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Weihang (Valerie) Chai, PhD

Weihang (Valerie) Chai, PhD
Professor
weihang.chai@rosalindfranklin.edu
Microbiology and Immunology
Chicago Medical School, School of Graduate and Postdoctoral Studies

Dr. Chai earned her PhD in Microbiology from Cornell University before undertaking postdoctoral fellowship training in the laboratories of Drs. Jerry Shay and Woodring Wright at UT Southwestern Medical Center in Dallas. There, she delved into the roles of telomere structure and replication in cancer and aging. In 2008, she founded her own laboratory at Washington State University, focusing on genome stability mechanisms. After advancing through the ranks and securing tenure, she relocated to Chicago just before the COVID-19 pandemic, joining the Department of Cancer Biology at Loyola University Chicago Stritch School of Medicine as a tenured Full Professor. Recently, she was appointed Director of the Center for Genetic Diseases at the Chicago Medical School, Rosalind Franklin University of Medicine and Science.

Dr. Chai's research aims to uncover how genome stability is maintained amid disrupted DNA replication and to explore how mutations linked to diseases destabilize the genome, contributing to cancer and complex diseases. Her team was the first to show that the CST protein complex binds to ssDNA at stalled replication forks, thereby preserving their stability. Currently, her lab investigates how cancer cells shield their genome from being damaged by chemotherapeutic drugs, a mechanism contributing to chemo-resistance. Dr. Chai’s research has been continuously funded by NIH R01 grants. She has contributed to multiple NIH and DOD study sections, is a standing member of the NIH Molecular Genetics study section, and serves on the editorial boards of various scientific journals.

