2001.09~2005.07,清華大學,生物科學與技術(shù)系,本科
2005.08~2010.01,美國明尼蘇達大學,藥理系,博士
2010.01~2010.09,美國明尼蘇達大學,藥理系,博士后研究助理
2010.09~至今,中國科學院廣州生物醫(yī)藥與健康研究院,研究員
鄭輝研究員長期致力于研究不同細胞命運轉(zhuǎn)換過程涉及的細胞生物學機制。2010年回國后主要研究多能性轉(zhuǎn)錄因子以及細胞在不同狀態(tài)(間質(zhì)及上皮)間的相互轉(zhuǎn)化調(diào)控體細胞重編程、細胞轉(zhuǎn)分化以及腫瘤發(fā)生和發(fā)展過程的具體機制,涉及細胞生物學、神經(jīng)生物學、表觀遺傳學、腫瘤以及藥理學。?
鄭輝研究員及其團隊在早期研究中揭示了EMT/MET對體細胞重編程的重要調(diào)控作用(Nat Cell Biol,2013),并提出了“EMT-MET調(diào)控細胞命運”的重要理論(Cell Res,2014;Protein & Cell,2014),受到領(lǐng)域內(nèi)的廣泛認可。2017年,利用該理論成功指導成纖維細胞向神經(jīng)細胞轉(zhuǎn)分化的研究(Cell Discovery, 2017)。此后,圍繞EMT對多能性和神經(jīng)譜系細胞命運的調(diào)控作用,從細胞能量代謝和DNA甲基化兩個角度開展研究。一方面,揭示了細胞能量代謝與EMT之間的正反饋調(diào)控對多能性重建的時間依賴性調(diào)控機制,建立了獲得新型多能干細胞的技術(shù)體系(EMBO J,2020,封面)。另一方面,揭示了DNA甲基化與EMT之間的負反饋調(diào)控機制,建立了通過影響DNA甲基化調(diào)控細胞命運的新技術(shù)體系(Cell Reports,2020;Cell Discovery,?2019;JBC, 2018)。在多能性重建和神經(jīng)細胞轉(zhuǎn)分化的過程中,將EMT、細胞能量代謝以及DNA甲基化有機地整合了起來。目前,鄭輝研究員及其團隊正嘗試在更多細胞命運轉(zhuǎn)換過程中整合細胞更多類型的變化,繪制細胞命運的普適性調(diào)控模型。
鄭輝研究員曾作為負責人承擔過或正在承擔包括國家自然科學基金(創(chuàng)新研究群體-核心成員、重大科學研究計劃-集成項目、廣東省-NSFC聯(lián)合基金-重點項目、優(yōu)秀青年科學項目、面上項目、青年項目等)以及中國科學院先導科技專項(子課題負責人)在內(nèi)的多項國家以及省市級科研項目。鄭輝研究員目前合計發(fā)表52篇論文,作為通訊作者或者共同通訊作者發(fā)表論文36篇(Nat Cell Biol, EMBO J, PNAS, Cell Reports, Biol Psychiatry, Neuropsychopharmacol, J Neurosci等),作為第一作者發(fā)表論文1篇(除去同時是通訊作者的論文),作為共同作者發(fā)表論文15篇。合計影響因子超過300,合計引用次數(shù)超過1500次,合計他引次數(shù)超過1200次。鄭輝研究員獲得2017年中國科學院杰出科技成就獎-重要成員(7/17),2018年國家自然科學獎二等獎(4/5),2018年廣東省自然科學獎二等獎(1/10)。
鄭輝博士現(xiàn)擔任IUBMB Life, Frontiers in Cellular Endocrinology等國際性學術(shù)雜志的編委。同時曾擔任國際干細胞研究學會(ISSCR)2014年年會摘要評審、國家自然科學基金項目評審、香港研究資助局(RGC)項目外部評審、科技部創(chuàng)新人才推進計劃評審。
指導碩士研究生12名,博士研究生8名。其中,2名畢業(yè)生已晉升副研究員。2019年畢業(yè)博士研究生(孫昊):在學期間獲得中國科學院杰出科技成就獎(14/17);畢業(yè)時獲得“優(yōu)秀畢業(yè)生”、“地奧二等獎學金”;畢業(yè)后已晉升副研究員,獲得國家自然科學基金青年項目支持。2018年畢業(yè)博士研究生(梁麗寧):留院后先后成為特別研究助理和副研究員,獲得中科院特別研究助理項目和國家自然科學基金青年項目支持。培養(yǎng)的研究生(在學期間)作為第一或者通訊作者合計發(fā)表25篇論文(Nat Cell Biol, EMBO J, Biol Psychiatry,Cell Reports等),合計影響因子超過200,合計引用次數(shù)超1000次;培養(yǎng)的研究生(在學期間)獲得廣東省自然科學獎二等獎3人次(排名前五)。
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*代表通訊作者?
