Research Areas:

A balanced immune homeostasis is crucial to health. Both overactive and insufficient immune responses create problems. Excessive or chronic immune activation is known to contribute to pathogenesis of various diseases, like obesity, diabetes, rheumatic diseases, autoimmunity, lethal cytokine storms etc. Conversely, insufficient immune response impair defense against pathogens, and even contribute to tumorigenesis. Over the past decades, both repressive and active immunoregulators have been found in emission of injured tissues and stressed/dying cells, but the relevant understanding of their immunogenicity remains limited, and limited attention has been dedicated to comprehensively identify and characterize these stressed/dying cells derived immunoregulators. Thus, we will utilize approaches including biochemical, cellular, molecular, multi-omics etc. to identify and characterize potent immunoregulators emitted from stressed/dying cells, decipher their biogenesis and physio-pathological functions, aim to provide novel strategies and targets for diagnosis, treatment, and prognosis of inflammation relevant diseases.

We have demonstrated extrachromosomal circular DNA (eccDNA) of a few hundred bp as a circularized product of apoptotic DNA fragments and shows potent immunostimulatory activity in vitro. Due to technical challenges, physio-pathological roles of eccDNAs remain to be explored, and the same goes with their regulations in vivo. To address these questions, we determine to crash technical obstacles via developing novel tools and strategies, eventually to reveal the nature of eccDNAs, particularly under pathological contexts.

Brief Biography:

Jan/2023-now: Principal Investigator, Shanghai Institute of Nutrition and Health, CAS, Shanghai, China

Oct/2017-Jan/2023: Postdoc Fellow, Boston Children's Hospital, Harvard Medical School. Boston, MA, USA

Aug/2015-Sep/2017: Research Associate, Shanghai Institutes for Biological Sciences, CAS. Shanghai, China

Sep/2008-Jul/2015: Ph.D, Shanghai Institutes for Biological Sciences, CAS. Shanghai, China

Sep/2004-Jul/2008: B.S, Wuhan University, Wuhan City, Hubei province, China

Selected Publications: (^#The first author, *Corresponding)

1. Wang Y^#, Wang M, Zhang Y*. Purification, full-length sequencing, and genomic origin mapping of eccDNA. Nat Protoc 2023 Mar;18(3):683-699.
2. Wang Y^#, Wang M, Djekidel MN, Chen H, Liu D, Alt FW, Zhang Y*. eccDNAs are apoptotic products with high innate immunostimulatory activity. Nature 2021 Nov;599(7884):308-314.
3. Dang F, Nie L, Zhou J, Shimizu K, Chu C, Wu Z, Fassl A, Ke S, Wang Y, Zhang J, Zhang T, Tu Z, Inuzuka H, Sicinski P, Bass AJ, Wei W*. Inhibition of CK1ε potentiates the therapeutic efficacy of CDK4/6 inhibitor in breast cancer. Nat Commun 2021 Sep 10;12(1):5386.
4. Sun H, Wang J, Gong Z, Yao J, Wang Y, Xu J, Yuan GC, Zhang Y, Shao Z*. Quantitative integration of epigenomic variation and transcription factor binding using MAmotif toolkit identifies an important role of IRF2 as transcription activator at gene promoters. Cell Discov 2018 Jul 10;4:38.
5. Luan Y, Zhang F, Cheng Y, Liu J, Huang R, Yan M, Wang Y, He Z, Lai H, Wang H, Ying H, Guo F, Zhai Q*. Hemin Improves Insulin Sensitivity and Lipid Metabolism in Cultured Hepatocytes and Mice Fed a High-Fat Diet. Nutrients 2017 Jul 26;9(8):805.
6. Liu J, Zhou B, Yan M, Huang R, Wang Y, He Z, Yang Y, Dai C, Wang Y, Zhang F, Zhai Q*. CLOCK and BMAL1 regulate muscle insulin sensitivity via SIRT1 in male mice. Endocrinology 2016 Jun 1;157(6):2259-2269.
7. Wang Y^#, Hu Y, Sun C, Zhuo S, He Z, Wang H, Yan M, Liu J, Luan Y, Dai C, Yang Y, Huang R, Zhou B, Zhang F, Zhai Q*. Down-regulation of Risa improves insulin sensitivity by enhancing autophagy. FASEB J 2016 Sep;30(9):3133-3145.
8. Zhou B, Zhang Y, Zhang F, Xia Y, Liu J, Huang R, Wang Y, Hu Y, Wu J, Dai C, Wang H, Tu Y, Peng X, Wang Y, Zhai Q*. CLOCK/BMAL1 regulates circadian change of mouse hepatic insulin sensitivity by SIRT1. Hepatology 2014 Jun;59(6):2196-2206.
9. Yan M, Wang Y, Hu Y, Feng Y, Dai C, Wu J, Wu D, Zhang F, Zhai Q*. A high-throughput quantitative approach reveals more small RNA modifications in mouse liver and their correlation with diabetes. Anal Chem 2013 Dec 17;85(24):12173-81.
10. Zhang Y, Zhou B, Deng B, Zhang F, Wu J, Wang Y, Le Y, Zhai Q*. Amyloid-β induces hepatic insulin resistance in vivo via JAK2. Diabetes 2013 Apr 1;62(4):1159-1166.