Liangyou Rui

Liangyou Rui, PhD

Louis G. D'Alecy Collegiate Professor of Physiology
Professor, Molecular and Integrative Physiology
Professor, Internal Medicine, Medical School

North Campus Research Complex
2800 Plymouth Rd
Building 20E, Office 3825
Ann Arbor, MI 48109

ruily@umich.edu
(734) 615-7542
Articles ↓ Web Sites ↓

Areas of Interest

The Rui laboratory investigates obesity, diabetes, metabolic dysfunction-associated steatohepatitis (MASH), and liver cancer. At the physiological level, we study hypothalamic neurocircuits controlling body weight and metabolism, liver metabolism/injury/regeneration/fibrosis, adipose growth/function, and crosstalk between fat, liver, and the brain. At the molecular level, we are interested in epigenetics, RNA modifications, RNA fate, and proteostasis controlled by RNA-binding proteins, and signal transduction.

Neurocircuits controlling body weight and metabolism. (1) We identified neuronal SH2B1 as a critical anti-obesity protein. We generated several unique SH2B1 mouse models (conditional Sh2b1 knockout, SH2B1 overexpression, SH2B1 cell-lineage tracing). Using these models, we map hypothalamic SH2B1 neurocircuits and delineate how SH2B1 regulates, through these neurocircuits, food intake, energy expenditure, body weight, and metabolism. (2) We identified hypothalamic Slug/Snai2 as a pro-obesity transcription factor. Slug promotes histone modifications and epigenetic reprogramming by recruiting epigenetic modifiers. Our goal is to elucidate how Slug-elicited epigenetic reprogramming/memory impairs energy balance neurocircuits to promote obesity and metabolic disease progressions. (3) We are interested in RNA modifications, particularly N6-methyladenosine (m6A). A METTL3/METTL14 methyltransferase complex, called m6A writer, deposits m6A on mRNA or noncoding RNA. A group of m6A-dependent RNA-binding proteins (YTHDF1-3, YTHDC1-2), known as m6A readers, critically regulate the metabolism and fate of m6A-modified transcripts, thereby governing protein biosynthesis and intracellular proteostasis. We study how m6A writers and m6A readers regulate the development and function of hypothalamic energy balance neurocircuits.

Liver metabolism, homeostasis, and chronic liver disease. (1) We found that liver TRAF2, TRAF3, and NIK (also called MAP3K14)―inflammatory proteins―promote type 2 diabetes. We reported that aberrant activation of hepatic or biliary NIK drives liver injury, inflammation, and fibrosis while inhibiting liver regeneration. Our goal is to elucidate individual components of TRAF2, TRAF3, and NIK pathways in hepatocytes and cholangiocytes and delineate how they influence liver injury, inflammation, regeneration, and fibrosis. (2) We investigate how hepatic and biliary TRAF2, TRAF3, and NIK pathways influence liver tumorigenesis―hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). We explore new therapeutic strategies for MASH, HCC, and iCCA by pharmacologically targeting TRAF2, TRAF3, and/or NIK pathways. (3) We are interested in RNA m6A writers and m6A readers in hepatocytes and cholangiocytes. We investigate how hepatic and biliary m6A pathways regulate liver metabolism, injury, regeneration, fibrosis, and tumorigenesis in the settings of diet-induced obesity and alcohol-associated liver disease.

Adipose growth and function. (1) We found that Snai1 and Snai2 regulate adipose tissue growth. Given that Snai1 and Snai2 recruit epigenetic modifies to chromatins, we investigate how Snai1/2-elicited epigenetic reprogramming regulates white, brown, and beige adipogenesis. (2) We reported that METTL14-induced RNA m6A modification profoundly suppresses adipose β adrenergic signaling and lipolysis, thus promoting obesity and metabolic syndrome. Our objective is to understand how adipose m6A writers, m6A readers, and epitranscriptomic editing regulate white, brown, and beige adipose growth, function, obesity, and metabolic disorders. (3) We found that brown adipose tissue profoundly influences liver steatosis and liver injury in alcohol-associated liver disease. We explore white fat- and brown fat-secreted mediators (adipokines) that mediate the interplay between fat, liver, and the brain in the settings of diet-induced obesity and alcohol associated liver disease. We also search for liver-derived mediators (hepatokines, cholangiokines), or liver cancer-secreted factors, which mediate crosstalk between liver, fat, and the brain.

