科學(xué)研究:

研究方向:
主要從事表觀遺傳學(xué)調(diào)控基因表達(dá),腫瘤分子生物學(xué)(主要為p53方向)以及細(xì)胞自噬的研究。
承擔(dān)科研項目情況:
科技部973項目子課題“上皮間質(zhì)轉(zhuǎn)換的機理及腫瘤侵襲轉(zhuǎn)移的細(xì)胞重編程機制 ”。 科技部973項目子課題“DNA甲基化異常與腫瘤發(fā)生發(fā)展”。科技部973項目子課題“p53功能與修飾的研究”。國家自然科學(xué)基金委“國家杰出青年基金”項目:“組蛋白重塑誘導(dǎo)核苷衍生物導(dǎo)致的細(xì)胞凋亡的研究” 。國家自然科學(xué)基金委重點項目;“NuRD復(fù)合物協(xié)同作用PRC2復(fù)合物調(diào)控腫瘤發(fā)生的研究” 。
1、國家自然科學(xué)基金重大項目(2021-2025),DNA復(fù)制相關(guān)DNA代謝調(diào)控基因組穩(wěn)態(tài)的機制研究(32090030)。
2、國家自然科學(xué)基金重大項目課題(2021-2025),DNA同源重組及DNA雙鏈斷裂修復(fù)的分子機制研究(32090033) 。
3、深圳市科技計劃基礎(chǔ)研究重點項目(2020-2023),靶向NAD+合成通路調(diào)控 DNA損傷修復(fù)的抗腫瘤機制研究(JCYJ20200109114214463)。
4、深圳灣實驗室開放基金項目(2019-2022),細(xì)胞脅迫應(yīng)激與機體穩(wěn)態(tài)及疾病(SZBL2019062801011)。
5、國家重點研發(fā)計劃:“蛋白質(zhì)機器與生命過程調(diào)控”重點專項首席科學(xué)家,2017.07-2022.06。
6、國家重點研發(fā)計劃項目:參與DNA損傷應(yīng)答的新型蛋白質(zhì)機器維持基因組穩(wěn)定性的機制研究,項目編號:2017YFA0503900,2017-2022。
7、國際(地區(qū))合作與交流項目:組蛋白去乙酰化酶Sirtuin與p53相互調(diào)控的分子網(wǎng)絡(luò)及機制研究,項目編號:81720108027,2018.01-2021.12。
8、 基礎(chǔ)學(xué)科布局項目:基20170306 放療耐受性腫瘤的再致敏研究。
9、廣東省科技廳重點實驗室:廣東省基因組穩(wěn)定性與疾病防治重點實驗室!
10、國家基金委重點項目:組蛋白甲基轉(zhuǎn)移酶G9a參與腫瘤細(xì)胞脂代謝的機制研究 (No:81530074) ,負(fù)責(zé)人,2016-2-2020。
11、國家基金委創(chuàng)新團隊:蛋白質(zhì)翻譯后修飾與腫瘤發(fā)生發(fā)展及轉(zhuǎn)移的分子機制研究 (No:81321003),負(fù)責(zé)人,2014-2019。
12、國家基金委重大計劃重點項目:組蛋白去乙;窼IRT6招募NuRD復(fù)合物參與DNA損傷應(yīng)激的分子機制研究(No:91319302),負(fù)責(zé)人,2014-2016。
13、國家基金委重大計劃重點項目:pRB介導(dǎo)NuRD 復(fù)合物與H3K4去甲基化相互作用的機制研究 (No: 90919030),負(fù)責(zé)人,2009-2012。
14、國家“973”計劃研究項目子課題:DNA 甲基化變化在惡性腫瘤發(fā)生發(fā)展及侵襲轉(zhuǎn)移中的作用,負(fù)責(zé)人,2005-2010。
15、國家“973”計劃研究項目子課題:DNA甲基化異常與腫瘤發(fā)生發(fā)展。
16、國家“973”計劃研究項目子課題:蛋白質(zhì)生成、折疊、組裝和降解的規(guī)律及其質(zhì)量控制。
