|
RESEARCH FOCUS AREAS:
- Genomic stability in carcinogenesis and cancer therapy
- Colon cancer genetic risk factors
- Chemo-resistance in triple-negative breast cancer
- UV DNA damage repair
- Sensitizing cancer cells to chemo drugs
RESEARCH SUMMARY;
Genome instability is a hallmark of cancer. Faithful DNA replication is important for preventing detrimental replication errors and maintaining genome integrity. DNA replication frequently encounters obstacles arising from both cellular metabolic processes and environmental sources that slow or stall replication forks, which disrupts proper progression of replication and threatens genome stability. To protect genome integrity, cells have evolved a panoply of mechanisms to suppress replication fork stalling and rescue stalled replication. Understanding these mechanisms is important for understanding early events in carcinogenesis. In addition, recent research has revealed that targeting replication in tumor cells may offer a promising cancer therapeutic approach, in particular for treating cancers harboring mutations in DNA repair genes. The Chai lab integrates next-generation sequencing, molecular biology, cellular imaging methods, as well as in vivo animal models to understand the molecular mechanisms for protecting genome stability under replication stress. Our research will facilitate the development of more targeted and effective cancer therapy.
Training Opportunities in the Chai Lab:
Students, fellows, or residents who join Dr. Chai’s lab can expect to receive a wide range of training in advanced molecular biology, genomics (next-gen sequencing), cell biology, cell line construction (including CRISPR and viral transduction), advanced fluorescence microscopy, live cell imaging, chromosome stability, protein-protein interactions, cytogenetics, protein-DNA interactions, protein function, and working with mice to study carcinogenesis. They will also gain a broad knowledge of how genome instabilities caused by defective DNA repair pathways and/or telomere dysfunction drive tumor formation.
EDUCATION:
- BA in Microbiology, Shandong University, China
- PhD in Molecular Microbiology, Cornell University
- Postdoctoral fellowship in Cell Biology, University of Texas Southwestern Medical Center
SELECTED PUBLICATIONS:
- Deficiency in mammalian STN1 promotes colon cancer development via inhibiting DNA repair Nguyen DD, Kim E, Le NT, Ding X, Jaiswal RK, Kostlan RJ, Nguyen TNT, Shiva O, Le MT, Chai W. Sci Adv. 2023 May 10;9(19):eadd8023. doi: 10.1126/sciadv.add8023. Epub 2023 May 10. PubMed PMID: 37163605; PubMed Central PMCID: PMC10171824.
- Crosstalk between CST and RPA regulates RAD51 activity during replication stress Lei, KH; Yang, HL; Chang, HY; Yeh, HY; Nguyen, DD; Lee, TY; Lyu, X; Chastain, M; Chai, W; Li, HW; Chi, P Nature Communications 2021 Nov 5;12(1):6412. doi: 10.1038/s41467-021-26624-x. PMID: 34741010; PMCID: PMC8571288
- Human CST complex protects stalled replication forks by directly blocking MRE11 degradation of nascent-strand DNA Lyu, X; Lei, KH; Biak Sang, P; Shiva, O; Chastain, M; Chi, P; Chai, W EMBO J. 2021 Jan 15;40(2):e103654. doi: 10.15252/embj.2019103654. Epub 2020 Nov 19. PMID: 33210317; PMCID: PMC7809791
- Pathogenic CTC1 mutations cause global genome instabilities under replication stress Wang, Y; Chai, W Nucleic Acids Research 2018 May 4;46(8):3981-3992. doi: 10.1093/nar/gky114. PMID: 29481669; PMCID: PMC5934659
- Human CST facilitates genome-wide RAD51 recruitment to GC-rich repetitive sequences in response to replication stress Chastain, M; Zhou, Q; Shiva, O; Fadri-Moskwik, M; Whitmore, L; Jia, P; Dai, X; Huang, C; Ye, P; Chai, W Cell Reports 2016 Aug 2;16(5):1300-1314. PMID: 27533181; PMCID: PMC5669620
- Human MLH1 suppresses the insertion of telomeric sequences at intra-chromosomal sites in telomerase-expressing cells Jia, P; Chastain, M; Zou, Y; Her, C; Chai, W Nucleic Acids Research 2017 Feb 17;45(3):1219-1232. doi: 10.1093/nar/gkw1170. PMID: 28180301; PMCID: PMC5388398
- The FEN1 E359K germline mutation disrupts the FEN1-WRN interaction and FEN1 GEN activity, causing aneuploidy-associated cancers Chung, L; Onyango, D; Guo, Z; Jia, P; Dai, H; Liu, S; Zhou, M; Lin, W; Pang, I; Li, H; Yuan, YC; Huang, Q; Zheng, L; Lopes, J; Nicolas, A; Chai, W; Raz, D; Reckamp, KL; Shen, B Oncogene 2015 Feb 12;34(7):902-11. doi: 10.1038/onc.2014.19. Epub 2014 Mar 10. PMID: 24608430; PMCID: PMC4160428
- Mammalian DNA2 helicase/nuclease cleaves G-quadruplex DNA and is required for telomere integrity Lin, W; Sampathi, S; Dai, H; Liu, C; Zhou, M; Hu, J; Huang, Q; Campbell, J; Shin-Ya, K; Zheng, L; Chai, W; Shen, B EMBO Journal 2013 May 15;32(10):1425-39. doi: 10.1038/emboj.2013.88. Epub 2013 Apr 19. PMID: 23604072; PMCID: PMC3655473
- Human Stn1 protects telomere integrity by promoting efficient lagging-strand synthesis at telomeres and mediating C-strand fill-in Huang, C; Dai, X; Chai, W Cell Research 2012 Dec;22(12):1681-95. doi: 10.1038/cr.2012.132. Epub 2012 Sep 11. PMID: 22964711; PMCID: PMC3515754
- Molecular steps of G-overhang generation at human telomeres and its function in chromosome end protection Dai, X; Huang, C; Bhusari, A; Sampathi, S; Schubert, K; Chai, W EMBO Journal 2010 Aug 18;29(16):2788-801. doi: 10.1038/emboj.2010.156. Epub 2010 Jul 16. PMID: 20639858; PMCID: PMC2924643
FULL LIST OF PUBLICATIONS
|
