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

 

1.	Prochnow C, Bransteitter R, Klein M, Goodman M, Chen X. The APOBEC2 Crystal Structure and the Functional Implications for AID Activity and Mutations in Hyper-IgM Patients. NATURE (2006) in press.
2.	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.
3.	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. BIOLOGY ( 2006) 13:996-1001
4.	Shen J, Gai D, Patrick A, Greenleaf WB, Chen X. The roles of the residues on the channel b-hairpin and loop structures of simian virus 40 hexameric helicase. PNAS. (2005) 102:11248-53.
5.	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 119:47-60 (2004)
6.	Sclafani, Robert. Fletcher, C. Ryan. and Chen, X. Two Heads Are Better Than One: Regulation of DNA replication by double-hexameric helicases GENES & DEV. (2004) 18:2039-2045.
7.	Gomez-Lorenzo,M. Valle,M. Frank,J. Gruss,C. Sorzano,C. Chen, X. Carazo, JM. Large T antigen on the simian virus 40 origin of replication: a 3D snapshot prior to DNA replication. EMBO J. (2003) 1;22(23):6205-13
8.	Li, D. Zhao, R. Lilyestrom, W. Dahai Gai, D. Zhang, R. DeCaprio, J. Fanning, E. Szakonyi, G and Chen, X. The Structure of the Replicative Helicase of the Transforming Protein SV40 Large T-antigen. NATURE. (2003) 423, 512-518
9.	Fletcher RJ, Bishop BE, Leon RP, Sclafani RA, Ogata CM, Chen X. The structure and function of MCM from archaeal M. Thermoautotrophicum. NATURE STRUCTURAL BIOL. (2003) 10,160-167
10.	Boackle S., Holers M., Chen X., Szakonyi G., Karp D, Wakeland E and Morel L. Cr2, a candidate gene in the NZM2410 Sle1c lupus susceptibility locus, encodes a dysfunctional protein. IMMUNITY, (2001) 15, 729-738.
11.	Szakonyi G, Guthridge J, Li D, Young K, Holers M, Chen X. Structure of Complement Receptor Type 2 in Complex with Its Ligand C3d. SCIENCE. (2001) 292, 1725-1728
12.	Chen X, Garcea R, Goldberg I, Casini G, Harrison C. Crystal Structure of Human Papilloma Virus T1 Particles of the Major Capsid L1 MOL. CELL. (2000) 5, 557-567