Honors & Awards

  • Career Development Award, the American Diabetes Association
  • Diabetes and Obesity Biologics Science Forum Award, Novo Nordisk, Denmark
  • Fellow of the American Association for the Advancement of Science
  • Scientific Achievement Award, the Chinese-American Diabetes Association (CADA), USA

Credentials

  • Ph.D., University of Michigan, Ann Arbor, Michigan, 1998
  • Postdoctoral Fellowship, Joslin Diabetes Center, Harvard Medical School, Boston, MA, 2002

Published Articles or Reviews

  • Decheng Ren, Minghua Li, Chaojun Duan, Liangyou Rui. Identification of SH2-B as a key regulator of leptin sensitivity, energy balance, and body weight in mice. Cell Metabolism, 2:95-104, 2005. PMID:16098827.
  • Decheng Ren, Yingjiang Zhou, David Morris, Minghau Li, Zhiqin Li, Liangyou Rui. Neuronal SH2B1 is essential for controlling energy and glucose homeostasis. Journal of Clinical Investigation, 117:397-406, 2007. PMC1765516.
  • Wei Song, Decheng Ren, Wenjun Li, Lin Jiang, Kae Won Cho, Ping Huang, Chen Fan, Yiyun Song, Yong Liu, Liangyou Rui. SH2B regulation of growth, metabolism and longevity in both insects and mammals. Cell Metabolism, 11:427-437, 2010. PMC 2881875.
  • Liang Sheng, Yingjiang Zhou, Zheng Chen, Decheng Ren, Kae Won Cho, Lin Jiang, Yoshiteru Sasaki, Liangyou Rui.  NF-kB-inducing kinase (NIK) promotes hyperglycemia and glucose intolerance in obesity by augmenting glucagonaction. Nature Medicine, 18 (6):943-949, 2012. PMC3766969.
  • Hong Shen, Liang Sheng, Lin Jiang, Haoran Su, Zheng Chen, Lei Yin, M. Bishr Omary, Liangyou Rui. Mouse hepatocyte overexpression of NF-κB-inducing kinase (NIK) triggers a fatal macrophage-dependent liver injury and fibrosis. Hepatology, 60(6):2065-76, 2014. PMC4245385.
  • Bijie Jiang, Hong Shen, Zheng Chen, Lei Yin, Linsen Zan, Liangyou Rui. Carboxyl Terminus of HSC70-interacting Protein (CHIP) Downregulates NF-κB-inducing Kinase (NIK) and Suppresses NIK-induced Liver Injury. Journal of Biological Chemistry, 290(18):11704-14, 2015. PMC4416871.
  • Zheng Chen, Mark J. Canet, Liang Sheng, Lin Jiang, Yi Xiong, Lei Yin, Liangyou Rui. Hepatocyte TRAF3 promotes insulin resistance and type 2 diabetes in mice with obesity. Molecular Metabolism, 4(12):951-60, 2015. PMC4731737.
  • Chengxin Sun, Lin Jiang, Yan Liu, Hong Shen, Stephen J. Weiss, Yifa Zhou, Liangyou Rui. Adipose Snail1 Governs Lipolysis and Lipid Partitioning by Epigenetically Suppressing Adipose Triacylglycerol Lipase expression. Cell Reports, 17(8) :2015-2027, 2016. PMC5131732
  • Yan Liu, Liang Sheng, Yi Xiong, Hong Shen, Yong Liu, Liangyou Rui. Liver NF-κB-inducing kinase (NIK) promotes liver steatosis and glucose counterregulation in male mice with obesity.  Endocrinology, 158:1207-1216, 2017. PMC5460833.
  • Hong Shen, Liang Sheng, Yi Xiong, Yeunghyen Kim, Lin Jiang, Zheng Chen, Yong Liu, Cheong-Hee Chang, Liangyou Rui. NF-κB-inducing kinase (NIK) deficiency induces CD4+ T cell-elicited liver injury and fibrosis in mice.  Journal of Hepatology, 67(1):100-109, 2017. PMC5476485.