17、國家“863”計劃研究項目:(B類):腫瘤特異標(biāo)志物Pirh2磷酸化的鑒定及靶蛋白的設(shè)計與應(yīng)用,863計劃首席,2006。
18、國家自然基金委“杰出青年基金”腫瘤治療學(xué)基礎(chǔ) (No:30425017),2004。
19、國家杰出青年基金:染色質(zhì)重塑干擾核苷衍生物誘導(dǎo)的DNA損傷修復(fù)的機制研究,2004年。
主要學(xué)術(shù)成就:
主要從事腫瘤學(xué),生化與分子生物學(xué)的基礎(chǔ)研究。在腫瘤發(fā)生的機制研究和腫瘤的分子治療領(lǐng)域作出了較為突出的貢獻(xiàn)。在DNA甲基化導(dǎo)致腫瘤發(fā)生的基礎(chǔ)研究中,提出了“臨近位點阻礙說”對表觀遺傳導(dǎo)致基因失活的機理研究提出了新的理論,并發(fā)表在國際著名生物學(xué)雜志Mol Cell Biol上。在腫瘤的分子治療的機制研究中,建立了“核苷衍生物并用組蛋白乙;T導(dǎo)腫瘤細(xì)胞凋亡”的模型,受到國際該領(lǐng)域的重視和好評,并大量被引用。作者以該模型為研究中心, 相繼以第一作者或通訊作者身份發(fā)表了多篇高質(zhì)量的科學(xué)論文,分別發(fā)表在Cancer Research, Journal of Biological Chemistry, Oncogene, Human Molecular Genetics上。并且發(fā)現(xiàn)BMP3B基因為肺癌細(xì)胞中與甲基化相關(guān)聯(lián)的新的抑癌基因,并發(fā)表在Neoplasia 和 Oncogene等雜志上。在國際主流學(xué)術(shù)刊物如Nature, Nature Cell Biology, PNAS等發(fā)表了多篇論文,在腫瘤與生物醫(yī)學(xué)主要學(xué)術(shù)期刊上發(fā)表了70多篇SCI論文。2010年在Nature Cell Biology上首次論證了轉(zhuǎn)錄因子FOXO1在細(xì)胞漿內(nèi)的特異功能:誘導(dǎo)細(xì)胞自噬發(fā)生。2006,2008,2010年及2011年在Molecular &Cellular Biology, Journal of Biological Chemistry,Nature 和PNAS上闡述了腫瘤抑制因子p53的乙;揎椗c其功能的關(guān)系;2008年在Molecular &Cellular Biology上論證了組蛋白修飾可能參與指導(dǎo)DNA甲基化及基因表達(dá)的過程。
1. 發(fā)現(xiàn)在氧化應(yīng)激或饑餓時,轉(zhuǎn)錄因子FoxO1啟動腫瘤細(xì)胞自噬過程
該過程與III類組蛋白去乙;窼IRT2密切相關(guān)。腫瘤細(xì)胞在未處理的情況下,SIRT2與FoxO1相互作用使得FoxO1保持在去乙酰化狀態(tài)。但在各種應(yīng)激情況下,SIRT2與FoxO1脫開,使得FoxO1乙;,并結(jié)合到自噬的重要蛋白Atg7,從而啟動細(xì)胞自噬。該項研究將參與表觀遺傳的重要修飾酶的功能在應(yīng)激情況下與腫瘤細(xì)胞自噬有機的聯(lián)系起來,于2010年發(fā)表在《Nat Cell Biol》上。
2. 代謝相關(guān)的p53功能方面的研究
