Fei Lan, Ph.D.

Education

• 2002-2008, Ph.D., Cell and Developmental Biology, Harvard University

• 1999-2002, M.S., Fudan University, Shanghai Medical School

• 1995-1999, B.S., Fudan University, School of Life Sciences

Working experience

• 2013-now, PI, Professor, Fudan University,

• 2019- Now Vice Dean of Research, Institutes of Biomedical Sciences

• 2017-Now Co-Director, Shanghai Key Laboratory of Medical Epigenetics

• 1/2012-12/2012, Senior Scientist I at Constellation Pharmaceuticals

• 1/2009-12/2011, Scientist II at Constellation Pharmaceuticals

• 02/2008-12/2008, Scientist I at Constellation Pharmaceuticals

Contact

Institutes of Biomedical Sciences, Fudan University, Shanghai 200032

Tel: +86-21-54237875

Email: fei_lan@fudan.edu.cn

Biography

I have more than 20 years of experience in epigenetics research, especially the dynamic regulation of lysine methylation. From 2004 to 2007, I made major contribution to the discovery of several families of histone demethylases, and the first PHD reader of unmodified lysine in histone H3 tail region. These findings lay out the foundation of the demethylation research area.

From 2008 to 2012, I spent 5 years in a startup biotech, called Constellation Pharmaceutics, to develop epigenetics drugs to cure diseases. I joined the company as the founding scientist and established the first drug discovery platform of histone demethylases. Two projects that I was involved are now in FDA Clinical Phase II-III aiming to treat myelofibrosis and advanced solid and hematologic cancers.

By the end 2012, I return to Fudan University and established my own research group studying the functional importance of various lysine methylations. My current research interests are in two major areas, including 1) epigenetic mis-regulation in cancer and other diseases; 2) the biology of lysine methylation beyond chromatin. In the past few years, my group discovered overactivated state of enhancer and connected such state to tumorigenesis, and identified several new methyl marks in key factors regulating protein translation and cell fate decision. These researches also provide key evidences of potential drug targets in treating diseases.

Research Areas

• Epigenetics, transcription, and chromatin

• Protein translation regulation

• Cancer biology

Awards and Honors

2019   The National Science Fund for Distinguished Young Scholars

2016   Tan Price (Innovation)

2012   Thousand Youth Talents

2007  Profiled in Harvard Medical School Dean’s Report 2007 as THE representative of all Ph.D. students in BBS program of Harvard Medical School

1999   Magna cum Laude, Fudan University

Selected Publications

1. Xu W, He C, Kaye EG, Li J, Mu M, Nelson GM, Dong L, Wang J, Wu F, Shi YG, Adelman K*, Lan F*, Shi Y*, Shen H*. Dynamic control of chromatin-associated m 6 A methylation regulates nascent RNA synthesis. Mol Cell. 2022 Mar 17;82(6):1156-1168

2. He C, Lan F*.  RNA m 6 A meets transposable elements and chromatin Protein & Cell, 2021 Dec; 12(12):906-910

3. Xu S, Wang S, Xing S, Yu D, Rong B, Gao H, Sheng M, Tan Y, Sun X, Wang K, Xue K, Shi Z*, Lan F*. KDM5A suppresses PML-RARα target gene expression and APL differentiation through repressing H3K4me2. Blood Adv. 2021 Sep 14;5(17):3241-3253.

4. Niu, C., Wang, S., Guo, J., Wei, X., Jia, M., Chen, Z., Gong, W., Qin, Y., Wang, X., Zhi, X., Lu, M., Chen, S., Gu, M., Zhang, J., Han, J.-D. J., Lan, F.*, and Meng, D*. BACH1 recruits NANOG and histone H3 lysine 4 methyltransferase MLL/SET1 complexes to regulate enhancer–promoter activity and maintains pluripotency. Nucleic Acids Research 2021 https://doi.org/10.1093/nar/gkab03 (* Correspondence)

5. Rong B, Zhang Q, Wan J, Xing S, Dai R, Li Y, Cai J, Xie J, Song Y, Chen J, Zhang L, Yan G, Zhang W, Gao H, Han JJ, Qu Q, Ma H*, Tian Y*, Lan F*. Ribosome 18S m6A Methyltransferase METTL5 Promotes Translation Initiation and Breast Cancer Cell Growth. Cell Rep. 2020 Dec 22;33(12):108544. doi: 10.1016/j.celrep.2020.108544. PMID: 33357433.