Publications

  1. Sang P.B, Jaiswal, R.K., Lyu, X., *Chai, W. (2024) Human CST complex restricts excessive PrimPol repriming upon UV induced replication stress by suppressing p21. Nucleic Acids Research, gkae078 (IF: 14.9)
  2. Jaiswal, R.K., Lei, K-H., Chastain, M., Wang, Y., Shiva, O., Li, S., You, Z., Chi, P., *Chai, W. (2023) CaMKK2 and CHK1 phosphorylate human STN1 in response to replication stress to protect stalled forks from aberrant resection. Nature Comm. 14, Article number: 7882. PMID: 38036565
  3. Nguyen, D.D., Kim, E., Le, N.T., Ding, X., Jaiswal, R.K., Kostlan, R.J., Nguyen, T.N.T., Shiva, O., Le, M.T., Chai, W. (2023) Deficiency of mammalian STN1 promotes colon cancer development via inhibiting DNA repair. Science Advances 9 (19): eadd8023. PMID: 37163605 (IF: 14.98)
  4. Lei, K-H., Yang, H-L., Nguyen, D-D, Chang, H-Y, Yeh, H-Y., Lee, T-Y., Lyu, X., Chai, W., Li, W-L., Chi, P. (2021) Crosstalk between CST and RPA regulates RAD51 activity during replication stress. Nature Comm. 12(1):6412. PMID: 34741010. (IF: 14.919)
  5. Chai, W., Chastain, M., Shiva, O., Wang, Y. (2021) The intrinsic disordered region in the human STN1 OB-fold domain is important for protecting genome stability. Biology. 10, 977. https://doi.org/10.3390/biology10100977
  6. Lyu, X., Sang, P. S., *Chai, W. (2021) CST in maintaining genome stability: beyond telomeres. DNA Repair. 102: 103104. (Review)
  7. Lyu, X., Lei, K-H., Sang, P. S., Shiva, O., Chastain, M., Chi, P., *Chai, W. (2021) Human CST complex protects replication fork stability by directly blocking MRE11 degradation of nascent strand DNA. EMBO J. doi: 10.15252/embj.2019103654
  8. Nguyen D-D., Kim, E. Y., Sang, P. B., *Chai, W. (2020) Roles of OB-Fold Proteins in Replication Stress. Frontiers in Cell and Developmental Biology. Vol 8 | Article 574466. PMID: 33043007 (Review)
  9. Lyu, X., Chastain, M., Chai, W.* (2019) Genome-wide mapping and profiling of gH2AX binding hotspots in response to different replication stress inducers. BMC Genomics. 20 (1): 579-592.
  10. Wang, Y., Chai, W.* (2018) Pathogenic CTC1 mutations cause global genome instabilities under replication stress. Nucleic Acids Res. 46 (8): 3981-3992. (IF: 10.162)
  11. Jia P., Chai, W. * (2018) The MLH1 ATPase domain is needed for suppressing aberrant formation of interstitial telomeric sequences. DNA Repair. 65:20-25. (IF: 3.61)
  12. Huang, C., Jia, P., Chastain, M., Shiva, O., Dai, X., *Chai, W. (2017) The Human CTC1/STN1/TEN1 Complex Localizes in ALT-Associated PML Bodies and Regulates Telomere maintenance in ALT cancer cells. Exp Cell Res. 355(2):95-104.
  13. Jia, P., Chastain, M., Zou, Y., Her, C., *Chai, W. (2017) Human MLH1 suppresses the insertion of telomeric sequences at intra-chromosomal sites in telomerase-expressing cells. Nucleic Acids Res. 45(3):1219-1232. doi: 10.1093/nar/gkw1170.
  14. Chastain, M., Zhou, Q., Shiva, O., Fadri-Moskwik, M., Whitmore, L., Jia, P., Dai, X., Huang, C., Ye, P., *Chai, W. (2016) Human CST facilitates genome-wide RAD51 recruitment to GC-rich repetitive sequences in response to replication stress. Cell Reports. 16(5):1300-14
  15. Zhou, Q.V., Sampathi, S., *Chai, W. (2016) Suppression of STN1 Enhances the Cytotoxicity of Chemotherapeutic Agents in Cancer Cell Lines by Increasing DNA Damages. Oncology Letters. 12(2):800-808
  16. Jia, P., Her, C., *Chai, W. (2015) DNA Excision Repair at Telomeres. DNA Repair. 36:137-45.
  17. Chung, L., Onyango, D., Guo, Z., Jia, P., Dai, H., Lin, W., Pang, I., Li, H., Yuan, Y., Huang, Q., Zheng, L., Lopes, J., Nicolas, A., Chai, W., Raz, D., Reckamp, K.L., Shen, B. (2015) The FEN1 E359K mutation isolated from a breast cancer patient disrupts the FEN1-WRN interaction and FEN1 GEN activity, causing aneuploidy-associated cancers. Oncogene. 34(7):902-11. PMID: 24608430
  18. Shi, J., Yang, X.R., Ballew, B., Rotunno, M., Calista, D., Fargnoli, M.C., Ghiorzo, P, Bressac-de Paillerets, B., Nagore, E., Avril, M.F., Caporaso, N.E., McMaster, M.L., Cullen, M., NCI DCEG Cancer Sequencing Working Group, NCI DCEG Cancer Genomics Research Laboratory, French Familial Melanoma Study Group, Bruno, W., Pastorino, P., Queirolo, P., Banuls-Roca, J., Garcia-Casado, Z., Vaysse, A., Mohamdi, H., Riazalhosseini, Y., Foglio, M., Jouenne, F., Hua, X., Hyland, P.L., Yin, J., Vallabhaneni, H., Chai, W., Minghetti, P., Pellegrini, C., Ravichandran, S., Eggermont, S., Lathrop, M., Peris, K., Scarra, G.B., Landi, G., Savage, S.A., Sampson, J.N., He, J., Yeager, M., Goldin, L.R., Demenais, F., Chanock, S.J., Tucker, M.A., Goldstein, A.M., Liu, Y., Landi, M.T. (2014) Rare missense variants in POT1 predispose to familial cutaneous malignant melanoma. Nature Genetics. 46(5):482-6. PMID: 24686846
  19. Fadri-Moskwik, F., Zhou, V.Q., *Chai, W. (2013) Beyond Telomerase: Telomere Instability as a Novel Target for Cancer Therapy. J Mol Genet Med. 7: 91 DOI: 10.4172/1747-0862.10000 91.
  20. Lin, W., Sampathi, S., Dai, H., Liu, C., Zhou, M. Hu, J., Huang, Q., Campbell, J., Zheng, L., *Chai, W., Shen, B. (2013) Mammalian DNA2 cleaves G-quadruplex DNA and is required for telomere integrity. EMBO J. 32(10):1425-39 (Impact factor: 10.124) (co-corresponding author)
  21. *Chai, W., Zheng, L., Shen, B. (2013) DNA2, a new player in telomere maintenance and tumor suppression. Cell Cycle. Accepted. (Impact factor: 5.359)
  22. Huang, C., Dai, X., and *Chai, W. (2012) Human Stn1 protects telomere integrity by promoting efficient lagging-strand synthesis at telomeres and mediating C-strand fill-in. Cell Research. 22 (12) 1681-1695 (Impact factor: 8.190)
  23. Dai, X., Huang, C., and *Chai, W. (2012) CDK1 differentially regulates G-overhang generation at leading- and lagging-strand telomeres in telomerase negative cells in the G2 phase. Cell Cycle. 11 (16) 2959-3142. (Impact factor: 5.359)
  24. Gu, P., Min, J., Wang, Y., Huang, C., Chai, W. and Chang, S. (2012) CTC1 deletion results in defective telomere replication, leading to catastrophic telomere loss and stem cell exhaustion. EMBO J. 31(10):2309-21. (Impact factor: 9.205)
  25. Wu, X., Xu, Y., Chai, W. and Her, C. (2011) The causal link between microsatellite instability and hMRE11 dysfunction in human cancers. Molecular Cancer Res. 9(11):1443-8. (Impact factor: 4.16)
  26. Sampathi, S. and *Chai, W. (2011) Mapping the domain of FEN1/hTERT association. Biochem Biophys Res Comm. 407 (1): 34-38. (Impact factor: 2.855) (corresponding author)
  27. Sampathi, S. and *Chai, W. (2011) Telomere replication: poised but puzzling. J. Cellular and Molecular Medicine. 15(1): 3-13. (Impact factor: 4.608) (corresponding author)
  28. Dai, X., Huang, C., Bhusari, A., Sampathi, S, Schubert, K. and *Chai, W. (2010) Molecular steps of G-overhang generation at human telomeres and its function in chromosome end protection. EMBO J. 29(16):2788-801. (Impact factor: 10.124)
  29. Sampathi, S, Bhusari, A., Shen, B., *Chai, W. (2009) Human flap endonuclease I is in complex with telomerase and is required for telomerase-mediated telomere maintenance. J. Biol. Chem. 284(6):3682-90. (Impact factor: 5.328)

