杜丹

研究领域：

    哺乳动物细胞中基因间的遗传学相互作用，是多个基因协同调控机体发育、应激应答、疾病发生发展、及癌症治疗耐受的分子基础。比如基因之间存在代偿作用（如头颈口腔癌放化疗耐受）或者多基因协同调控生物学过程（如颅面发育、细胞去分化或转分化）。

主要研究方向：

        1. 运用CRISPRn/i/a（敲出、抑制或激活靶基因）技术，结合相应的全基因组文库或功能性亚库，在不同类型头颈（口腔）肿瘤，不同遗传学背景下，筛选调控肿瘤细胞对不同抗肿瘤药物或放疗耐受的基因。

       2. 完善基于shRNA和CRISPRn/i/a技术平台，构建同时敲出、干扰或激活多个基因表达的文库，运用高通量的遗传学筛选方法，结合深度测序技术，研究基因间的遗传互作。

       3. 肿瘤细胞的极性状态、干性状态、代谢状态、药物敏感性和射线敏感性之间紧密相关，但其中的分子联系基础并不清楚。运用高通量研究遗传互作的平台，研究这些基因群之间的功能性相互作用及机制。

       4. 肿瘤微环境通过影响细胞内基因的遗传互作，从而调控肿瘤细胞产生放疗、化疗、靶向治疗耐受和免疫治疗抑制。口腔微环境中微生物、间充质细胞、免疫细胞和上皮细胞相互作用机制并不清楚。运用高通量研究遗传互作的平台，研究口腔微环境和上皮细胞相互作用的机制。

学习经历：

1998~2002 南京大学生物化学系生物化学专业,理学学士；

2002~2009 中国科学院上海生化细胞所生物化学和分子生物学专业,理学博士；

2005.3~2005.12 德国马克思普朗克生物化学研究所,访问博士；

2006.1~2006.4 丹麦哥本哈根分子病理研究所，访问博士；

工作经历：

2009~2010 中国科学院上海生化细胞所  研究助理；

2010~2015 美国加州大学旧金山分校牙学院细胞和组织学系博士后；

2015~2018 美国加州大学旧金山分校牙学院细胞和组织学系副研究专家；

2014.10~2015.3美国斯坦福大学生物工程学系访问学者；

2015.5~2017.4美国格拉德斯通研究所访问学者；

代表性成果：

1. Dan Du#, Yoko Katsuno, Dominique Meyer, Erine H. Budi, Si-Han Chen, Hongjun Wang, Hartmut Koeppen, Rosemary Akhurst, Rik Derynck#. Smad3‐mediated recruitment of the methyltransferase SETDB1/ESET controls Snail1 expression and epithelial–mesenchymal transition.  EMBO Reports., 2017 Dec 12th; 19(1), 135-155 (#: co-corresponding author);

2. Dan Du*, Assen, Roguev*, David E Gordon，Meng Chen, Si-Han Chen, John Paul Shen, Prashant Mali, Trey Ideker, Stanley Qi, Nevan Krogan. Genetic interaction mapping in mammalian cells using CRISPR interference. Nat. Methods., 2017 May 8th; 14(6), 577–580 (*: co-first author)；

3. Dan Du, Feilai Xu, Lihou Yu, Chenyi Zhang, Xuefeng Lu, Haixin Yuan, Qin Huang, Fan Zhang, Xunwei Wu, Zhe Zhang, Xueliang Zhu, Xiaohui Zhang, Zhengjun Chen. Tight junction protein occludin regulates directional migration of epithelial cells. Dev Cell., 2010 Jan 19th, 18 (1), 52-63；

4. Dan Du, Stanley Qi. CRISPR Technology for Genome Activation and Repression in Mammalian Cells. Cold Spring Harb Protoc. 2016 Jan 4th; (1), pdb. prot090175；

5. Dan Du, Stanley Qi. An Introduction to CRISPR Technology for Genome Activation and Repression in Mammalian Cells. Cold Spring Harb Protoc. 2016 Jan 4th ; (1), pdb. top086835；

6. Dan Du, Esben Pedersen, Zhipeng Wang, Richard Karlsson, Zhengjun Chen, Xunwei Wu, Cord Brakebusch. (2009) Cdc42 is crucial for the maturation of primordial cell junctions in keratinocytes independent of Rac1. Exp Cell Res., 315, 1480-1489.

