Education:
BS Biology - Shihezi University, China
PhD 1992 Molecular Biology & Biochemistry - University of California, Davis
Postdoctoral Research Fellowship:
1994 - 1999 Harvard University, Cambridge, Massachusettes
Started at USC: 2004 Research Topics: Cancer, Virology, Immune defense, DNA/RNA enzymes, Protein Motors, Structural Biology
Research Description My research focuses on
- Cancer biology, with emphasis on cell growth regulation through oncogenes, tumor suppressors, and DNA/RNA modifying enzymes (deaminases, helicases, polymerases);
- 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;
- how oncogenes regulate tumor suppressors (such as hDlg, p53, pRB, etc) to promote cell transformation.
- 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.
10 Selected Publications:
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Shi Y,Liu H,Gai D,Ma J,Chen XS - A computational analysis of ATP binding of SV40 large tumor antigen helicase motor. - PLoS Comput Biol [2009] Sep;5(9):e1000514 PubMed
Ahuja D,Rathi AV,Greer AE,Chen XS,Pipas JM - A structure-guided mutational analysis of simian virus 40 large T antigen: identification of surface residues required for viral replication and transformation. - J Virol [2009] Sep;83(17):8781-8 PubMed
Bransteitter R,Prochnow C,Chen XS - The current structural and functional understanding of APOBEC deaminases. - Cell Mol Life Sci [2009] Jun 23;(): PubMed
Liu H,Shi Y,Chen XS,Warshel A - Simulating the electrostatic guidance of the vectorial translocations in hexameric helicases and translocases. - Proc Natl Acad Sci U S A [2009] Apr 21;(): PubMed
Chiang AN,Valderramos JC,Balachandran R,Chovatiya RJ,Mead BP,Schneider C,Bell SL,Klein MG,Huryn DM,Chen XS,Day BW,Fidock DA,Wipf P,Brodsky JL - Select pyrimidinones inhibit the propagation of the malarial parasite, Plasmodium falciparum. - Bioorg Med Chem [2009] Jan 20;(): PubMed
Brewster AS,Wang G,Yu X,Greenleaf WB,Carazo JM,Tjajadia M,Klein MG,Chen XS - Crystal structure of a near-full-length archaeal MCM: functional insights for an AAA+ hexameric helicase. - Proc Natl Acad Sci U S A [2008] Dec 23;105(51):20191-6 PubMed
Orrú V,Tsai SJ,Rueda B,Fiorillo E,Stanford SM,Dasgupta J,Hartiala J,Zhao L,Ortego-Centeno N,D'Alfonso S,Italian Collaborative Group,Arnett FC,Wu H,Gonzalez-Gay MA,Tsao BP,Pons-Estel B,Alarcon-Riquelme ME,He Y,Zhang ZY,Allayee H,Chen XS,Martin J,Bottini N - A loss-of-function variant of PTPN22 is associated with reduced risk of systemic lupus erythematosus. - Hum Mol Genet [2009] Feb 1;18(3):569-79 PubMed
Holden LG,Prochnow C,Chang YP,Bransteitter R,Chelico L,Sen U,Stevens RC,Goodman MF,Chen XS - Crystal structure of the anti-viral APOBEC3G catalytic domain and functional implications. - Nature [2008] Nov 6;456(7218):121-4 PubMed
Fletcher RJ,Shen J,Holden LG,Chen XS - Identification of amino acids important for the biochemical activity of Methanothermobacter thermautotrophicus MCM. - Biochemistry [2008] Sep 23;47(38):9981-6 PubMed
Thomas M,Dasgupta J,Zhang Y,Chen X,Banks L - Analysis of specificity determinants in the interactions of different HPV E6 proteins with their PDZ domain-containing substrates. - Virology [2008] Jul 5;376(2):371-8 PubMed
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