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張文翔

后天免疫轉(zhuǎn)錄調(diào)控

電話：18201743056

郵箱：[email protected]

基因的轉(zhuǎn)錄調(diào)控機(jī)制是生命科學(xué)中的基礎(chǔ)問(wèn)題，涉及精細(xì)的分子層面和細(xì)胞網(wǎng)絡(luò)調(diào)控,。圍繞后天免疫轉(zhuǎn)錄調(diào)控,，課題組研究發(fā)現(xiàn)：基因組中重復(fù)微衛(wèi)星序列與轉(zhuǎn)錄因子相互作用，形成啟動(dòng)子-增強(qiáng)子環(huán),，提出新的基因轉(zhuǎn)錄調(diào)控模型(Nature, 2023）；轉(zhuǎn)錄因子FOXP3在Treg細(xì)胞功能中的多樣化調(diào)控機(jī)制，糾正了過(guò)去10多年的誤區(qū)(Immunity, 2022）,。課題組將從分子和生化的角度深入研究適應(yīng)性免疫中基因的轉(zhuǎn)錄調(diào)控機(jī)制，為腫瘤治療和自身免疫疾病提供治療策略,。

課題組將以已有的研究成果為基礎(chǔ),，致力于解決腫瘤發(fā)生和免疫調(diào)節(jié)中的關(guān)鍵問(wèn)題。依托上海交通大學(xué)醫(yī)學(xué)院,、上海市免疫學(xué)研究所和瑞金醫(yī)院的科研和臨床資源,，計(jì)劃從分子和生化的角度，多學(xué)科交叉,、并開(kāi)發(fā)多種研究和分析方法,，深入探索基因的轉(zhuǎn)錄調(diào)控機(jī)制，并尋求臨床轉(zhuǎn)化：

1） 進(jìn)一步探究轉(zhuǎn)錄因子FOXP3在Treg細(xì)胞調(diào)控的分子機(jī)制,，及其在腫瘤微環(huán)境和自身免疫疾病中的動(dòng)態(tài)調(diào)控機(jī)制,。

2） 研究整個(gè)免疫系統(tǒng)中其他核心轉(zhuǎn)錄因子的調(diào)控機(jī)制，探索未知的更為復(fù)雜的調(diào)控模式,，致力于發(fā)現(xiàn)普適性機(jī)制,。

3） 基因組中Microsatellite微衛(wèi)星序列在免疫調(diào)節(jié)和基因組穩(wěn)定性中的作用，探討其與特定疾病的關(guān)聯(lián)性,，并結(jié)合流行病學(xué)進(jìn)行分析,。

實(shí)驗(yàn)室主頁(yè)：http://dripwizz.com/sii/info/1053/3801.htm

張文翔研究員2018年1月于中科院上海生物化學(xué)與細(xì)胞生物學(xué)研究所 (現(xiàn)為分子細(xì)胞科學(xué)卓越創(chuàng)新中心) 獲博士學(xué)位。經(jīng)歷工業(yè)界和投資界實(shí)踐后,，2019年9月加入哈佛醫(yī)學(xué)院/HHMI Sun Hur實(shí)驗(yàn)室擔(dān)任博士后/講師,，2024年4月回國(guó)成立“后天免疫轉(zhuǎn)錄調(diào)控”課題組。課題組立志在基礎(chǔ)研究的同時(shí)緊密結(jié)合臨床實(shí)踐,，并探索臨床轉(zhuǎn)化,。致力于在解決科學(xué)問(wèn)題的同時(shí)，滿足臨床需求，期望能夠研發(fā)出原創(chuàng)性藥物,，惠及廣大患者,。力求在生物醫(yī)藥領(lǐng)域取得突破性的成果，為人類的健康事業(yè)貢獻(xiàn)力量,。

在生物化學(xué),、細(xì)胞生物學(xué)、免疫生物學(xué),、藥物研發(fā),、遺傳學(xué)、結(jié)構(gòu)生物學(xué)和生物信息學(xué)等多個(gè)領(lǐng)域接受系統(tǒng)且深入的訓(xùn)練,，相關(guān)研究成果發(fā)表于Nature, Immunity (封面), Nat. Commun, J Biol Chem等期刊,，被Nature, Immunity, Elite News, Chemical Word等權(quán)威媒介專題報(bào)道，擔(dān)任Nature Immunology,，Frontiers in Immunology等期刊的審稿人,，并獲Jeffery Modell獎(jiǎng)和余?學(xué)者等。此外,，具有工業(yè)界藥物研發(fā)（曾擔(dān)任醫(yī)藥公司科學(xué)家）和生物醫(yī)藥早期風(fēng)險(xiǎn)投資（曾擔(dān)任風(fēng)投公司投資經(jīng)理）的豐富經(jīng)驗(yàn),，并作為創(chuàng)始人獲得風(fēng)險(xiǎn)投資成功將生物創(chuàng)新項(xiàng)目落地。這種跨學(xué)術(shù)界,、工業(yè)界和投資界的多元化經(jīng)歷,，促進(jìn)了對(duì)生物醫(yī)藥行業(yè)更加全面和深刻的理解。

