PRINCIPAL INVESTIGATOR
Takeshi Inagaki, M.D, Ph.D.
Takeshi Inagaki, M.D., Ph.D., is Professor at the Institute of Molecular and Cellular Regulation, Gunma University. His research focuses on the mechanisms by which metabolic and environmental signals regulate gene expression through nuclear receptors, histone modifiers, and chromatin remodeling complexes. His recent work explores how iron acts as a metabolic signal in epigenomic regulation and how epigenetic memory is dynamically shaped in response to cellular environments—insights with implications for metabolic diseases such as obesity, diabetes, and fatty liver disease.
After graduating from the Faculty of Medicine at Shinshu University in 1999, Inagaki began his research career while practicing internal medicine. His early studies focused on retinoic acid receptors (RARs)—nuclear receptors for vitamin A—and led to the successful cloning and functional analysis of an RAR-responsive gene, APBB1IP.
From 2002 to 2008, he worked in the laboratories of Professors Steven Kliewer and David Mangelsdorf at the University of Texas Southwestern Medical Center, first as a research fellow and later as an instructor. There, he investigated how nuclear receptors mediate metabolic adaptation to fasting and feeding, leading to the discovery of the PPARα–FGF21 and FXR–FGF15 axes, which contributed to the conceptualization of the “nuclear receptor–endocrine FGF axis.”
From 2008 to 2016, Inagaki conducted research in the Division of Metabolic Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, in the laboratory of Professor Juro Sakai. During this time, he investigated how chromatin architecture interacts with nuclear receptor complexes to regulate transcription. He contributed to discoveries revealing that mice lacking the histone demethylase JMJD1A display features of metabolic syndrome and that serine 265 (S265) of JMJD1A is phosphorylated via β-adrenergic signaling. This phosphorylation leads to the formation of the JMJD1A–SWI/SNF–PPARγ complex, which mediates chromatin looping and enhancer-promoter interaction to control gene expression.
He later identified FBXL10, another histone demethylase, as a factor involved in similar epigenetic mechanisms. These findings led to a broader concept in which histone demethylases serve as environmental signal sensors, dynamically coordinating chromatin structure and transcriptional responses to metabolic cues.
・Mechanisms of metabolic regulation
・Epigenetics
・Transcriptional regulation via histone modifications and chromatin structure
・Nuclear receptors and endocrine FGFs
・Iron metabolism and epigenomic regulation
Crucial role of iron in epigenetic rewriting during adipocyte differentiation mediated by JMJD1A and TET2 activity.
Suzuki T., Komatsu T., Shibata H., Tanioka A., Vargas D., Kawabata-Iwakawa R., Miura F., Masuda S., Hayashi M., Tanimura-Inagaki K., Morita S., Kohmaru J., Adachi K., Tobo M., Obinata H., Hirayama T., Kimura H., Sakai J., Nagasawa H., Itabashi H., Hatada I., Ito T., Inagaki T.* (2023).
Nucleic Acids Res.51(12):6120-6142. PMID: 37158274 (*Corresponding author)
Histone demethylase JMJD1A coordinates acute and chronic adaptation to cold stress via thermogenic phospho-switch
Abe Y., Fujiwara Y., Takahashi h., Matsumura Y., Sawada T., Jiang S., Nakaki R., Uchida A., Nagao N., Naito M., Kajimura S., Kimura H., Osborne T.F., Aburatani H., Kodama T., Inagaki T.*, Sakai J.* (2018)
Nature Communications 19;9(1):1566. PMID: 29674659 (*Corresponding author)
Transcriptional and epigenetic control of brown and beige adipocyte cell fate and function.
Inagaki T., Sakai J, Kajimura S. (2016)
Nature Reviews Molecular Cell Biology 17(8):480-95. Review. PMID: 27251423
JMJD1A is a signal-sensing scaffold that regulates acute chromatin dynamics via SWI/SNF association for thermogenesis.
Abe Y., Rozqie R., Matsumura Y., Kawamura T., Nakaki R., Tsurutani Y., Tanimura-Inagaki K., Shiono A., Magoori K., Nakamura K., Ogi S., Kajimura S., Kimura H., Tanaka T., Fukami K., Osborne T.F., Kodama T., Aburatani H., Inagaki T.*, Sakai J.* (2015)
Nature Communications 7;6:7052. PMID: 25948511 (*Corresponding author)
The FBXL10/KDM2B scaffolding protein associates with novel polycomb repressive complex-1 to regulate adipogenesis.
Inagaki T.*, Iwasaki S., Matsumura Y., Kawamura T., Tanaka T., Abe Y., Yamasaki A., Tsurutani Y., Yoshida A., Chikaoka Y., Nakamura K., Magoori K., Nakaki R., Osborne T.F., Fukami K., Aburatani H., Kodama T., Sakai J.* (2015).
J. Biol. Chem. 290(7):4163-77. PMID: 25533466 (*Corresponding author)
Obesity and Metabolic Syndrome in Histone Demethylase JHDM2a Deficient Mice.
Inagaki T., Tachibana M., Magoori K., Kudo H., Tanaka T., Okamura M., Naito M., Kodama T., Shinkai Y., Sakai J. (2009).
Genes to Cells 14(8):991-1001. PMID: 19624751
Inhibition of IGF-1 signaling and growth by the fasting-induced hormone FGF21.
Inagaki T., Lin V.Y., Goetz R., Mohammadi M., Mangelsdorf D.J., Kliewer S.A. (2008).
Cell Metab. 8(1), 77-83. PMID: 18585098
Endocrine regulation of the fasting response by PPARα-mediated induction of fibroblast growth factor 21.
Inagaki T., Dutchak P., Zhao G., Ding X., Gautron L., Parameswara V., Li Y., Goetz R., Mohammadi M., Esser V., Elmquist J.K., Gerard R.D., Burgess S.C., Hammer R.E., Mangelsdorf D.J., Kliewer S.A. (2007).
Cell Metab. 5(6), 415-425. PMID: 17550777
Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor.
Inagaki T., Moschetta A., Lee Y-K, Peng L., Zhao G., Downes M., Yu R.T., Shelton J.M., Richardson J.A., Repa J.J., Mangelsdorf D.J., Kliewer S.A. (2006).
Proc. Natl. Acad. Sci. USA. 103(10), 3920-3925. PMID: 16473946
Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis.
Inagaki T., Choi M., Moschetta A., Peng L., Cummins C.L., McDonald J.G., Luo G., Jones S.A., Goodwin B., Richardson J.A., Gerard R.D., Repa J.J., Mangelsdorf D.J., Kliewer S.A. (2005).
Cell Metab. 2(4), 217-225. PMID: 16213224
The retinoic acid-responsive proline-rich protein is identified in promyeloleukemic HL-60 cells.
Inagaki T., Suzuki S., Miyamoto T., Takeda T., Yamashita K., Komatsu A., Yamauchi K., Hashizume K. (2003).
J. Biol. Chem. 278(51), 51685-92. PMID: 14530287
・Lilly Award, Japan Diabetes Society (2018)
・Research Encouragement Award, Japan Endocrine Society (2016)
・Okamoto Research Encouragement Award, Foundation for the Promotion of Adult Vascular Disease Research (2012)
E-mail: inagaki[at]gunma-u.ac.jp
Phone: +81-27-220-8880
Address:
Institute for Molecular and Cellular Regulation
Gunma University
3-39-15 Showa-machi, Maebashi,
Gunma 371-8512, Japan