumi Moriya, Hideharu Abe and Toshio Doi: Mesangial Cell Mammalian Target of Rapamycin Complex 1 Activation Results in Mesangial Expansion., Journal of the American Society of Nephrology, Vol.28, No.10, 2879-2885, 2017.

  28. Motokazu Matsuura, Hideharu Abe, Tatsuya Tominaga, Akiko Sakurai, Taichi Murakami, Seiji Kishi, Yoshimi Bando, Jun Minakuchi, Kojiro Nagai and Toshio Doi: A Novel Method of DAPI Staining for Differential Diagnosis of Renal Amyloidosis., The Journal of Medical Investigation : JMI, Vol.64, No.3.4, 217-221, 2017.