Message from the Professor

Welcome to Shimano’s Lab

Our group intends to mix-up clinical services, basic research, and comprehensive education to contribute to global public health. It is unique in a medical department of Japanese national university, because many researchers from a wide variety of fields and backgrounds MD, PhD from many countries are gathering into one purpose : Enjoy lipid research for your own personal purpose: maybe you just like experiments, you would publish the paper, to get the thesis and graduate, to get the next carrier,,,,

Find the truth out of curiosity to fulfill your own purposes

We have been working to understand the molecular mechanisms of energy metabolism using the newest technologies, such as molecular and cellular biology, gene-engineered animals, genome informatics and trans-omics including lipidomics. We especially focus on lipid metabolism with our original molecular targets: SREBPs, CREBH, Elovl6, CtBP2, and KLF15 (see details in each section) develop new therapeutic approaches for preventing obesity, diabetes, and cardiovascular disease.
Our work has been known worldwide and highly estimated in uniqueness and originality, for instance, showing that modification of tissue fatty acid composition could be a new strategy for obesity–related disorders (insulin resistance, atherosclerosis, and steato-hepatitis) without amelioration of obesity. The findings and concept are deeply involved in a wide variety of diseases including not only metabolic diseases such as diabetes, dyslipidemia, and cardiovascular diseases, but also chronic inflammatory diseases and even cancers. Our recent attempts to reveal novel functions of tissue fatty acids might help understanding of broader biology including brain and mental function and disorders linking to life-related diseases.
We reveal that these factors regulate organ lipids in both quantity and quality aspects and energy metabolism, and thus, play pivotal roles in a wide variety of biological and pathological events. Our lab motto is “BREAK the DOGMA”. We always try to open up a new world of science with pieces of novel wisdom to contribute to future therapy for inflammation, cancer, and brain sciences beyond endocrinological and metabolic diseases.

Projects for Graduate Students: Major medical of Sciences, Master’s program, HBP, and Humanics
For master students:
Research on energy metabolism and transcription factors.
Research on lipid metabolism for various metabolic diseases.
Research on pathogenic mechanisms and treatment of diabetes.
Research on pathogenic mechanisms and treatment of atherosclerosis.
Study Programs for Short Stay Students (one week ~ one trimester):
Transfection and Luciferase assay for analyzing the function of transcription factors.
Experimental procedures for mouse metabolic disease model.

Profile

Professor Shimano received his M.D. and Ph.D. from the University of Tokyo in Japan. After postdoctoral research in Nobel prize laureate laboratory of Goldstein, and Brown lab at UT Southwestern medical center in Texas, he extended his work on the transcriptional regulation of cholesterol metabolism to fatty acid metabolism, and established now well-recognized aspects of transcription regulation study: a crosstalk network of transcription factors in energy metabolism. His research interests are now shifted to energy sensing system of starvation and satiety in vivo and unknown roles of tissue fatty acids for cellular physiological and pathological signals.
His work has been known worldwide and highly estimated in uniqueness and originality, for instance, showing that modification of tissue fatty acid could be a new strategy for obesity–related disorders (insulin resistance, atherosclerosis, and steato-hepatitis) without amelioration of obesity. His findings and concept are deeply involved in a wide variety of diseases including not only metabolic diseases such as diabetes, dyslipidemia, and cardiovascular diseases, but also chronic inflammatory diseases and even cancers. His recent attempts to reveal novel functions of tissue fatty acids might help understanding of broader biology including atherosclerosis, insulin resistance, and brain function and disorders linking to life-related diseases.