Prior to independence:

  1. Gardner, J.P., Kimura, M., Chai, W., Durrani, J.F., Tchakmakjian, L. Cao, X., Lu, X., Li, G., Peppas, Skurnick, T.J., Wright, W.E., Shay, J.W., Aviv, A. (2007) Telomere dynamics in macaques and humans. J. Gerontology: Biol. Sci. Med. Sci., 62(4): 367-374.
  2. Chai, W., Du, Q., Shay, J. W., Wright, W.E. (2006) Human telomeres have difference overhang sizes at the leading versus lagging strands. Mol. Cell 21(3): 427-435.
  3. Chai, W., Sfeir, A.J., Hoshiyama, H., Shay, J.W., Wright, W.E. (2006) The involvement of the Mre11/Rad50/Nbs1 complex in the generation of G-overhangs at human telomeres. EMBO Reports. 7(2):225-230.
  4. Sfeir, A.J., Chai, W., Shay, J.W., Wright, W.E. (2005) Telomere end processing: the last base of mammalian chromosomes. Mol. Cell 18 (1): 131-138.
  5. Chai, W., Shay, J. W., Wright, W.E. (2005) Human cells maintain their telomere overhangs at senescence. Mol. Cell Biol. 25 (6): 2158-2168.
  6. Sawyer, S., Cheng I.H., Chai, W., and Tye, B.K. (2004) Mcm10 and Cdc45 cooperate in origin activation in Saccharomyces cerevisiae. J. Mol. Biol. 340 (2): 195-202.
  7. Chai, W., Ford, L.P., Lenertz, L., Wright, W.E., Shay, J.W. (2002) Human Ku70/80 associates physically with telomerase through interaction with hTERT. J. Biol. Chem. 277, 47242-47247.
  8. Chai, W. and Stewart, V. (1999) RNA sequence requirements for NasR-mediated, nitrateresponsive transcription antitermination in the Klebsiella oxytoca M5al nasF operon leader. J. Mol. Biol. 292 (2): 203-216
  9. Chai, W. and Stewart, V. (1998) NasR, a novel RNA-binding protein, mediates nitrate-responsive transcription antitermination of the Klebsiella oxytoca M5al nasF operon leader in vitro. J. Mol. Biol. 283 (3), 339-351
  10. Wu, Q, Chai, W., Lin, J. T. and Stewart, V. (1999) General nitrogen regulation (Ntr) of nitrate assimilation regulatory gene nasR expression in Klebsiella oxytoca M5al. J. Bacteriology 181 (23): 7274-7284