1991-1996  Beijing Medical University (Peking University Health Center), M.D.

1996-2002 Kurume University, Japan, Ph.D.

2002-2006 Research Associate, Mayo Clinic

2006-2011  Assistant Processor, University of Michigan Medical School

2011-2015  Associate Processor, University of Michigan Medical School

2015        Professor, University of Michigan Medical School

2015-2020 Professor, Beckman Research Institute, City of Hope

2020-      Professor, Westlake University .

The research interests of our laboratory include the mechanisms of DNA damage response, chromatin remodeling, epigenetic modifications, and their roles in tumorigenesis. As a principle investigator, I have extensive expertise and motivation necessary to successfully carry out the research projects that are supported by various funding agencies. The research conducted in my laboratory results a number of manuscripts published in leading journals. Eight trainees from my laboratory have successfully become independent investigators, established their own laboratories, and generated scientific contributions in the cancer research field. Our current research mainly focuses on the role of protein poly(ADP-ribosyl)ation in DNA damage repair and cancer chemotherapy. Poly(ADP-ribosyl)ation is an unique posttranslational modification induced by DNA damage. Targeting poly(ADP-ribosyl)ation by PARP inhibitors suppresses DNA damage repair and selectively kill tumor cells with DNA damage repair defectives. Our recent studies not only reveal the basic molecular pathway of poly(ADP-ribosyl)ation in DNA damage repair, but also suggest novel therapeutic targets in this pathway for future cancer treatment. In addition, we recently developed small molecule inhibitors specifically targeting dePARylation enzymes for cancer chemotherapy.

1. Kim H, Chen J* and Yu X*. (2007) Ubiquitin-binding protein RAP80 mediates BRCA1-dependent DNA damage responses. Science. 316: 1202-1205. (* co-corresponding authors)

2. Liu Z, Wu J, and Yu X. (2007) CCDC98 targets BRCA1 to DNA damage sites. Nature Structural and Molecular Biology. 14: 716-720.

3. Huen M, Grant R, Manke I, Minn K, Yu X*, Yaffe M* and Chen J*. (2007) The E3 ubiquitin ligase RNF8 propagates the DNA damage signal via an ubiquitin-dependent signaling pathway. Cell. 131: 901-914. (* co-corresponding authors)

4. Zhang F, Ma J, Wu J, Ye L, Cai H, Xia B * and Yu X*. (2009) PALB2 links BRCA1 and BRCA2 in the DNA damage response. Current Biology. 19: 524-529. (* co-corresponding authors)

5. Lu LY, Wu J, Ye L, Gavrilina GB, Saunders TL and Yu X. (2010) RNF8-dependent histone modifications regulate nucleosome removal during spermatogenesis. Developmental Cell. 18: 371-384.

6. Zhang F and Yu X. (2011) WAC, a partner of RNF20/40 complex, regulates histone H2B ubiquitination and gene transcription. Molecular Cell. 41: 384-397.

7. Wu J, Chen Y, Lu LY, Wu Y, Paulsen MT, Ljungman M, Ferguson DO and Yu X. (2011) Chfr and RNF8 synergistically regulate ATM activation. Nature Structural and Molecular Biology. 18: 761-768.

8. Chen Q, Chen Y, Bian C, Fujiki R and Yu X. (2013) TET2 promotes histone O-GlcNacylation during gene transcription. Nature. 493 :561-564.

9. Ma T, Chen Y, Zhang F, Yang C-Y, Wang S and Yu X. (2013) RNF111-dependent neddylation activates DNA damage-induced ubiquitination. Molecular Cell. 49: 897-907.

10. Li M and Yu X. (2013) Function of BRCA1 in the DNA damage response is mediated by ADPribosylation. Cancer Cell. 23: 693-704.

11. Lu L, Korakavi G, Kuang H and Yu X. (2013) Distinct DNA damage responses on male meiotic sex Chromosomes. Nature Communications. (3015)

12. Li M, Lu L, Yang C, Wang S and Yu, X. (2013) The FHA and BRCT domains recognize ADPribosylation during DNA damage response. Genes & Development. 27: 1752-1768.

13. Liu C, Wu J, Paudyal SC, You Z and Yu X. (2013) CHFR is important for the first wave of ubiquitination at DNA damage sites. Nucleic Acids Research. 41 (3): 1698-1710.

14. Chen Y, Chen Q, McEachin RC, Cavalcoli JD and Yu X. (2014) H2A.B facilitates transcription elongation at methylated CpG loci. Genome Research. 24: 570-579.