1,、上海交通大學(xué)醫(yī)學(xué)院引進(jìn)人才啟動(dòng)基金,，2024-2030，300萬(wàn)元,，課題負(fù)責(zé)人

2,、上海市免疫學(xué)研究所引進(jìn)人才啟動(dòng)基金，2024-2030,，300萬(wàn)元,，課題負(fù)責(zé)人

1. Wenxiang Zhang*, Fangwei Leng*, Xi Wang, Ricardo N. Ramirez, Jinseok Park, Christophe Benoist and Sun Hur. FOXP3 recognizes microsatellites and bridges DNA through multimerization[J]. Nature, 624 (7991),433-441.

Doi: https://www.nature.com/articles/s41586-023-06793-z

·Highlighted in News & Views in the same issue of Nature.

·Featured in the Innovation, Elite News, Chemical Word and Evolution News & Science Today.

2. Fangwei Leng*, Wenxiang Zhang*, Ricardo N. Ramirez, Juliette Leon, Yi Zhong, Lifei Hou, Koichi Yuki, Joris van der Veeken, Alexander Y Rudensky, Christophe Benoist, Sun Hur. The transcription factor FoxP3 can fold into two dimerization states with divergent implications for regulatory T cell function and immune homeostasis [J]. Immunity, 2022, 55(8): 1354-1369. (*, equal contribution).

Doi: https://doi.org/10.1016/j.immuni.2022.07.002

·Highlighted in Preview in the same issue of Immunity and selected as Cover Article.

3. Juliette Leon, Kaitavjeet Chowdhary, Wenxiang Zhang, Ricardo N. Ramirez, Isabelle André, Sun Hur, Diane Mathis, and Christophe Benoist. Mutations from patients with IPEX ported to mice reveal different patterns of FoxP3 and Treg dysfunction[J]. Cell Reports, 2023, 42(8).

4. Wenxiang Zhang, Jinjin Xu, Jinhui Li, Tong Guo, et al, Lei Zhang. The TEA domain family transcription factor TEAD4 represses murine adipogenesis by recruiting cofactors VGLL4 and CtBP2 into a transcriptional complex. Journal of Biological Chemistry, 2018: jbc. RA118. 003608.

5. Chao Wang*, Wenxiang Zhang*, Meng-Xin Yin, Lianxin Hu, et al, Lei Zhang. Suppressor of Deltex mediates Pez degradation and modulates Drosophila midgut homeostasis. Nature Communications 2015, 6:6607. (*, equal contribution)

6. Lingli He, Liang Yuan, Yang Sun, Pingyang Wang, Xue Feng, Zuoyun Wang, Wenxiang Zhang, et al, Lei Zhang. Glucocorticoid receptor signaling activates TEAD4 to promote breast cancer progression[J]. Cancer research, 2019, 79(17): 4399-4411.

7. Xue Feng, Zuoyun Wang, Fei Wang, Tiantian Lu, Jinjin Xu, Jinhui Li, Lingli He, Wenxiang Zhang, et al, Lei Zhang. Dual function of VGLL 4 in muscle regeneration[J]. The EMBO journal, 2019, 38(17): e101051.

8. Lingli He, Liang Yuan, Wentao Yu, Yang Sun, Dan Jiang, Xiaodong Wang, Xue Feng, Zuoyun Wang, Jinjin Xu, Ruizeng Yang, Wenxiang Zhang, et al, Lei Zhang. A regulation loop between YAP and NR4A1 balances cell proliferation and apoptosis[J]. Cell Reports, 2020, 33(3): 108284.

9. Lingli He, Wentao Yu, Wenxiang Zhang, Lei Zhang. An optimized two-step chromatin immunoprecipitation protocol to quantify the associations of two separate proteins and their common target DNA[J]. STAR protocols, 2021, 2(2): 100504.

10. Lingli He, Wentao Yu, Yi Lu, Wenxiang Zhang, Jinjin Xu, Lei Zhang. A protocol for in vivo analysis of liver tumorigenesis in mice using sleeping beauty transposon system[J]. STAR protocols, 2021, 2(2): 100445.

11. Chao Wang, Wenxiang Zhang, Meng-Xin Yin, Lei Zhang. The Study on the Regulatory Mechanisms of Drosophila Midgut Homeostasis by Hippo Signaling. Chinese Journal of Cell Biology 2015, 37(5): 599–603.