發(fā)現(xiàn)p53能夠下調(diào)在糖異生過程中兩種重要限速酶:磷酸烯醇型丙酮酸羧激酶(PCK1)和葡萄糖6-磷酸酶(G6PC) 的表達(dá)。細(xì)胞水平我們證實了p53能夠引起叉頭框轉(zhuǎn)錄因子(FOXO1)的核輸出,而FOXO1正是PCK1和G6PC的轉(zhuǎn)錄激活因子。因而p53能夠抑制FOXO1依賴性的糖異生。進(jìn)一步的研究表明, p53可以直接激活NAD(+)依賴的組蛋白去乙酰化酶Sirtuin 6(SIRT6)的表達(dá)。SIRT6與FoxO1的相互作用會引起FoxO1的去乙酰進(jìn)而引起FOXO1轉(zhuǎn)位到胞漿。C57Bl/J6小鼠以及肝臟條件性敲除SIRT6的小鼠也證實了p53介導(dǎo)的FOXO1出核,下調(diào)PCK1和G6PC進(jìn)而調(diào)節(jié)血糖的實驗結(jié)果。該工作2014年發(fā)表在《PNAS》上。
3. DNA損傷應(yīng)答的研究
腫瘤細(xì)胞在化療藥物阿霉素處理后,組蛋白甲基化酶SET7/9與另一個組蛋白甲基化酶SUV39H1相互作用, 并導(dǎo)致SUV39H1甲基化。甲基化的SUV39H1活性明顯下降,從而使異染色質(zhì)結(jié)構(gòu)變得松散,DNA易于碎裂。該項研究成果部分解釋了抗癌化療的機制并有機地與表觀遺傳的分子機制有效聯(lián)系起來。該工作2013年發(fā)表在《PNAS》上。
4. 發(fā)現(xiàn)SET7/9調(diào)節(jié)組蛋白去乙酰化酶SIRT1對p53乙;绊憄53功能
DNA損傷后,SET7/9和SIRT1相互作用顯著增強,SET7/9對p53進(jìn)行甲基化修飾同時抑制了SIRT1對p53的作用,提高了p53乙;。SET7/9不僅可以直接對p53進(jìn)行甲基化修飾,還作為一個關(guān)鍵調(diào)節(jié)分子,通過調(diào)節(jié)SIRT1-p53相互作用,從而間接調(diào)節(jié)p53功能。該工作2011年發(fā)表在《PNAS》上。
科研成果:
1. 組蛋白去乙;敢种苿┮种颇[瘤細(xì)胞增殖的機制研究 朱衛(wèi)國; 趙穎; 王海英; 楊洋; 于宇; 廖文娟; 馮京南; 王麗娜 【科技成果】北京大學(xué)基礎(chǔ)醫(yī)學(xué)院 2009-06-01
2. 組蛋白去乙;傅淖饔脵C制 朱衛(wèi)國 第五屆“藥明康德生命化學(xué)研究獎”。
發(fā)明專利:
[1]程永現(xiàn), 朱衛(wèi)國, 晏永明, 康天舒, 谷金科, 陸小鵬. 一種小分子化合物及其制備方法與應(yīng)用[P]. 廣東省: CN117623929A, 2024-03-01.
[2]朱衛(wèi)國, 程永現(xiàn), 康天舒, 晏永明, 陸小鵬, 黃金波. 一種小分子化合物YZL-51N在制備SIRT7選擇性抑制劑中的應(yīng)用[P]. 廣東省: CN117357507A, 2024-01-09.
[3]朱衛(wèi)國. 一種高通量大規(guī)模篩選組蛋白修飾結(jié)合蛋白質(zhì)的方法[P]. 廣東省: CN113588856B, 2023-07-21.
[4]康天舒, 朱衛(wèi)國, 賀靜. 一種檢測SIRT7酶活性的熒光多肽底物[P]. 廣東省: CN113880922B, 2023-06-13.
[5]朱衛(wèi)國, 黃金波, 張俊, 許文超. 組蛋白去乙;8選擇性降解劑、制備方法及其在抗腫瘤活性中的應(yīng)用[P]. 廣東省: CN114409638B, 2023-02-14.
[6]文赫, 朱衛(wèi)國, 劉向宇. 一種評價組蛋白賴氨酸去甲基轉(zhuǎn)移酶活性的方法[P]. 廣東省: CN109825551B, 2022-08-02.
[7]文赫, 朱衛(wèi)國, 李曉帆, 田媛, 王慧. 基于核磁共振氫譜的LSD1的活性檢測方法及其應(yīng)用[P]. 廣東省: CN112098448B, 2022-05-20.
[8]朱衛(wèi)國, 黃金波, 張俊, 許文超. 組蛋白去乙酰化酶8選擇性降解劑、制備方法及其在抗腫瘤活性中的應(yīng)用[P]. 廣東省: CN114409638A, 2022-04-29.
