Xiaojiang Chen

• Postdoctoral Fellow, Harvard University, 1994-1999

Tenure Track Appointments

• Full Professor, University of Southern California, 2006 –
• Associate Professor, University of Southern California, 2004 – 2006
• Associate Professor, University of Colorado School of Medicine, 2003 – 2004
• Assistant Professor, University of Colorado School of Medicine, 1999 – 2003

Summary Statement of Research Interests

Dr. Xiaojiang Chen’s combined expertise in Molecular and Cell Biology, Biochemistry, and Structural Biology (X-ray, EM) enables him to study critical questions in DNA replication/repair, Cancer Biology and Immunology at molecular/cellular levels. He has done landmark work on viral replication and viral oncogenes (such as SV40 large tumor antigen, EBV gp350), as well as crucial DNA modifying enzymes which play key roles in genomic stability, cancer, and immunity. His current research interests are (1) APOBEC family of cytidine deaminases (DNA mutases) involved in cancer and immune responses to viruses (HIV, HPV, HBV); (2) DNA/RNA transaction enzymes, including helicases, polymerases/primase for DNA replication and repair which are involved in genomic stability, cell proliferation, and cancer; (3) viral oncoproteins and cellular tumor suppressors; (4) nano-particle assembly for targeted drug delivery.

Research Keywords

Cancer; Immunity; Oncogenes, Tumor suppressor, DNA modifying enzymes; nano-machine; Helicases; APOBEC deaminase; Structural Biology, Biochemistry, Molecular Biology, Cell Biology

