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 Cell Biology, Virology, Immunology, Structural Biology
Research Description
Xiaojiang Chen's combined expertise in molecular biology, biochemistry and X-ray crystallography enables him to study important biological questions at molecular level. He has done landmark work on tumor viruses and viral oncogenes. His current studies focus on the cell growth regulated by tumor viruses, and the immune responses to viral infections.
We are interested in the fundamental mechanisms of how normal cells are turned into cancerous ones (oncogenesis), and how immune system responds to foreign antigens through B cell activation. Four active areas of research are going in the lab now.
1. How cell growth cycle is regulated through viral oncogenes.
Tumor viruses use oncoproteins to transform normal cells into cancerous cells. Among such oncogenes are large Tumor antigen (LTag) from SV40, E6 and E7 from papillomavirus, and E1A from Adenovirus. We want to understand how these diverse group of oncoproteins regulate cellular targets to promote the uncontrolled cell growth as in tumors. The detailed knowledge of cell growth control by the oncoproteins will help the development of anti-cancer therapy.
2. How DNA replication is regulated through helicases.
An important class of helicases is ring-shaped hexamers or double-hexamers. They control DNA replication at the replication origin and forks. Two of such helicases are MCM (mini-chromosome maintenance)and LTag. The cellular helicase MCM plays a vital role in making sure the DNA is duplicated only once per cell cycle. Over- or under-replication results in genomic instability and leads to cancer. We study the mechanism of how replicative helicases regulate DNA replication.
3. How hexameric helicases unwind double helix DNA
The helicases for replication are efficient molecular machine for unwinding long stretches of dsDNA. How these molecular machines use ATP as the energy source to do the mechanical work of unwinding dsDNA is a fascinating question. We want to address this interesting question by studying these various ring-shpaed helicases in their different functional states.
4. How the immune system responds to foreign antigens through B-cell activation.
Antibody (humoral) response via B cells is important for our immune defense against foreign infection and a B cell surface receptor, CR2 or CD21, is critical for this process. CR2/CD21 can sense foreign antigens through its interactions with a complement factor C3d, and such interactions generate signals for B cell activation, leading to clonal amplification and specific antibody production by B cells. We want to understand the mechanisms of B cell activation centered around the receptor of CR2/CD21.
Selected Publications
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 ] Apr 29; . PubMed
Greenleaf WB, Shen J, Gai D, Chen XS. - A SYSTEMATIC STUDY OF THE FUNCTIONS FOR THE RESIDUES AROUND THE NUCLEOTIDE POCKET IN SV40 AAA+ HEXAMERIC HELICASE. - J Virol [ 2008 ] Apr 9; . PubMed
Wang G, Klein MG, Tokonzaba E, Zhang Y, Holden LG, Chen XS. - The structure of a DnaB-family replicative helicase and its interactions with primase. - Nat Struct Mol Biol [ 2008 ] Jan;15(1):94-100 . PubMed
Chen P, Jiang M, Hu T, Liu Q, Chen XS, Guo D. - Biochemical characterization of exoribonuclease encoded by SARS coronavirus. - J Biochem Mol Biol [ 2007 ] Sep 30;40(5):649-55 . PubMed
Young KA, Chen XS, Holers VM, Hannan JP. - Isolating the Epstein-Barr virus gp350/220 binding site on complement receptor type 2 (CR2/CD21). - J Biol Chem [ 2007 ] Dec 14;282(50):36614-25 . PubMed
Bishop B, Dasgupta J, Klein M, Garcea RL, Christensen ND, Zhao R, Chen XS. - Crystal structures of four types of human papillomavirus L1 capsid proteins: understanding the specificity of neutralizing monoclonal antibodies. - J Biol Chem [ 2007 ] Oct 26;282(43):31803-11 . PubMed
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. - Proc Natl Acad Sci U S A [ 2007 ] Jul 31;104(31):12685-90 . PubMed
Knappe M, Bodevin S, Selinka HC, Spillmann D, Streeck RE, Chen XS, Lindahl U, Sapp M. - Surface-exposed amino acid residues of HPV16 L1 protein mediating interaction with cell surface heparan sulfate. - J Biol Chem [ 2007 ] Sep 21;282(38):27913-22 . PubMed
Zhang Y, Dasgupta J, Ma RZ, Banks L, Thomas M, Chen XS. - Structures of a human papillomavirus (HPV) E6 polypeptide bound to MAGUK proteins: mechanisms of targeting tumor suppressors by a high-risk HPV oncoprotein. - J Virol [ 2007 ] Apr;81(7):3618-26 . PubMed
Bishop B, Dasgupta J, Chen XS. - Structure-based engineering of papillomavirus major capsid l1: controlling particle assembly. - Virol J [ 2007 ] Jan 8;4:3 . PubMed
