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基因表達(dá)調(diào)控驅(qū)動代謝重塑

代謝重塑是細(xì)胞和組織適應(yīng)環(huán)境變化的重要生物學(xué)過程，其異常與肥胖、糖尿病、癌癥等重大疾病密切相關(guān)。代謝重塑依賴于精細(xì)的基因表達(dá)調(diào)控，因此，全面解析代謝重塑的基因表達(dá)調(diào)控機(jī)制是實現(xiàn)代謝性疾病精準(zhǔn)干預(yù)的重要基礎(chǔ)。研究組致力于研究基因表達(dá)調(diào)控如何驅(qū)動代謝重塑，重點解析細(xì)胞如何將遺傳信息和環(huán)境刺激轉(zhuǎn)化為特定的基因表達(dá)程序，從而實現(xiàn)代謝適應(yīng)。通過結(jié)合三維基因組學(xué)、功能基因組學(xué)、單細(xì)胞組學(xué)、表觀遺傳學(xué)、高通量篩選及基因編輯等前沿技術(shù)，系統(tǒng)研究基因表達(dá)調(diào)控與代謝重塑之間的分子聯(lián)系，并探索其在代謝性疾病中的轉(zhuǎn)化應(yīng)用。主要研究方向包括：（1）三維基因組與代謝性疾病遺傳機(jī)制；（2）代謝物與細(xì)胞間通訊介導(dǎo)的代謝反饋。

1.?Zhang Y^#, Zheng RB^#, Tsuji T, Wang CH, Liu XY, Xing YH, Darcy J, Lynes MD, Lundh M, Arianti R, Gy?ry F, Dong R, Emanuelli B, Johnstone SE, Rivera MN, Kristóf E, Kahn CR, Chen KF*, Tseng YH*. A conserved hormonal signalling–H2A. Z axis rapidly reorganizes 3D chromatin interactions in adipocyte thermogenesis. Nature Metabolism 2026 May, 8(5): 1086-1105.

2. Zheng RB^#, Zhang Y^#, Tsuji T, Gao XL, Shamsi F, Wagner A, Yosef N, Cui K, Chen H, Kiebish M, Aristizabal-Henao J, Narain N, Zhang LL, Tseng YH*, Chen KF*. MEBOCOST maps metabolite-mediated intercellular communications using single-cell RNA-seq. Nucleic Acids Research 2025 Jun 20, 53(12): gkaf569.

3.?Zhang Y, Nguyen TM, Zhang XO, Wang LM, Phan T, Clohessy JG*, Pandolfi PP*. Optimized RNA-targeting CRISPR/Cas13d technology outperforms shRNA in identifying functional circRNAs. Genome Biology 2021 Jan 21, 22(1): 41.

4.?Zhang Y, Yang L and Chen LL*. Characterization of circular RNAs. Methods in Molecular Biology 2021, 2372: 179-192.

5. Nguyen TM^#, Zhang Y^#, Pandolfi PP*. Virus against virus: a potential treatment for 2019-nCov (SARS-CoV-2) and other RNA viruses. Cell Research 2020 Mar, 30(3): 189-190.

6. Xing YH^#, Yao RW^#, Zhang Y^#, Guo CJ, Jiang S, Xu G, Dong R, Yang L, Chen LL*. SLERT regulates DDX21-rings associated with Pol I transcription. Cell 2017 May 4, 169(4): 664-678. (Research highlights by Bull Chin Acad Sci, 2017, 31: 152-155)

7.?Zhang Y^#, Xue W^#, Li X, Zhang J, Zhang JL, Yang L*, Chen LL*. The biogenesis of nascent circular RNAs. Cell Reports 2016 Apr 19, 15(3): 611-624.

8. Zhang XO^#, Dong Rui^#, Zhang Y^#, Zhang JL, Luo Z, Zhang J, Chen LL*, Yang L*. Diverse alternative back-splicing and alternative splicing landscape of circular RNAs. Genome Research 2016 Sep, 26(9):1277-1287.

9.?Zhang Y, Yang L and Chen LL*. Characterization of circular RNAs. Methods in Molecular Biology 2016, 1402: 215-227.