[9]文赫, 朱衛(wèi)國, 舒明慧, 陳嘉儀, 李曉帆. 基于一維HNCO核磁共振光譜檢測SIRTs去乙;富钚缘姆椒皯(yīng)用[P]. 廣東省: CN114414608A, 2022-04-29.
[10]朱衛(wèi)國, 黃金波, 吳丹丹, 白曉康. 一種3-多氟烷基化取代咪唑[1,2-a]并吡啶的簡易合成方法[P]. 廣東省: CN112851670B, 2022-01-04.
[11]康天舒, 朱衛(wèi)國, 賀靜. 一種檢測SIRT7酶活性的熒光多肽底物[P]. 廣東省: CN113880922A, 2022-01-04.
[12]朱衛(wèi)國. 一種高通量大規(guī)模篩選組蛋白修飾結(jié)合蛋白質(zhì)的方法[P]. 廣東省: CN113588856A, 2021-11-02.
[13]朱衛(wèi)國, 黃金波, 吳丹丹, 白曉康. 一種3-多氟烷基化取代咪唑[1,2-a]并吡啶的簡易合成方法[P]. 廣東省: CN112851670A, 2021-05-28.
[14]文赫, 朱衛(wèi)國, 李曉帆, 田媛, 王慧. 基于核磁共振氫譜的LSD1的活性檢測方法及其應(yīng)用[P]. 廣東省: CN112098448A, 2020-12-18.
[16]文赫, 朱衛(wèi)國, 劉向宇. 一種評價組蛋白賴氨酸去甲基轉(zhuǎn)移酶活性的方法[P]. 廣東省: CN109825551A, 2019-05-31.
論文專著:

在國內(nèi)外重要雜志上發(fā)表50余篇文章。
出版專著:
1. DNA REPLICATION- Damage and Replication stress responses. 沈萍 王海英 朱衛(wèi)國
2.論著名稱:“分子細(xì)胞生物學(xué)”第3版,第二章“表觀遺傳調(diào)控部分”,朱衛(wèi)國、文赫、朱騫,高等教育出版社,2019年8月。
3. 論著名稱:“承續(xù)的魅力:令人著迷的表觀遺傳學(xué)”第1版,第一章“組蛋白修飾”部分,朱衛(wèi)國、文赫、朱騫,科學(xué)出版社,2018年11月。
發(fā)表英文論文: 帶*號的為責(zé)任作者
1. Zhu Q, Yang Q, Lu X, Wang H, Tong L, Li Z, Liu G, Bao Y, Xu X, Gu L, Yuan J, Zhu WG*. SETD2-mediated H3K14 trimethylation promotes ATR activation and stalled replication fork restart in response to DNA replication stress. Proc Natl Acad Sci USA. 2021, 118(23):e2011278118. doi: 10.1073/pnas.2011278118.
2. Hou T, Cao Z, Zhang J, Tang M, Tian Y, Li Y, Lu X, Chen Y, Wang H, Wei FZ, Wang L, Yang Y, Zhao Y, Wang Z, Wang H, Zhu WG*. SIRT6 coordinates with CHD4 to promote chromatin relaxation and DNA repair.Nucleic Acids Res. 2020, 48(6):2982-3000.
3. Tang M, Li Z, Zhang C, Lu X, Tu B, Cao Z, Li Y, Chen Y, JInag L, Wang H, Wang L, Wang J, Liu B, Xu X, Wang H, Zhu WG*. SIRT7-mediated ATM deacetylation is essential for its deactivation and DNA damage repair. Science Advances., 2019, 5: eaav 1118.
4. Li Z, Li Y, Tang M, Peng B, Lu X, Yang Q, Zhu Q, Hou T, Li M, Liu C, Wang L, Xu X, Zhao Y, Wang H, Yang Y, Zhu WG*. Destabilization of linker histone H1.2 is essential for ATM activation and DNA damage repair.Cell Res. 2018, 28(7):756-770.