6. Wan J, Xing S, Ding L, Wang Y, Gu C, Wu Y, Rong B, Li C, Wang S, Chen K, He C, Zhu D, Yuan S, Qiu C, Zhao C, Nie L, Gao Z, Jiao J, Zhang X, Wang X, Ying T, Wang H, Xie Y*, Lu Y*, Xu J*, Lan F*. Human-IgG-Neutralizing Monoclonal Antibodies Block the SARS-CoV-2 Infection. Cell Rep. 2020 Jul 21;32(3):107918. doi: 10.1016/j.celrep.2020.107918. Epub 2020 Jul 3. PMID: 32668215; PMCID: PMC7332464.

7. Yao Chen, Ruitu Lv, Bowen Rong, Yuxuan Zheng, Zhen Lin, Ruofei Dai, Xi Zhang, Nannan Xie, Siqing Wang, Fuchou Tang*, Fei Lan* and Ming-Han Tong* (2020) Refined Spatial-temporal Epigenomic Profiling Reveals Intrinsic Connection between PRDM9-mediated H3K4me3 and the Fate of Double-stranded Breaks. Cell Research, 2020 Mar;30(3):256-268. doi: 10.1038/s41422-020-0281-1. Epub 2020 Feb 11.

8. Wenqi Xu, Jiahui Li, Bowen Rong, Bin Zhao, Mei Wang, Ruofei Dai, Qilong Chen, Hang Liu, Zhongkai Gu, Shuxian Liu, Rui Guo, Hongjie Shen*, Feizhen Wu*, Fei Lan* (2019) DNMT3A Reads and Connects Histone H3K36me2 to DNA methylation. Protein & Cell, 2019, Nov 22 Early online, PMID 31758527

9. Jianqing Wang*, Chenxi He, Peng Gao, Siqing Wang, Ruitu Lv, Huihui Zhou, Qidong Zhou, Ke Zhang, Jian Sun, Caibin Fan, Guanxiong Ding* and Fei Lan* (2019) HNF1B-mediated repression of SLUG is suppressed by EZH2 in aggressive prostate cancer. Oncogene, 2019, Oct 21 Early Online, PMID 31636385

10. Zhennan Shi, Siyuan Xu, Shenghui Xing, Ke Yao, Lei Zhang, Luxi Xue, Bisi Miao, Peng Zhou, Ming Wang, Guoquan Yan, Pengyuan Yang, Jing Liu, Zeping Hu*, Fei Lan*（2019）Mettl17, a Regulator of Mitochondrial Ribosomal RNA Modifications, Is Required for the Translation of Mitochondrial Coding Genes. FASEB J., 2019, Nov., 33(11), 13040-13050

11. Zhao B, Xu W, Rong B, Chen G, Ye X, Dai R, Li W, Chen J, Cai J, Song L, Luo ZQ, Zeng R, Shi Y, Han JJ, Lan F*. H3K14me3 Genomic Distributions and its regulation by KDM4 family demethylases. Cell Res. 2018 Nov;28(11):1118-1120. Epub 2018 Oct 18. (* Correspondence)

12. Wu D, Hu D, Chen H, Shi G, Fetahu IS, Wu F, Rabidou K, Fang R, Tan L, Xu S, Liu H, Argueta C, Zhang L, Mao F, Yan G, Chen J, Dong Z, Lv R, Xu Y, Wang M, Ye Y, Zhang S, Duquette D, Geng S, Yin C, Lian CG, Murphy GF, Adler GK, Garg R, Lynch L, Yang P, Li Y, Lan F, Fan J, Shi Y, Shi YG. Glucose-regulated phosphorylation of TET2 by AMPK reveals a pathway linking diabetes to cancer. Nature. 2018 Jul;559(7715):637-641. doi: 10.1038/s41586-018-0350-5. Epub 2018 Jul 18.

13. Zuo X, Rong B, Li L, Lv R, Lan F*, Tong MH*. The histone methyltransferase Setd2 is required for expression of acrosin-binding protein 1 and protamines and essential for spermiogenesis in mice. J. Boil. Chem. 2018 Jun 15;293(24):9188-9197. Epub 2018 May 1.  (* Correspondence)

14. Ma C, Karwacki-Neisius V, Tang H, Li W, Shi Z, Hu H, Xu W, Wang Z, Kong L, Lv R, Fan Z, Zhou W, Yang P, Wu F, Diao J, Tan L, Shi YG, Lan F*, Shi Y*. Nono, a Bivalent Domain Factor, Regulates Erk Signaling and Mouse Embryonic Stem Cell Pluripotency. Cell Rep. 2016 Oct 18;17(4):997-1007. (* Correspondence)