Journal Article

• Fried, W., Tyagi, M., Minakhin, L., Chandramouly, G., Treddinnick, T., Rusanov, T., Hoang, T., Betsch, R., Krais, J., Wang, Y., Gordon, J., Morton, G., Kent, T., Skorski, T., Johnson, N., Childers, W., Chen, X. S., Pomerantz, R. T. (2024). Discovery of a Small-Molecule Inhibitor that Traps Pol-theta on DNA and Synergizes with PARP Inhibitors. Nature Comm.. Vol. 2024 Apr 5;15(1):2862 doi: 10.1038/s41467-024-46593-1
• Ito, F., Yang, H., Zhou, Z. H., Chen, X. S. (2024). Structural basis for polyuridine tract recognition by SARS-CoV-2 Nsp15. Protein Cell. Vol. 2024 Apr 13 doi: 10.1093/procel/pwae009
• Sanchez, A., Ortega, P., Sakhtemani, R., Manjunath, L., Oh, S., Bournique, E., Becker, A., Kim, K., Durfee, C., Temiz, N., Chen, X. S., Harris, R. S., Lawrence, M., Buisson, R. (2024). Mesoscale DNA Features Impact APOBEC3A and APOBEC3B Deaminase Activity and Shape Tumor Mutational Landscapes. Nature Comm.. Vol. 2024 Mar 18;15(1):2370. 10.1038/s41467-024-45909-5
• Ito, F., Alvarez, A., Liu, S., Zhou, H., Chen, X. S. (2023). Structural basis of HIV-1 Vif mediated E3 ligase targeting of host APOBEC3H. Nature Comm.. Vol. 2023, 14, pp. 5241. https://www.nature.com/articles/s41467-023-40955-x
• Ito, F., Alvarez, A., Liu, S., Yang, H., Shiriaeva, A., Zhou, H., Chen, X. S. (2023). Structural basis for HIV-1 antagonism of host APOBEC3G via Cullin E3 ligase. Science Adv.. Vol. 9 (1), pp. 1-12. https://www.science.org/doi/10.1126/sciadv.ade3168
• Yang, H., Kim, K., Liu, S., Pacheco, J., Chen, X. S. (2022). Structural basis of sequence-specific RNA recognition by the antiviral factor APOBEC3G. Nature Comm.. Vol. 13, pp. 7498. https://www.nature.com/articles/s41467-022-35201-9
• Yang, H., Kim, K., Li, S., Pacheco, J., Chen, X. S. (2022). Structural basis of sequence-specific RNA recognition by the antiviral factor APOBEC3G. Nature Comm.. Vol. 13, pp. 7498. https://www.nature.com/articles/s41467-022-35201-9
• Chandramouly, G., Zhao, J., McDevitt, S., Rusanov, T., Hoang, T., Borisonnik, N., Lopezcolorado, F. W., Kent, T., Mallon, J., Kashkina, E., Brambati, A., Stark, J. M., Chen, X. S., Pomerantz, R. T. (2021). Polθ reverse transcribes RNA and promotes RNA-templated DNA repair. Science Adv.. Vol. 7, pp. 7(24). https://www.science.org/doi/10.1126/sciadv.abf1771
• Wolfe, A. D., Li, S., Goedderz, C., Chen, X. S. (2020). The structure of APOBEC1 and insights into its RNA and DNA substrate selectivity. NAR Cancer. Vol. 2 (42020/10/24), pp. zcaa027.
• Yang, H., Ito, F., Wolfe, A. D., Li, S., Mohammadzadeh, N., Love, R. P., Yan, M., Zirkle, B., Gaba, A., Chelico, L., Chen, X. S. (2020). Understanding the structural basis of HIV-1 restriction by the full length double-domain APOBEC3G. Nature Commun. Vol. 11 (12020/02/02), pp. 632.
• Schlierf, M., Wang, G., Chen, X. S., Ha, T. (2019). Hexameric helicase G40P unwinds DNA in single base pair steps. Elife. Vol. 8 (2019/01/29)
• Ito, F., Yang, H., Xiao, X., Li, S. X., Wolfe, A., Zirkle, B., Arutiunian, V., Chen, X. S. (2018). Understanding the Structure, Multimerization, Subcellular Localization and mC Selectivity of a Genomic Mutator and Anti-HIV Factor APOBEC3H. Sci. Rep. Vol. 8 (12018/03/02), pp. 3763.
• Xiao, X., Yang, H., Arutiunian, V., Fang, Y., Besse, G., Morimoto, C., Zirkle, B., Chen, X. S. (2017). Structural determinants of APOBEC3B non-catalytic domain for molecular assembly and catalytic regulation. Nucleic Acids Res. Vol. 45 (122017/06/03), pp. 7494-7506.
• Xiao, X., Li, S. X., Yang, H., Chen, X. S. (2016). Crystal structures of APOBEC3G N-domain alone and its complex with DNA. Nature Commun. Vol. 7, pp. 12193.
• Quan, Y., Xia, Y., Liu, L., Cui, J., Li, Z., Cao, Q., Chen, X. S., Campbell, J. L., Lou, H. (2015). Cell-Cycle-Regulated Interaction between Mcm10 and Double Hexameric Mcm2-7 Is Required for Helicase Splitting and Activation during S Phase. Cell Rep. Vol. 13 (11), pp. 2576-86.
• Yu, J., Greenleaf, W. B., Shi, Y. S., Chen, X. S. (2014). Mechanism of Subunit Coordination of An AAA+ Hexameric Molecular Nanomachine. Nanomedicine. pp. Dec 30. pii: S1549-9634(14)00567.
• Chang, Y. P., Xu, M., Machado, A. C., Yu, X. J., Rohs, R., Chen, X. S. (2013). Mechanism of origin DNA recognition and assembly of an initiator-helicase complex by SV40 large tumor antigen. Cell reports. Vol. 3 (4), pp. 1117-27. PubMed Web Address
• Patrick, A. N., Cabrera, J. H., Smith, A. L., Chen, X. S., Ford, H. L., Zhao, R. (2013). Structure-function analyses of the human SIX1-EYA2 complex reveal insights into metastasis and BOR syndrome. Nature structural & molecular biology. Vol. 20 (4), pp. 447-53. PubMed Web Address