第一作者或者通訊作者論文?
????[37]?Liang L#, He M#, Zhang Y#, Wang C, Qin Z, Li Q, Yang T, Meng F, Zhou Y, Ge H, Song W, Chen S, Dong L, Ren Q, Li C, Guo L, Sun H, Zhang W, Pei D*, Zheng H*?Unraveling the 2,3–diketo–L–gulonic?acid–dependent and –independent impacts of L–ascorbic acid on somatic cell reprogramming. Cell & Bioscience. 2023 Nov 30;13(1):218.
[36] Li C*#, He J#, Meng F#, Wang F#, Sun H, Zhang H, Zhang M, Xu Q, Liang L, Li Y, Yang T, He M, Wang T, Lin J, Sun J, Huang Q, Guo L, Zhang X, Mai S*, Zheng H*. Nuclear Localization of TET2 Requires β-catenin Activation and Correlates with Favourable Prognosis in Colorectal Cancer. Cell Death & Disease. 2023 Aug 24;14(8):552.
[35]?Li Y#, Yang T#, Cheng Y#, Hou J#, Liu Z, Zhao Y, Chen S, Qin Z, Wang C, Song W, Ge H, Li C, Liang L, Guo L, Sun H, Wu LP*, Zheng H*. Low glutaminase and glycolysis correlate with a high transdifferentiation efficiency in mouse cortex.?Cell Proliferation.?2023 May;56(5):e13422.
????[34] Sun J#*, Yang J, Miao X, Loh HH, Pei D, Zheng H*. Proteins in DNA methylation and their role in neural stem cell proliferation and differentiation. Cell Regeneration. 2021 Mar 2;10(1):7.?
????[33] Meng F#, Li Y, Sun H, Li C, Li Q, Law PY, Loh HH, Liang L*, Zheng H*. Naloxone Facilitates Contextual Learning and Memory in a Receptor-Independent and Tet1-Dependent Manner. Cellular and Molecular Neurobiology. 2021 Jul;41(5):1031-1038.
????[32] Zhang M#, Li Q, Yang T, Meng F, Lai X, Liang L, Li C, Sun H, Sun J, Zheng H*. Positive feedback between retinoic acid and 2-phospho-L-ascorbic acid trisodium salt during somatic cell reprogramming. Cell Regeneration. 2020 Oct 1;9(1):17.
????[31] Lai X#, Li Q#, Wu F, Lin J, Chen J*, Zheng H*, Guo L*. Epithelial-Mesenchymal Transition and Metabolic Switching in Cancer: Lessons From Somatic Cell Reprogramming. Frontiers in Cell and Developmental Biology. 2020 Aug 6;8:760.
[30] Chen J#, Liang L#, Li Y, Zhang Y, Zhang M, Yang T, Meng F, Lai X, Li C, He J, He M, Xu Q, Li Q, Law PY, Loh HH, Pei D, Sun H*,?Zheng H*. Naloxone regulates the differentiation of neural stem cells via a receptor-independent pathway. The?FASEB Journal. 2020 Apr;34(4):5917-5930.
????[29] Liang L#, Chen J#, Li Y, Lai X, Sun H, Li C, Zhang M, Yang T, Meng F, Law PY, Loh HH, Zheng H*. Morphine and Naloxone Facilitate Neural Stem Cells Proliferation via a TET1-Dependent and Receptor-Independent Pathway. Cell Reports. 2020 Mar 17;30(11):3625-3631.