10.?Zhang Y, Yang L and Chen LL*. Life without A tail: new formats of long noncoding RNAs. The International Journal of Biochemistry & Cell Biology 2014 Sep, 54: 338-349.

11.?Zhang Y^#, Zhang XO^#, Chen T, Xiang JF, Yin QF, Xing YH, Zhu S, Yang L* and Chen LL*. Circular intronic long noncoding RNAs. Molecular Cell 2013 Sep 26, 51(6): 792-806. (Issue Highlight; Preview by Bolisetty MT and Graveley BR, Mol Cell, 2013, 51: 705-706; Research Highlights by Nature, 2013, 501:464; Research Highlights by Nature China, 2013, doi:10.1038)

12. Tsuji T, Tolstikov V, Zhang Y, Huang TL, Camara H, Halpin M, Narain NR, Yau KW, Lynes MD, Kiebish MA, Tseng YH*. Light-responsive adipose-hypothalamus axis controls metabolic regulation. Nature Communications 2024 Aug 8, 15(1): 6768.

13. Tsuji T, Zhang Y, Tseng HY*. Generation of Brown Fat-Specific Knockout Mice Using a Combined Cre-LoxP, CRISPR-Cas9, and Adeno-Associated Virus Single-Guide RNA System. Journal of Visualized Experiments 2023 Mar 24, 193: 10.3791/65083.

14. Guarnerio J, Zhang Y, Cheloni G, Panella R, Mae Katon J, Simpson M, Matsumoto A, Papa A, Loretelli C, Petri A, Kauppinen S, Garbutt C, Nielsen GP, Deshpande V, Castillo-Martin M, Cordon-Cardo C, Dimitrios S, Clohessy JG, Batish M, Pandolfi PP*. Intragenic antagonistic roles of protein and circRNA in tumorigenesis. Cell Research 2019 Aug, 29(8): 628-640.

15. Lee YR, Chen M, Lee JD, Zhang J, Lin SY, Fu TM, Chen H, Ishikawa T, Chiang SY, Katon J, Zhang Y, Shulga YV, Bester AC, Fung J, Monteleone E, Wan L, Shen C, Hsu CH, Papa A, Clohessy JG, Teruya-Feldstein J, Jain S, Wu H, Matesic L, Chen RH, Wei W, Pandolfi PP*. Reactivation of PTEN tumor suppressor for cancer treatment through inhibition of a MYC-WWP1 inhibitory pathway. Science 2019 May 17, 364(6441): eaau0159.

16. Li X, Liu CX, Xue W, Zhang Y, Jiang S, Yin QF, Wei J, Yao RW, Yang L, Chen LL*. Coordinated circRNA Biogenesis and Function with NF90/NF110 in Viral Infection. Molecular Cell 2017 Jul 20, 67(2): 214-277. (Featured Article; Highlighted by Editor’s Note and Meet the Authors)

17. Dong R, Zhang XO, Zhang Y, Ma XK, Chen LL*, Yang L*. CircRNA-derived pseudogenes. Cell Research 2016 Jun, 26(6):747-750.

18. Zhang XO^#, Wang HB^#, Zhang Y, Lu X, Chen LL* and Yang L*. Complementary sequence-mediated exon circularization. Cell 2014 Sep 25, 159(1): 134-147. (Featured Article; Research highlights by Nat Rev Genetics, 2014, 15:717; Research highlights by Bull Chin Acad Sci, 2014, 28: 282-284; F1000 Prime recommendataion)

19. Xiang JF, Yin QF, Chen T, Zhang Y, Zhang XO, Wang HB, Ge JH, Lu XH, Yang L and Chen LL*. Human colorectal cancer-specific CCAT1-L lncRNA regulates long-range chromatin interactions in the MYC locus. Cell Research 2014 May, 24(5): 513-531. (Cover Article and Issue Highlights)

20.?Yin QF^#, Yang L^#, Zhang Y, Xiang JF, Wu YW, Carmichael GG* and Chen LL*. Long noncoding RNAs with snoRNA ends. Molecular Cell 2012 Oct 26, ?48(2): 219-230. (Cover Article; Preview by Mol Cell, 2012, 48:155-7; Research Highlights by Nat Rev Mol Cell Biol, 2012, 13:686, Best of Molecular Cell 2012)