  • Yan Liu, Lin Jiang, Chengxin Sun, Nicole Ireland, Yatrik M. Shah, Yong Liu, Liangyou Rui. Insulin/Snail1 axis ameliorates fatty liver disease by epigenetically suppressing lipogenesis. Nature Communications, 9(1):2751, 2018. PMC6048127.
  • Yi Xiong, Adriana Souza Torsoni, Feihua Wu, Hong Shen, Yan Liu, Mark J Canet, Lei Yin, M. Bishr Omary, Liangyou Rui. Hepatic NF-κB-inducing kinase (NIK) suppresses mouse liver regeneration in acute and chronic liver diseases. Elife, Aug 2;7.pii:e34152, 2018. PMC6078493.
  • Hong Shen, Lin Jiang, Jiandie D. Lin, M. Bishr Omary, Liangyou Rui. Brown fat protects against alcoholic liver disease. Journal of Clinical Investigation, 130:2305-2317, 2019. PMC6546460.
  • Hong Shen, Yewei Ji, Yi Xiong, Hana Kim, Michelle G. Jin, Yatrik M. Shah, M. Bishr Omary, Yong Liu, Ling Qi, Liangyou Rui. Medullary thymic epithelial NF-κB-inducing kinase (NIK)/IKKα pathway shapes lung and liver homeostasis. Proceedings of the National Academy of Sciences of USA, 116(38):19090-19097, 2019. PMC6754592.
  • Lin Jiang, Haoran Su, Xiaoyin Wu, Hong Shen, Min-Hyun Kim, Martin G. Myers Jr, Chung Owyang, Liangyou Rui. Hypothalamic Sh2b1 protects against obesity and metabolic diseases by activating sympathetic nerve-brown fat axis. Nature Communications, 11(1):1517, 2020. PMC7089966.
  • Yan Liu, Haiyan Lin, Lin Jiang, Qingsen Shang, Yin Lei, Jiandie D. Lin, Wen-Shu Wu, Liangyou Rui. Hepatic Slug epigenetically promotes liver lipogenesis, fatty liver disease, and type 2 diabetes. Journal of Clinical Investigation, 130 (6):2992-3004, 2020. PMC7260003.
  • Xiao Zhong, Zhiguo Zhang, Hong Shen, Yi Xiong, Yatrik M. Shah, Yong Liu, Xue-Gong Fan, Liangyou Rui. Hepatic NIK and IKKα promote liver oxidative stress, ferroptosis, and liver injury. Hepatology Communications, 5(10):1704-1720, 2021. PMC8485893.
  • Zhiguo Zhang, Xiao Zhong, Hong Shen, Liang Sheng, Anna S. Lok, M Bishr Omary, Shaomeng Wang, Liangyou Rui. Biliary NIK promotes ductular reaction, liver injury, inflammation, and fibrosis in mice. Nature Communications, 13(1):5111, 2022. PMC9427946.
  • Liangyou Rui, Jiandie Lin. Nonalcoholic steatohepatitis: from hepatic steatosis to the liver microenvironment. Annual Review of Nutrition, 42:91-113, 2022. PMCID: PMC10122183.
  • Min-Hyun Kim, Lin Liang, Yuan Li, Martin G. Myers Jr, Wen-Shu Wu, Liangyou Rui. LepRb cell-specific deletion of Slug mitigates obesity and NAFLD. Journal of Clinical Investigation, 133(4):e156722, 2023. PMC9927931.
  • Qianqian Kang, Xiaorong Zhu, Decheng Ren, Alexander Ky, Ormond A. MacDougald, Robert W. O’Rourke, Liangyou Rui. AdiposeMETTL14-elicited N6-methyladenosine promotes obesity, insulin resistance, and NAFLD through suppressing β adrenergic signaling and lipolysis. Advanced Science, e2301645, 2023. PMID: 37526326.
  • Pingping Wang, Qianqian Kang, Wen-Shu Wu, Liangyou Rui. Hepatic Snai1 and Snai2 promote liver regeneration and suppress liver fibrosis in mice. Cell Reports, 43(3)113875, 2024. PMID: 38451818.

Additional Publications in Pubmed

Web Sites

Rui Lab