????[28] Sun H#, Yang X#, Liang L#, Zhang M#, Li Y, Chen J, Wang F, Yang T, Meng F, Lai X, Li C, He J, He M, Xu Q, Li Q, Lin L, Pei D*, Zheng H*. Metabolic switch and epithelial-mesenchymal transition cooperate to regulate pluripotency. The EMBO Journal. 2020 Apr 15;39(8):e102961.
????[27] He S#, Wang F#, Zhang Y#, Chen J, Liang L, Li Y, Zhang M, Yang X, Pang H, Li Y, Huang X, Qin D, Pei D, Sun H*, Zheng H*. Hemi-methylated CpG sites connect Dnmt1-knockdown-induced and Tet1-induced DNA demethylation during somatic cell reprogramming. Cell Discovery. 2019 Feb 12;5:11.
[26] Lin L#, Liang L#, Yang X#, Sun H, Li Y, Pei D, Zheng H*. The homeobox transcription factor MSX2 partially mediates the effects of bone morphogenetic protein 4 (BMP4) on somatic cell reprogramming. The Journal of Biological Chemistry. 2018 Sep 21;293(38):14905-14915.
[25] He S#, Sun H#, Lin L, Zhang Y, Chen J, Liang L, Li Y, Zhang M, Yang X, Wang X, Wang F, Zhu F, Chen J, Pei D, Zheng H*. Passive DNA demethylation preferentially up-regulates pluripotency-related genes and facilitates the generation of induced pluripotent stem cells. The Journal of Biological Chemistry. 2017 Nov 10;292(45):18542-18555.
????[24] He S#, Chen J#, Zhang Y#, Zhang M, Yang X, Li Y, Sun H, Lin L, Fan K, Liang L, Feng C, Wang F, Zhang X, Guo Y, Pei D*, Zheng H*. Sequential EMT-MET induces neuronal conversion through Sox2. Cell Discovery. 2017 May 30;3:17017. ?
[23] Liang L#, Sun H, Li L, Zheng H*. Transitions between mesenchymal and epithelial states and the concomitant gene expression changes.?Science Foundation in China. 2016,24(1):50-62.?
????[22] Li L#, He S, Zheng H*. The Abilities of ShDNMT1 to Promote Reprogramming are Enhanced by Vitamin C-recused Proliferation. China Biotechnology. 2016, 36(6): 1-8.??
????[21] Sun H#, Liang L, Li Y, Feng C, Li L, Zhang Y, He S, Pei D, Guo Y*, Zheng H*. Lysine-specific histone demethylase 1 inhibition promotes reprogramming by facilitating the expression of exogenous transcriptional factors and metabolic switch. Scientific Reports. 2016 Aug 2;6:30903.
[20] Liang L#, Sun H#, Zhang W, Zhang M, Yang X, Kuang R, Zheng H*. Meta-Analysis of EMT Datasets Reveals Different Types of EMT. PLoS One. 2016 Jun 3;11(6):e0156839.
[19] Huang Z#, Liang L#, Li L#, Xu M, Li X, Sun H, He S, Lin L, Zhang Y, Song Y, Yang M, Luo Y, Loh HH, Law PY, Zheng D*, Zheng H*. Opioid doses required for pain management in lung cancer patients with different cholesterol levels: negative correlation between opioid doses and cholesterol levels. Lipids in Health and Disease. 2016 Mar 8;15:47.
????[18] Chen J#, Li W, Li Y, He S, Li L, Liang L, Song Y, Qin D*, Zheng H*. MicroRNA-128-3p impaired water maze learning by suppressing Doublecortin expression in both wild type and Aβ-42 infused mice. Neuroscience Letters. 2016 Jul 28;626:79-85.
????[17] He S#, Guo Y, Zhang Y, Li Y, Feng C, Li X, Lin L, Guo L, Wang H, Liu C, Zheng Y, Luo C, Liu Q, Wang F, Sun H, Liang L, Li L, Su H, Chen J, Pei D*, Zheng H*. Reprogramming somatic cells to cells with neuronal characteristics by defined medium both in vitro and in vivo. Cell Regeneration. 2015 Dec 30;4:12.
[16] Zheng H#, Hutchins AP, Pan G, Li Y, Pei D*, Pei G*. Where cell fate conversions meet Chinese philosophy. Cell Research. 2014 Oct;24(10):1162-3.