主持过的重要课题：

1. 国家自然科学基金面上项目（81972823，KMT1E-s在乳腺癌治疗耐受和复发中的功能及机制研究，2020-2023，60万元）

2. 闽江学者启动经费（200万元）

3. Human Frontier Science Program (HFSP) fellowship (as PI), “Role of the methyltransferase ESET in TGF-beta signaling and EMT”, 2011-2014. This award is around $160,980.

所有论文列表：

1. Li Zhong, Ying Xu, Ren-Gong Zhuo, Tingting Wang, Kai Wang, Ruizhi Huang, Daxin Wang, Yue Gao, Yifei Zhu, Xuan Sheng, Kai Chen, Na Wang, Lin Zhu, Dan Can, Yuka Martens, Mitsuru Shinohara, Chia-Chen Liu, Dan Du, Hao Sun, Lei Wen, Huaxi Xu, Guojun Bu, and Xiaofen chen. Soluble TREM2 ameliorates pathological phenotypes by modulating microglial functions in a mouse model of Alzheimer’s disease. Nature Communications., 2019 in press

2. Si‐Han Chen, Gwendolyn M Jang, Ruth Hüttenhain, David E Gordon, Dan Du, Billy W Newton, Jeffrey R Johnson, Joseph Hiatt, Judd F Hultquist, Tasha L Johnson, Yi‐Liang Liu, Lily A Burton, Jordan Ye, Kurt M Reichermeier, Robert M Stroud, Alexander Marson, Jayanta Debnath, John D Gross, Nevan J Krogan#. CRL4AMBRA1 targets Elongin C for ubiquitination and degradation to modulate CRL5 signaling. EMBO J., 2018 Aug 30th ,doi:10.15252/embj.201797508

3. Dan Du#, Yoko Katsuno, Dominique Meyer, Erine H. Budi, Si-Han Chen, Hongjun Wang, Hartmut Koeppen, Rosemary Akhurst, Rik Derynck#. Smad3‐mediated recruitment of the methyltransferase SETDB1/ESET controls Snail1 expression and epithelial–mesenchymal transition.  EMBO Reports., 2017 Dec 12th; 19(1), 135-155 (#: co-corresponding author). doi: 10.15252/embr.201744250

4. Dan Du*, Assen, Roguev*, David E Gordon，Meng Chen, Si-Han Chen, John Paul Shen, Prashant Mali, Trey Ideker, Stanley Qi, Nevan Krogan. Genetic interaction mapping in mammalian cells using CRISPR interference. Nat. Methods., 2017 May 8th; 14(6), 577–580 (*: co-first author). doi:10.1038/nmeth.4286

5. John Paul Shen, Dongxin Zhao, Roman Sasik, Jens Luebeck, Amanda Birmingham, Ana Bojorquez-Gomez, Katherine Licon, Kristin Klepper, Daniel Pekin, Alex N Beckett, Kyle Salinas Sanchez, Alex Thomas, Chih-Chung Kuo, Dan Du, Assen Roguev, Nathan E Lewis, Aaron N Chang, Jason F Kreisberg, Nevan Krogan, Lei Qi, Trey Ideker, Prashant Mali. Combinatorial CRISPR–Cas9 screens for de novo mapping of genetic interactions. Nat. Methods., 2017 May 8th; 14(6), 573–576. doi:10.1038/nmeth.4225

6. Dan Du, Stanley Qi. CRISPR Technology for Genome Activation and Repression in Mammalian Cells. Cold Spring Harb Protoc. 2016 Jan 4th; (1), pdb. prot090175. doi:10.1101/pdb.prot090 175.