15. Shen H, Xu W, Guo R, Rong B, Gu L, Wang Z, He C, Zheng L, Hu X, Shao Z-M, Yang PY, Wu FZ, Shi YG, Shi Y* and Lan F*. Suppression of Enhancer Over-activation by a RACK7-Histone Demethylase Complex. Cell 2016 Apr 7;165(2):331-42. (* Correspondence)

16. Guo, R., Zheng, LJ., Park, J.W., Xu, WQ., Chen, H., Qiu, JS., Lv RT., Wang, ZT., Yang, PY., Wu, FZ., Shi, XB., Fu, XD., Shi, G.YJ., Xing, Y*., Lan, F*., and Shi, Y*. BS69/ZMYND11 Reads and Connects Histone H3.3 Lysine 36 Trimethylation-Decorated Chromatin to Regulated Pre-mRNA Processing. Mol Cell. 2014 Oct 23;56(2):298-310. (* Correspondence)

17. Qi HH, Sarkissian M, Hu GQ, Wang Z, Bhattacharjee A, Gordon DB, Gonzales M, Lan F, Ongusaha PP, Huarte M, Yaghi NK, Lim H, Garcia BA, Brizuela L, Zhao K, Roberts TM, Shi Y. Histone H4K20/H3K9 demethylase PHF8 regulates zebrafish brain and craniofacial development. Nature. 2010 Jul 22;466(7305):503-7.

18. Tsai MC, Manor O, Wan Y, Mosammaparast N, Wang JK, Lan F, Shi Y, Segal E, Chang HY.Long noncoding RNA as modular scaffold of histone modification complexes. Science. 2010 Aug 6;329(5992):689-93.

19. Lan F, Bayliss PE, Rinn JL, Whetstine JR, Wang JK, Chen S, Iwase S, Alpatov R, Issaeva I, Canaani E, Roberts TM, Chang HY, Shi Y.  A histone H3 lysine 27 demethylase regulates animal posterior development. Nature Article. 2007 Oct 11;449(7163):689-94. Epub 2007 Sep 12.

20. Lan F*, Collins RE*, De Cegli R, Alpatov R, Horton JR, Shi X, Gozani O, Cheng X, Shi Y. Recognition of unmethylated histone H3 lysine 4 links BHC80 to LSD1-mediated gene repression. Nature. 2007 Aug 9;448(7154):718-22. (* Co-first)

21. Lan F, Zaratiegui M, Villén J, Vaughn MW, Verdel A, Huarte M, Shi Y, Gygi SP, Moazed D, Martienssen RA, Shi Y. S. pombe LSD1 homologs regulate heterochromatin propagation and euchromatic gene transcription. Mol Cell. 2007 Apr 13;26(1):89-101.

22. Iwase S*, Lan F*, Bayliss P, de la Torre-Ubieta L, Huarte M, Qi HH, Whetstine JR, Bonni A, Roberts TM, Shi Y. The X-linked mental retardation gene SMCX/JARID1C defines a family of histone H3 lysine 4 demethylases. Cell. 2007 Mar 23;128(6):1077-88. Epub 2007 Feb 22. (* Co-first)

23. Shi X, Hong T, Walter KL, Ewalt M, Michishita E, Hung T, Carney D, Peña P, Lan F, Kaadige MR, Lacoste N, Cayrou C, Davrazou F, Saha A, Cairns BR, Ayer DE, Kutateladze TG, Shi Y, Côté J, Chua KF, Gozani O. ING2 PHD domain links histone H3 lysine 4 methylation to active gene repression. Nature. 2006 Jul 6;442(7098):96-9. Epub 2006 May 21.

24. Whetstine JR, Nottke A, Lan F, Huarte M, Smolikov S, Chen Z, Spooner E, Li E, Zhang G, Colaiacovo M, Shi Y. Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases. Cell. 2006 May 5;125(3):467-81. Epub 2006 Apr 6.

25. Shi Y, Lan F, Matson C, Mulligan P, Whetstine JR, Cole PA, Casero RA, Shi Y. Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell. 2004 Dec 29;119(7):941-53.

26. Shi Y, Sawada J, Sui G, Affar el B, Whetstine JR, Lan F, Ogawa H, Luke MP, Nakatani Y, Shi Y. Coordinated histone modifications mediated by a CtBP co-repressor complex. Nature. 2003 Apr 17;422(6933):735-8.