Selected Publications
1. Shimano H., Sato R. SREBP-regulated lipid metabolism: convergent physiology – divergent pathophysiology. Nat Rev Endocrinol. 2017 Dec; 13(12):710-730.
2. Oishi Y, Spann NJ, Link VM, Muse ED, Strid T, Edillor C, Kolar MJ, Matsuzaka T, Hayakawa S, Tao J, Kaikkonen MU, Carlin AF, Lam MT, Manabe I, Shimano H, Saghatelian A, Glass CK. SREBP1 Contributes to Resolution of Pro-inflammatory TLR4 Signaling by Reprogramming Fatty Acid Metabolism.  Cell Metab. 2017 Feb 7; 25(2): 412-427.
3. Zhao H, Matsuzaka T, Nakano Y, Motomura K, Tang N, Yokoo T, Okajima Y, Han SI, Takeuchi Y, Aita Y, Iwasaki H, Yatoh S, Suzuki H, Sekiya M, Yahagi N, Nakagawa Y, Sone H, Yamada N, Shimano H. Elovl6 Deficiency Improves Glycemic Control in Diabetic db/db Mice by Expanding β-Cell Mass and Increasing Insulin Secretory Capacity. Diabetes. 2017 Jul; 66(7): 1833-1846.
4. Takeuchi Y, Yahagi N, Aita Y, Murayama Y, Sawada Y, Piao X, Toya N, Oya Y, Shikama A, Takarada A, Masuda Y, Nishi M, Kubota M, Izumida Y, Yamamoto T, Sekiya M, Matsuzaka T, Nakagawa Y, Urayama O, Kawakami Y, Iizuka Y, Gotoda T, Itaka K, Kataoka K, Nagai R, Kadowaki T, Yamada N, Lu Y, Jain MK, Shimano H. KLF15 Enables Rapid Switching between Lipogenesis and Gluconeogenesis during Fasting. Cell Rep. 2016 Aug 30; 16(9): 2373-2386.
5. Sunaga H, Matsui H, Ueno M, Maeno T, Iso T, Syamsunarno MR, Anjo S, Matsuzaka T, Shimano H, Yokoyama T, Kurabayashi M. Deranged fatty acid composition causes pulmonary fibrosis in Elovl6-deficient mice. Nat Commun. 2013; 4: 2563.
6. Izumida Y, Yahagi N, Takeuchi Y, Nishi M, Shikama A, Takarada A, Masuda Y, Kubota M, Matsuzaka T, Nakagawa Y, Iizuka Y, Itaka K, Kataoka K, Shioda S, Niijima A, Yamada T, Katagiri H, Nagai R, Yamada N, Kadowaki T, Shimano H. Glycogen shortage during fasting triggers liver-brain-adipose neurocircuitry to facilitate fat utilization. Nat Commun. 2013; 4: 2316.
7. Matsuzaka T, Atsumi A, Matsumori R, Nie T, Shinozaki H, Suzuki-Kemuriyama N, Kuba M, Nakagawa Y, Ishii K, Shimada M, Kobayashi K, Yatoh S, Takahashi A, Takekoshi K, Sone H, Yahagi N, Suzuki H, Murata S, Nakamuta M, Yamada N, Shimano H. Elovl6 promotes nonalcoholic steatohepatitis in mice and humans. Hepatology. 2012 Dec; 56(6): 2199-2208.
8. Matsuzaka T, Shimano H, Yahagi N, Kato T, Atsumi A, Yamamoto T, Inoue N, Ishikawa M, Okada S, Ishigaki N, Iwasaki H, Iwasaki Y, Karasawa T, Kumadaki S, Matsui T, Sekiya M, Ohashi K, Hasty AH, Nakagawa Y, Takahashi A, Suzuki H, Yatoh S, Sone H, Toyoshima H, Osuga J & Yamada N. Crucial role of a long-chain fatty acid elongase, Elovl6, in obesity-induced insulin resistance.Nat Med 2007 Oct; 13(10): 1193-1202.
9. Kato T, Shimano H, Yamamoto T, Yokoo T, Endo Y, Ishikawa M, Matsuzaka T, Nakagawa Y, Kumadaki S, Yahagi N, Takahashi A, Sone H, Suzuki H, Toyoshima H, Hasty AH, Takahashi S, Gomi H, Izumi T, Yamada N. Granuphilin is activated by SREBP-1c and involved in impaired insulin secretion in diabetic mice. Cell Metab 4(2): 143-54, 2006 Aug
10. Nakagawa Y, Shimano H, Yoshikawa T, Ide T, Tamura M, Furusawa M, Yamamoto T, Inoue N, Matsuzaka T, Takahashi A, Hasty AH, Suzuki H, Sone H, Toyoshima H, Yahagi N, and Yamada N. TFE3 transcriptionally activates hepatic IRS-2, participates in insulin-signaling and , ameliorates diabetes. Nat Med 12(1): 107-13, 2006 Jan [Epub 2005 Dec 4]
11. Ide T, Shimano H, Yahagi N, Matsuzaka T, Nakakuki M, Yamamoto T, Nakagawa Y, Takahashi A, Suzuki H, Sone H, Toyoshima H, Fukamizu A, Yamada N. SREBPs suppress IRS-2-mediated insulin signaling in the liver. Nature Cell Biology 6(4): 351-7, 2004 Apr