WEIHANG CHAI, PhD
- PhD, Cornell University
- Bachelor of Science, Shandong University
- UT Southwestern Medical Center at Dallas, postdoctoral research in Cell Biology
- NIH NRSA postdoctoral fellowship
Dr. Weihang Chai has mentored graduate students and trained postdoctoral fellows at WSU. She currently has two postdoctoral trainees in her research lab, and is on dissertation committees for graduate students from the School of Molecular Biosciences and College of Pharmacy. In addition, she was the course chair for the immunology curriculum for first-year medical students at WSU Spokane from 2009-2014.
The overall goal of research in my lab is to understand the mechanisms governing genome stability, and more importantly, how we can apply new knowledge to prevent genome instability as well as to fight against cancer and aging-related diseases. We are carrying out three areas of research in parallel: a) maintenance of the stability of fragile sites in the genome in response to environmental genotoxins, b) maintenance of telomere integrity, and c) translational research. We apply innovative approaches including next-generation sequencing, advanced fluorescent microscopy, and genome editing to accomplish our research goals.
Research Area 1 – Understanding the maintenance of genome stability in response to replication stress induced by environmental genotoxins (funded by R01): DNA damage constitutes a major threat to genetic integrity, and has thus been implicated in the pathogenesis beyond cancer. Elucidating the mechanism safeguarding genome stability is important for understanding the mechanism underlying carcinogenesis. Genome integrity is constantly threatened by endogenous and exogenous agents arising from cellular metabolic processes as well as environmental exposure, many of which impede normal DNA replication and cause replication fork stalling. Stalled forks need to be properly repaired and rescued to prevent DNA lesions and genome instabilities that contribute to tumorigenesis. To repair and rescue stalled replication, a network of proteins regulating DNA damage response, DNA repair, replication, and cell cycle checkpoints are activated in response to stalled replication in order to stabilize and restart stalled forks. However, the mechanism underlying fork repair is poorly understood. We and others have found that the CTC1/STN1/TEN1 complex (CST) is a novel guardian that protects genome stability in human cells. Our lab is focusing on understanding the functions of this novel player in protecting genome stability under replication stress, in particular, what is the role of CST in restarting stalled replication; what molecular mechanism CST employs to counter replication stress; as well as how it interplays with other proteins to accurately restart stalled forks. In addition, we are interested in applying knowledge learned from our basic research to facilitate the design of cancer therapy by targeting replication stress.
Research Area 2 – Mechanism for telomere maintenance: Telomeres, the physical ends of eukaryotic chromosomes, play a key role in protecting genome stability. Telomere is a unique structure consisting of tandem repetitive DNA sequence, telomere binding proteins, and unique telomeric heterochromatin. These telomeric components are precisely assembled at chromosome ends, and they interact with each other in an orderly manner to ensure that telomere integrity is preserved. Disruption of telomere integrity causes chromosomal abnormalities, leading to cancer and premature aging disorders. Therefore, revealing the roles of telomeric components in maintaining telomere integrity is expected to assist in devising effective anti-aging and anti-cancer strategies. We are interested in understanding how telomere stability is maintained in human cells.
Research Area 3 – Understanding the role of telomere sequence insertion in carcinogenesis (funded by R03). Telomeric repeats are usually confined at chromosome ends. Aberrant insertion of telomeric sequences into intra-chromosomal regions (known as telomere sequence insertion, or TSI) leads to genome instabilities that contribute to carcinogenesis, and thus must be suppressed. The mechanism underlying such suppression is currently unknown. Recently, we unexpectedly discovered that TSI may arise from erroneous telomeric sequence addition by telomerase at or near DSBs. This is consistent with previous reports that telomerase is able to promiscuously add telomeric repeats to non-telomeric templates. We also identify that MLH1 plays an important role in suppressing TSI. We are interested in understanding how TSI is suppressed in human cells and how dysregulation of TSI suppression contributes to cancer formation.
- Associate Professor (tenured), Elson S. Floyd College of Medicine
- Board member, the inaugural Cancer Research Endowment Authority Board, the State of Washington Governor’s Office
- Editorial board member for the journal “Frontiers in Cancer Molecular Targets and Therapeutics”
- Editorial board member for “Journal of Molecular and Genetic Medicine”
- Scientific Director, Microscopy Imaging Core Facility at WSU-Spokane
- Member, Institute of Translational Health Sciences, the State of Washington
- Member, Center for Reproductive Biology, Washington State University
- Associate Faculty, School of Molecular Biosciences, WSU Pullman
- Affiliate Faculty, Dept of Pharmaceutical Sciences, College of Pharmacy, Washington State University
- 2005 Scholarship Award from Keystone Symposium in Genome Instability and Repair
- 2004 The Scholar-in-Training Award from American Association for Cancer Research
- The American Aging Association Paul Glenn Award for meritorious research in biomedical gerontology
- 2003-4 NIH Ruth L. Kirschstein National Research Service Award Individual Fellowship
Principle Investigator: Weihang Chai, PhD, Associate Professor
- Eugene Kim, PhD, Senior Research Scientist
- Xinxing Lyu, PhD, Postdoc Researcher
- Megan Chastain, MS, Research Assistant
- Olga Shiva, BS, Research Assistant
- Shilpa Sampathi, PhD: 2006-2011
Current position: Postdoc at Vanderbelt University School of Medicine
- Amruta Bhusari, M.S.: 2006-2008
Current position: Research Assistant at Dept of Nephrology and Hypertension, Oregon Health and Science University
- Xueyu Dai, PhD: 2009-2012
- Chenhui Huang, PhD: 2009-2013
- Maria Fadri-Moskwik, PhD: 2012-2014
- Qing (Vivian) Zhou, PhD: 2013-2015
- Pingping Jia, PhD: 2012-2016
- Faya Zhang, PhD: 2017 July-Dec.
- Yuan Wang, PhD: 2016-2018
- Emiliano Reed: Undergrad from WSU.
- Jacob Mallery: Undergrad from WSU.
- Bryce Burnett: Undergrad from EWU.
- Annie Morgan: Undergraduate from Harvard Univ. Currently enrolled in MD, PhD program at Harvard.
- Kathryn Schubert: Undergraduate from Gonzaga Univ.
- Cora Hartill: Undergraduate from EWU
- Natalie Schennum: Undergraduate from Gonzaga Univ.
- Alex Diamond: Undergrad from Gonzaga Univ.
Selected Publications (since joining WSU)
- Wang, Y., *Chai, W. (2018) Pathogenic CTC1 mutations cause global genome instabilities under replication stress. Nucleic Acids Res. 46 (8): 3981-3992.
- Jia P., *Chai W. (2018) The MLH1 ATPase domain is needed for suppressing aberrant formation of interstitial telomeric sequences. DNA repair. 65:20-25.
- 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.
- 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.
- 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
- 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
- Jia, P., Her, C., *Chai, W. (2015) DNA Excision Repair at Telomeres. DNA Repair. 36:137-45.
- 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
- 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
- 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.
- 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)
- *Chai, W., Zheng, L., Shen, B. (2013) DNA2, a new player in telomere maintenance and tumor suppression. Cell Cycle. Accepted. (Impact factor: 5.359)
- 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)
- 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)
- 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)
- 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)
- 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)
- Sampathi, S. and *Chai, W. (2011) Telomere replication: poised but puzzling. J. Cellular and Molecular Medicine. 15(1): 3-13. (Impact factor: 4.608)
- 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)
- 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)