报告人：  Yanming Wang  Ph.D.

Assistant Professor, Department of Biochemistry and Molecular Biology,  Penn State University

时间：2009年6月30日（星期二）上午10：00

地点：中心实验楼502会议室

　　Our lab studies histone modifications in chromatin structure and function.  Recently, we found that the peptidylarginine deiminase 4 (PAD4) works as a transcriptional corepressor for the expression of p53-target genes, such as p21 and OKL38.  By designing inhibitors to target PAD4, we hope to offer new therapeutic treatments of cancers.  Moreover, PAD4 functions as an innate immune factor in neutrophils during bacterial infection.  Histone Arg citrullination catalyzed by PAD4 facilitates the release of chromatin to extracellular space to form a structure termed neutrophil extracellular traps that trap and kill bacteria.  Our research thus implicates PAD4 as a good cop in fighting bacteria but a bad cop in tumorigenesis by repressing tumor suppressor gene expression.

Publications （selected）:

　　1. Wang Y, Li M, Stadler S, Correll S, Li P, Wang D, Hayama R, Leonelli L, Han H, Grigoryev S,Allis CD, Coonrod SA (2009) Histone hypercitrullination mediates chromatin decondensationand neutrophil extracellular trap formation. J of Cell Biol. 184:205-13.

　　2. Hao G, Wang D, Gu J, Shen Q, Gross SS, and Wang Y. (2009) Neutral loss of isocyanic acid inpeptide CID spectra: a novel diagnostic marker for mass spectrometry identification of protein citrullination. J Am Soc Mass Spectrom. (Epub Dec. 30, 2008)

　　3. Li P, Yao H, Zhang Z, Li M, Luo Y, Thompson PR, Gilmour DS, Wang Y. (2008) Regulation of p53 target gene expression by peptidylarginine deiminase 4. Mol and Cell Biol. 28, 4745-58.

　　4. Yao H, Li P, Venters BJ, Zheng S, Thompson PR, Pugh BF, Wang Y. (2008) Histone Arg modifications and p53 regulate the expression of OKL38, a mediator of apoptosis. J Biol Chem. 283, 20060-8.

　　5. Wang, Y., Wysocka J., Sayegh, J., Lee, Y.H., Perlin J.R., Leonelli, L., Sonbuchner, L.S., McDonald, C.H., Cook, R.G., Dou, Y., Roeder, R.G., Clarke, S., Stallcup, M.R., Allis, C.D.,Coonrod, S.A. (2004) Human PAD4 regulates histone arginine methylation levels via demethylimination. Science 306, 279-83.

　　6. Wang, Y., Zhang, W., Jin, Y., Johansen, J., and Johansen, K.M. (2001) The JIL-1 tandem kinase mediates histone H3 phosphorylation and is required for maintenance of chromatin structure in Drosophila. Cell 105: 433-43.

　　

　　北京大学人类疾病基因研究中心

　　2009.6.26