7. Dan Du, Stanley Qi. An Introduction to CRISPR Technology for Genome Activation and Repression in Mammalian Cells. Cold Spring Harb Protoc. 2016 Jan 4th ; (1), pdb. top086835. doi:10.1101/pdb.top086835

8. Pinglong Xu, Samantha Bailey-Bucktrout, Ying Xi, Daqi Xu, Dan Du, Qian Zhang, Weiwen Xiang, Jianming Liu, Andrew Melton, Dean Sheppard, Harold A. Chapman, Jeffrey A. Bluestone, Rik Derynck. Innate Antiviral Host Defense Attenuates TGF-β Function through IRF3-Mediated Suppression of Smad Signaling. Mol Cell., 2014 Dec 18th;56(6), 723–737. doi: https://doi.org/ 10.1016/j.molcel.2014.11.027

9. Dan Du, Feilai Xu, Lihou Yu, Chenyi Zhang, Xuefeng Lu, Haixin Yuan, Qin Huang, Fan Zhang, Xunwei Wu, Zhe Zhang, Xueliang Zhu, Xiaohui Zhang, Zhengjun Chen. Tight junction protein occludin regulates directional migration of epithelial cells. Dev Cell., 2010 Jan 19th, 18 (1), 52-63. doi: https://doi.org/10.1016/j.devcel.2009.12.008

10. Dan Du, Esben Pedersen, Zhipeng Wang, Richard Karlsson, Zhengjun Chen, Xunwei Wu, Cord Brakebusch. (2009) Cdc42 is crucial for the maturation of primordial cell junctions in keratinocytes independent of Rac1. Exp Cell Res., 315, 1480-1489. (doi:10.1016/j. yexcr .2008.11.012.)

11. Xuefeng Lu*, Xiujing Feng*, Xiaobo Man, Guang Yang, Liang Tang, Dan Du, Fan Zhang, Haixin Yuan, Qin Huang, Zhe Zhang, Yinkun Liu, Dennis Strand, Zhengjun Chen. (2009) Aberrant Splicing of Hugl-1, the Human Homologue of Drosophila Tumor Suppressor Gene lgl, is Associated with Hepatocellular Carcinoma Progression. Clin Cancer Res., 15(10), 3287-3296 (*: co-first author)

12. Haixin Yuan*, Hong Zhang*, Xunwei Wu, Zhe Zhang, Dan Du, Wenchao Zhou, Shuhua Zhou, Cord Brakebusch, Zhengjun Chen. (2009) Hepatocyte-Specific Deletion of Cdc42 Results in Delayed Liver Regeneration after Partial Hepatectomy in Mice. Hepatology., 49,240-249. (*: co-first author)

13. Zhou Ying*, Fang Longhou*, Du Dan, Zhou Wenchao, Feng Xiujing, Chen Jiwu, Chen Zhengjun. (2008) Proteome identification of binding-partners interacting with cell polarity protein Par3 in Jurkat cells. Acta Biochim Biophys Sin (Shanghai)., 8:729-39. (*: co-first author)

14. Longhou Fang, YiGuo Wang, Dan Du, Guang Yang, Tim Tak Kwok, Siu Kai Kong, Benjamin Chen, David J. Chen, and Zhengjun Chen. (2007) Cell polarity protein Par3 complexes with DNA-PK via Ku70 and regulates DNA double-strand break repair. Cell Res., 17: 100-116.

15. YiGuo Wang, Dan Du, Longhou Fang, Guang Yang, Chenyi Zhang, F Lottspeich, Axel Ullrich, Zhengjun Chen. (2006) Tyrosine Phosphorylated Par3 Regulates Epithelial Tight Junction Assembly Promoted by EGFR Signaling. EMBO J., 5:5058-5070

16. YiGuo Wang*, Rongxia Li*, Dan Du, Chenyi Zhang, Haixin Yuan, Rong Zeng, and Zhengjun Chen. (2006) Proteomic Analysis Reveals Novel Molecules Involved in Insulin Signaling Pathway. J Proteome. Res., 5:846-855 (*: co-first author).