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Profiles

Weihang "Valerie" Chai, PhD

Professor

Cancer Biology

Research Interests:

  • 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

Contact
  • CBCC 236
  • https://weihangchai.wixsite.com/chailab/about
    • Education
    • BA in Microbiology, Shandong University, China
    • PhD in Molecular Microbiology, Cornell University
    • Postdoctoral fellowship in Cell Biology, University of Texas Southwestern Medical Center

    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.

    Research Interests

    • 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

    Publications

    • 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

    Additional Publications List