• Slaymaker, I. M., Fu, Y., Toso, D. B., Ranatunga, N., Brewster, A., Forsburg, S. L., Zhou, Z. H., Chen, X. S. (2013). Mini-chromosome maintenance complexes form a filament to remodel DNA structure and topology. Nucleic acids research. Vol. 41 (5), pp. 3446-56. PubMed Web Address
• Shi, Y., Liu, H., Gai, D., Ma, J., Chen, X. S. (2009). A computational analysis of ATP binding of SV40 large tumor antigen helicase motor. PLoS computational biology. Vol. 5 (9), pp. e1000514. PubMed Web Address
• Liu, H., Shi, Y., Chen, X. S., Warshel, A. (2009). Simulating the electrostatic guidance of the vectorial translocations in hexameric helicases and translocases. PNAS. Vol. 106 (18), pp. 7449-54. PubMed Web Address
• Prochnow, C., Goodman, M. F., Chen, X. S. (2009). The prospct of APOBEC3G for the future of HIV therapy. HIV Ther. Vol. 3(1) (2009/01), pp. 7-10.
• Brewster, A. S., Wang, G., Yu, X., Greenleaf, W. B., Carazo, J. M., Tjajadi, M., Klein, M. G., Chen, X. S. (2008). A near-full-length archaeal MCM structure: functional insights for an AAA+ hexameric helicase. Proceedings of the National Academy of Sciences of the United States of America. Vol. 105 (51), pp. 20191-6. PubMed Web Address
• Holden, L. G., Prochnow, C., Chang, Y. P., Bransteitter, R., Chelico, L., Sen, U., Stevens, R. C., Goodman, M. F., Chen, X. S. (2008). Structure of the anti-viral APOBEC3G catalytic domain and functional implications. Nature. Vol. 456 (7218), pp. 121-4. PubMed Web Address
• Wang, G., Klein, M. G., Tokonzaba, E., Zhang, Y., Holden, L. G., Chen, X. S. (2008). A DnaB-family replicative helicase structure and its interactions with primase. Nature struct mol biology. Vol. 15 (1), pp. 94-100. PubMed Web Address
• Chang, Y. P., Wang, G., Bermudez, V., Hurwitz, J., Chen, X. S. (2007). Crystal structure of the GINS complex and functional insights into its role in DNA replication. Proceedings of the National Academy of Sciences of the United States of America. Vol. 104 (31), pp. 12685-90. PubMed Web Address
• Prochnow, C., Bransteitter, R., Klein, M. G., Goodman, M. F., Chen, X. S. (2007). The APOBEC-2 crystal structure and functional implications for the deaminase AID. Nature. Vol. 445 (7126), pp. 447-51. PubMed Web Address
• Szakonyi, G., Klein, M. G., Hannan, J. P., Young, K. A., Ma, R. Z., Asokan, R., Holers, V. M., Chen, X. S. (2006). Structure of the Epstein-Barr virus major envelope glycoprotein. Nature structural & molecular biology. Vol. 13 (11), pp. 996-1001. PubMed Web Address
• Lilyestrom, W., Klein, M. G., Zhang, R., Joachimiak, A., Chen, X. S. (2006). Crystal structure of SV40 large T-antigen bound to p53: interplay between a viral oncoprotein and a cellular tumor suppressor. Genes & development. Vol. 20 (17), pp. 2373-82. PubMed Web Address
• Gai, D., Zhao, R., Li, D., Finkielstein, C. V., Chen, X. S. (2004). Mechanisms of conformational change for a replicative hexameric helicase of SV40 large tumor antigen. CELL. Vol. 119 (1), pp. 47-60. PubMed Web Address
• Fletcher, R. J., Bishop, B. E., Leon, R. P., Sclafani, R. A., Ogata, C. M., Chen, X. S. (2003). The structure and function of MCM from archaeal M. Thermoautotrophicum. Nature Struct Biol.. Vol. 10 (3), pp. 160-7..
• Li, D., Zhao, R., Lilyestrom, W., Gai, D., Zhang, R., DeCaprio, J. A., Fanning, E., Jochimiak, A., Szakonyi, G., Chen, X. S. (2003). Structure of the replicative helicase of the oncoprotein SV40 large tumour antigen. Nature. Vol. 423 (69392003/05/30), pp. 512-8.
• Boackle, S., Holers, M. V., Chen, X., Szakonyi, G., Karp, D., Wakeland, E. K., L., M. L. (2001). Cr2, a candidate gene in the murine Sle1c lpus susceptibility locus, encodes a dysfunctional protein. Immunity. Vol. 15., pp. 775-785.
• Szakonyi, G., Guthridge, J., Li, D., Young, K., Holers, M., Chen, X. (2001). Structure of complement receptor 2 in complex with its C3d ligand. Science. Vol. 292 (5522), pp. 1725-8..

• American Association for the Advancement of Science Fellow, Elected Fellow (AAAS), 2017
• Innovative Developmental Exploratory Awards, 2009
• American Cancer Society Foundation Young Investigator’s Award, 2003
• Basil O’Connor Scholar Research Award, 2002
• Howard Hughes Medical Institute Junior Faculty Start-Up Award, 2000
• University of California Tom-Shell Award for Outstanding Dissertation, 1992

Administrative Appointments

• Director for Center of Excellence in NanoBiophysics, 2006 –