15. Zhang F, Chen Y, Li M and Yu X. (2014) The OB-fold motif is a poly(ADP-ribose)-binding domain that mediates DNA damage response. Proceedings of the National Academy of Sciences. 111: 7278-7283.

16. Bian C and Yu X. (2014) PGC7 suppresses TET3 for protecting DNA methylation. Nucleic Acids Research. 42 (5): 2893-2905.

17. Zhang F, Shi J, Chen S-H, Bian C and Yu X. (2015) The PIN domain of EXO1 recognizes poly(ADP-ribose) in DNA damage response. Nucleic Acids Research. 43 (22): 10782-10794.

18. Chen Q and Yu X. (2016) OGT restrains the expansion of DNA damage signaling. Nucleic Acids Research. 44 (19): 9266-9278.

19. Li M, Chen Q, Ma T, and Yu X. (2017) Targeting reactive nitrogen species suppresses hereditary pancreatic cancer Proceedings of the National Academy of Sciences 114: 7106-7111

20. Liu C, Vyas A, Kassab MA, Singh AK and Yu X. (2017) The role of poly ADP-ribosylation in the first wave of DNA damage response. Nucleic Acids Research. 45 (14): 8129-8141.

21. Wang J, Yuan Z, Cui Y, Xie R, Wang M, Ma Y, Yu X* and Liu X*. (2018) Structure basis for the inhibition of the methyl-lysine binding function of 53BP1 by NUDT16L1/TIRR. Nature Communications. 9: 2689. (* co-corresponding authors)

22. Chen Q, Kassab MA, Dantzer F and Yu X. (2018) PARP2 mediates branched poly-ADP-ribosylation in response to DNA damage. Nature Communications. 9: 3233.

23. Yang G, Liu C, Chen S-H, Kassab MA, Hoff JD, Walter NG and Yu X. (2018) Super-resolution imaging identifies PARP1 and the Ku complex acting as DNA double-strand break sensors. Nucleic Acids Research. 46 (7): 3446-3457.

24. Bian C, Zhang C, Vyas A, Chen S-H, Liu C, Luo T and Yu X. (2019) NADP+ is an endogenous PARP inhibitor in DNA damage response and tumor suppression. Nature Communications. 10: 693.

25. Chen S-H and Yu X. (2019) Targeting dePARylation selectively suppresses DNA repair-defective and PARP inhibitor-resistant malignancies. Science Advances. 5: eaav4340.

26. Chen S-H and Yu X. (2019) Human DNA ligase IV is able to use NAD+ as an alternative adenylation donor for DNA ends ligation. Nucleic Acids Research. 47 (3): 1321-1334.

27. Singh AK, Zhao B, Wang X, Li H, Qin H, Wu X, Ma Y, Horne D and Yu X. (2020) Selective targeting of TET catalytic domain promotes somatic cell reprogramming. Proceedings of the National Academy of Sciences. 117: 3621-3626.

28. Singh AK and Yu X. (2020) Tissue-specific-carcinogens as soil to seed BRCA1/2-mutant hereditary cancers. Trends in Cancer. 6: 559-568.

29. Yang G, Chen Y, Wu J, Chen S-H, Liu X, Singh AK and Yu X. (2020) Poly(ADP-ribosyl)ation mediates early phase histone eviction at DNA lesions. Nucleic Acids Research. 48 (6): 3001-3013.

30. Chen Q*, Bian C, Wang X, Liu X, Kassab MA, Yu Y and Yu X*. (2021) ADP-ribosylation of histone variant H2AX promotes base excision repair. The EMBO Journal. 40: e104542. (* co-corresponding authors)

31. Chen Q*, Ma K, Liu X, Chen S-H, Li P, Yu Y, Leung A and Yu X*. (2022) Truncated PARP1 mediates ADP-ribosylation of RNA polymerase III for apoptosis. Cell Discovery. 8: 3. (* co-corresponding authors)

32. Ma K, Luo M, Xie G, Wang X, Li Q, Gao L, Yu H and Yu X. (2022) Ribosomal RNA regulates chromosome clustering during mitosis. Cell Discovery. 8: 51.

33. Gai X, Xin D, Wu D, Wang X, Chen L, Wang Y, Ma K, Li Q, Li P and Yu X. (2022) Pre-ribosomal RNA reorganizes DNA damage repair factors in nucleus during meiotic prophase and DNA damage response. Cell Research. 32: 254-268.

yuxiaochun@westlake.edu.cn