5.Yang Q, Zhu Q, Lu X, Du Y, Cao L, Shen C, Hou T, Li M, Li Z, Liu C, Wu D, Xu X, Wang L, Wang H, Zhao Y, Yang Y, Zhu WG*. (2017) G9a coordinates with the RPA complex to promote DNA damage repair and cell survival. Proc Natl Acad Sci USA. 2017,114(30):E6054-E6063.
6. Cao LL, Wei F, Du Y, Song B, Wang D, Shen C, Lu X, Cao Z, Yang Q, Gao Y, Wang L, Zhao Y, Wang H, Yang Y, Zhu WG* (2016). ATM-mediated KDM2A phosphorylation is required for the DNA damage repair. Oncogene 35(3): 402.
7. Wang Y, Zhang N, Zhang L, Li R, Fu W, Ma K, Li X, Wang L, Wang J, Zhang H, Gu W, Zhu WG*, Zhao Y*. Autophagy Regulates Chromatin Ubiquitination in DNA Damage Response through Elimination of SQSTM1/p62. Mol Cell. 2016, 63(1):34-48.
8. Wei FZ, Cao Z, Wang X, Wang H, Cai MY, Li T, Hattori N, Wang D, Du Y, Song B, Cao LL, Shen C, Wang L, Wang H, Yang Y, Xie D, Wang F, Ushijima T, Zhao Y*, Zhu WG*. Epigenetic regulation of autophagy by the methyltransferase EZH2 through an MTOR-dependent pathway. Autophagy. 2015 Nov;11(12):2309-22. doi: 10.1080/15548627.2015.1117734.
9. Cao LL, Wei F, Du Y, Song B, Wang D, Shen C, Lu X, Cao Z, Yang Q, Gao Y, Wang L, Zhao Y, Wang H, Yang Y, Zhu WG*. ATM-mediated KDM2A phosphorylation is requiredfor the DNA damage repair. Oncogene. 2015 Mar 30. doi: 10.1038/onc.2015.81. [Epubahead of print]
10.Wu D, Liu J, Wu B, Tu B, Zhu WG, Luo J. The Batten disease gene CLN3 confers resistance to endoplasmic reticulum stress induced by tunicamycin. Biochemical and Biophysical Research Communications [Internet]. 2014;(1):115-120.
11. Wang Y, Qiu B, Liu J, Zhu WG, Zhu S. Cocaine- and amphetamine-regulated transcript facilitates the neurite outgrowth in cortical neurons after oxygen and glucose deprivation through PTN-dependent pathway. Neuroscience. 2014 Sep 26;277:103-10.
12. Yi J, Huang X, Yang Y, Zhu WG, Gu W, Luo J. Regulation of histone acetyltransferase TIP60 function by histone deacetylase 3.J Biol Chem. 2014 Oct 9. pii: jbc.M114.575266.
13. Li T, Song B, Wu Z, Lu M, Zhu WG*. Systematic identification of Class I HDAC substrates. Brief Bioinform. 2014 Nov;15(6):963-972.
14.Yao Y, Yang Y, Zhu WG*.Sirtuins: Nodes connecting aging, metabolism and tumorigenesis. Current Pharmaceutical Design. 2014,20(11):1614-1624.
15.Li Z, Zhu WG*. Targeting histone deacetylases for cancer therapy: From molecular mechanisms to clinical implications. International Journal of Biological Sciences. 2014;(7):757-770.
16.Zhang P, Tu B, Wang H, Cao Z, Tang M, Zhang C, Gu B, Li Z, Wang L, Yang Y, Zhao Y, Wang H, Luo J, Deng CX, Gao B, Roeder RG, Zhu WG*. Tumor suppressor p53 cooperates with SIRT6 to regulate gluconeogenesis by promoting FoxO1 nuclear exclusion. Proceedings of the National Academy of Sciences of the United States of America [Internet]. 2014;111(29):10684-10689.
17.Li L, Zhang Z-G, Lei H, Wang C, Wu L-P, Wang J-Y, Fu F-Y, Zhu W-G, Wu L-L. Angiotensin II Reduces Cardiac AdipoR1 Expression through AT1 Receptor/ROS/ERK1/2/c-Myc Pathway. PLoS ONE [Internet]. 2013;(1).
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發(fā)表中文期刊論文:
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