Chen, Xiaojiang - University of Southern California

研究领域

My research focuses on 1) Cancer biology, with emphasis on cell growth regulation through oncogenes, tumor suppressors, and DNA/RNA modifying enzymes (deaminases, helicases, polymerases); 2) Immune regulation (B, T cells) and host innate and acquired immune defenses against viruses (HIV, HPV, EBV). Cancer, immune disorder (autoimmunity), and other human diseases can be caused by disruption of normal cellular processes, which can be resulted from somatic mutations, or be caused by viral infections (such as HPV, HCV, HIV). My laboratory studies the molecular mechanisms of the key cellular and viral proteins involved in oncogenesis and immune defenses. In cancer biology, understanding cell growth control is critical for effective therapy for cancer and other related diseases. We study cell growth control from two angles; (1) how oncogenes regulate tumor suppressors (such as hDlg, p53, pRB, etc) to promote cell transformation. (2) how polymerase/primase and the ring-shaped helicases, which are efficient protein motors, control DNA replication and cell growth. In immune defenses, APOBEC3G, a member of APOBEC deaminase family causing C-to-U mutation, is a potent innate immunity against HIV/HBV viruses. We study APOBEC3G and develop its anti-HIV activity as an anti-AIDS therapy. In the acquired immune defenses, we study both the initial antibody (humoral) response mediated via B-cell signaling and the subsequent antibody maturation through somatic hypermutation by another APOBEC deaminase, AID. We also study the T cell immune responses regulated by protein tyrosine phosphotases (PTP). Our research tools include the powerful technology, X-ray crystallography, as well as functional biochemistry, molecular biology, cell biology, biophysics, and other biological methods.

近期论文

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Chang Y, Xu M, Machado C, Yu X, Rohs R, Chen XS. Origin DNA Recognition by the SV40 Large Tumor Antigen: Insights into the Mechanism of Initiator Assembly. Cell Reports 2013, 3(4):1117-27 Slaymaker I, Fu Y, Toso D, Ranatunga N, Brewster A, Forsburg S, Zhou H, Chen XS. Mini-chromosome Maintenance Complexes Form A Filament To Remodel DNA Structure and Topology. Nucleic Acid Research 2013 41(5):3446-56. Patrick A, Cabrera J, Chen XS, Ford H, Zhao R. Crystal Structure of the Transcriptional Complex SIX1/EYA That is Critically Involved in Organ Development and Tumorigenesis. Nature Struct Mol. Biol. 2013. 20(4):447-53. Gai D, Chang YP, Chen X. Mutational analysis of an archaeal minichromosome maintenance protein exterior hairpin reveals critical residues for helicase activity and DNA binding. Curr Opin Struct Biol. 2010 Dec;20(6):756-62. Epub 2010 Oct 1. Liu H, Shi Y, Chen X, Warshel A. Simulating the electrostatic guidance of the vectorial translocations in hexameric helicases and translocases. PNAS. (2009) 106(18):7449-54. Shi Y, Liu H, Gai D, Ma JP, Chen X. A Computational Analysis of ATP Binding of SV40 Large Tumor Antigen Helicase Motor. PloS Computational Biol 2009, 5 (9) 1-13. Holden L, Prochnow C, Chang YP, Bransteitter R, Stevens R, Goodman M, Chen X. Structure of the Anti-Viral APOBEC3G Catalytic Domain and Functional Implications. NATURE (2008), 6;456(7218):121-4. Brewster A, Wang G, Yu X, Greenleaf W, Carazo JM, Tjajadi M, Klein M, Chen X. Crystal structure of a near-full-length archaeal MCM: functional insights for an AAA+ hexameric helicase. PNAS (2008), 105(51):20191-6. Wang G, Klein MG, Tokonzaba E, Zhang Y, Holden LG, Chen X. The structure of a DnaB-family replicative helicase and its interactions with primase. NATURE STUCT MOL. BIOL. (2008) 15:94-100. Prochnow C, Bransteitter R, Klein M, Goodman M, Chen X. The APOBEC-2 crystal structure and functional implications for the deaminase AID. NATURE. (2007) 25;445(7126):447-51 Chang YP, Wang G, Bermudez V, Hurwitz J, Chen XS. - Crystal structure of the GINS complex and functional insights into its role in DNA replication. PNAS (2007) 104(31):12685-90 Lilyestrom W, Klein M, Zhang R, Joachimiak A, Chen X. Crystal structure of SV40 large T-antigen bound to p53: interplay between a viral oncoprotein and a cellular tumor suppressor. GENES & DEV. (2006) 20(17):2373-82. Szakonyi G, Klein M, Hannan J, Young K, Ma R, Asokan R, Holers M, Chen X. Structure of The Epstein Barr Virus Major Envelope Glycoprotein. NATURE STUCT MOL. BIOL. (2006) 13:996-1001. Shen, J. Gai, D. Patrick, A. Greenleaf, W. Chen, X. The Roles Of The Residues On The Channel .-Hairpin And Loop Structures Of SV40 Large T Hexameric Helicase. PNAS (2005) 102:11248-53. Gai, D. Zhao, R. Li, D. Finkielstein,C.V. and Chen, X. The Mechanisms of Conformational Change for A Replicative Hexameric Helicase of SV40 Large T Antigen. CELL (2004) 119:47-60. Sclafani, Robert. Fletcher, C. Ryan. and Chen, X. Two Heads Are Better Than One: Regulation of DNA replication by double-hexameric replicative helicases. GENES & DEV. (2004) 18:2039-2045. Li, D. Zhao,R. Lilyestrom,W. Gai,D. Zhang,R. Fanning,E. Szakonyi,G and Chen, X. The Structure of the Hexameri Replicative Helicase of SV40 Large Tumor antigen. NATURE. (2003) 423, 512-518. Fletcher R. J, Bishop B. E, Leon R. P, Sclafani R. A, Ogata C. M, Chen X. The structure and function of the MCM complex from archaeal M. Thermoautotrophicum. NATURE STRUCT. BIOL. (2003) 10,160-167. Boackle S, Holers M, Chen X, Szakonyi G, Karp D, Wakeland E and Morel L. Cr2, a gene in the NZM2410 Sle1c lupus susceptibility locus, encodes a dysfunctional protein. IMMUNITY (2001) 15, 729-738. Szakonyi G., Guthridge J., Li D., Young J. K., Holers M., Chen X. Structure of Complement Receptor Type 2 (CR2/CD21) in Complex with Its Cellular Ligand C3d. SCIENCE (2001) 292, 1725-1728.