[15] Li X#, Pei D, Zheng H*. Transitions between epithelial and mesenchymal states during cell fate conversions. Protein Cell. 2014;5(8):580-91.
????[14] Li W#, He S#, Zhou Y, Li Y, Hao J, Zhou X, Wang F, Zhang Y, Huang Z, Li Z, Loh HH, Law PY, Zheng H*. Neurod1 modulates opioid antinociceptive tolerance via two distinct mechanisms. Biological Psychiatry. 2014 Nov 15;76(10):775-84.
????[13] Zheng H*#, Zhang Y, Li W, Loh HH, Law PY. NeuroD modulates opioid agonist-selective regulation of adult neurogenesis and contextual memory extinction. Neuropsychopharmacology. 2013 Apr;38(5):770-7.
????[12] Zheng H*#, Loh HH, Law PY. Posttranslation modification of G protein-coupled receptor in relationship to biased agonism. Methods in Enzymology. 2013;522:391-408.
[11] Liu X#, Sun H, Qi J, Wang L, He S, Liu J, Feng C, Chen C, Li W, Guo Y, Qin D, Pan G, Chen J, Pei D*, Zheng H*. Sequential introduction of reprogramming factors reveals a time-sensitive requirement for individual factors and a sequential EMT-MET mechanism for optimal reprogramming. Nature Cell Biology. 2013 Jul;15(7):829-38.?
[10] Zheng H*#, Zou H, Liu X, Chu J, Zhou Y, Loh HH, Law PY. Cholesterol level influences opioid signaling in cell models and analgesia in mice and humans. Journal of Lipid Research. 2012 Jun;53(6):1153-62.
[9] Zheng H*#, Pearsall EA, Hurst DP, Zhang Y, Chu J, Zhou Y, Reggio PH, Loh HH, Law PY. Palmitoylation and membrane cholesterol stabilize μ-opioid receptor homodimerization and G protein coupling. BMC Cell Biology. 2012 Mar 19;13:6. ???
[8] Zheng H*#, Law PY, Loh HH. Non-Coding RNAs Regulating Morphine Function: With Emphasis on the In vivo and In vitro Functions of miR-190. Frontiers in Genetics. 2012 Jun 15;3:113.
[7] Zheng H*#, Chu J, Zhang Y, Loh HH, Law PY. Modulating micro-opioid receptor phosphorylation switches agonist-dependent signaling as reflected in PKCepsilon activation and dendritic spine stability. The Journal of Biological Chemistry. 2011 Apr 8;286(14):12724-33.
[6] Zheng H*#, Zeng Y, Zhang X, Chu J, Loh HH, Law PY. mu-Opioid receptor agonists differentially regulate the expression of miR-190 and NeuroD. Molecular Pharmacology. 2010 Jan;77(1):102-9.
[5] Zheng H*#, Zeng Y, Chu J, Kam AY, Loh HH, Law PY. Modulations of NeuroD activity contribute to the differential effects of morphine and fentanyl on dendritic spine stability. Journal of Neuroscience. 2010 Jun 16;30(24):8102-10.
[4] Zheng H*#, Loh HH, Law PY. Agonist-selective signaling of G protein-coupled receptor: mechanisms and implications. IUBMB Life. 2010 Feb;62(2):112-9.
[3] Zheng H*#, Chu J, Zeng Y, Loh HH, Law PY. Yin Yang 1 phosphorylation contributes to the differential effects of mu-opioid receptor agonists on microRNA-190 expression. The Journal of Biological Chemistry. 2010 Jul 16;285(29):21994-2002.
[2] Zheng H*#, Loh HH, Law PY. Beta-arrestin-dependent mu-opioid receptor-activated extracellular signal-regulated kinases (ERKs) Translocate to Nucleus in Contrast to G protein-dependent ERK activation. Molecular Pharmacology. 2008 Jan;73(1):178-90.
[1] Zheng H*#, Chu J, Qiu Y, Loh HH, Law PY. Agonist-selective signaling is determined by the receptor location within the membrane domains. Proceedings of the National Academy of Sciences of the United States of America. 2008 Jul 8;105(27):9421-6.
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