Yoo, Joo-Yeon, Ph.D.

Associate Professor
Department of Life Science
Division of Molecular and Life Sciences
Molecular Genomics and Immunology

Profile |  Research Interests |  Selected Publications

Profile

Research Interests

My research team focuses on understanding the global transcription network that governs the innate immune response of the body, eventually to develop novel diagnostic and therapeutic tools for inflammation-related diseases.

In higher metazoans, innate immune responses are initiated by chemical structures that are presented by invading microorganisms or revealed by damage to the host, and executed by inflammatory cytokines that modulate expression of loads of immune molecules. This general inflammation keeps us alive until the adaptive immune system produces specific weapons like antibodies to fight off germs or other invaders. Under an emergency state of the body, it takes a whole host of molecules to respond to the initial infection, but that response can be lethal if its regulation goes wrong. This regulation is mainly achieved by multiple transcription factors that are activated by signal transduction pathways of inflammatory cytokines during the innate immune response.

Having turned to microarray technology to profile the genes affected by bacterial infection in the liver, we uncovered an extensive metabolic adjustments that include suppression of synthesis pathways for fatty acid, phospholipids, and cholesterol, accompanied by coordinate induction of genes with direct roles in defense and immunity or intracellular signaling. It suggests that there are global levels of allocation of the transcription machinery from promoter regions of the metabolism-related genes to the defense-related genes during systemic inflammation. To understand the molecular mechanism of coordinated global gene regulation during bacterial infection, we are now investigating the role of the mammalian PAF complex during inflammation. We have recently found that the mammalian PAF complex specifically controls the expression of acute phase proteins, which mediate systemic inflammation of the body. In Saccharomyces cerevisiae, the PAF complex associates with the elongating RNA Polymerase II and is required for histone H3 methylation, therefore linking transcriptional elongation to chromatin modification. The in vivo and in vitro function of this complex is studied in the hepatocyte culture and mice, with gene targeting and transgenic strategies.

Specific interactions between transcription factors binding to their target sites provide specific features of gene regulation in a particular cellular content. Information about the structure of composite elements and gene regulation through such elements is extremely useful for prediction of a tissue-specific gene-expression pattern and responsiveness to known physiological signaling pathways, and eventually for applied gene engineering. Our research team focuses on the structural features of the promoter regions of the acute phase proteins. It is possible to predict and reconstruct physiological information, based on the genetic information encoded in the regulatory regions of the genes. Systemic inflammation is the perfect biological system to design and test various prediction algorithms, since it involves tons of genes that are coordinately regulated by multiple transcription factors. Through the combined approaches of computational biology and functional genomics, we wish to ultimately understand the gene-regulatory network of systemic inflammation.

Coordinated gene regulation during systemic inflammation. On the site of infection or injury, infiltrated immune cells are activated and secrets proinflammatory cytokines. These cytokines then activate transcription factors, such as Stat3, NFkB, or C/EBP, and cooperatively regulate gene expressions of acute phase proteins in the liver. Over 7% of total mouse genome was mobilized by bacterial protein, LPS.

Selected Publications

1. Kim, M.J., Yoo, J.-Y. Inhibition of hepatitis C virus replication by IFN-mediated ISGylation of HCV-NS5A. J Immunol. 185(7):4311-8. (2010)
2. Oh, Y.M., Kim, J.K., Choi, Y., Choi, S., Yoo, J.-Y. Prediction and experimental validation of novel STAT3 target genes in human cancer cells. PLoS One. 4(9):e6911. (2009)
3. Kim, M.J., Yoo, J.-Y. Active caspase-1-mediated secretion of retinoic acid inducible gene-I. J Immunol. 181(10):7324-31. (2008)
4. Kim, M.J., Hwang, S.Y., Imaizumi, T., Yoo, J.-Y. Negative feedback regulation of RIG-I-mediated antiviral signaling by interferon-induced ISG15 conjugation. J Virol. 82(3):1474-83. (2008)
5. Youn, M.Y., Yoo, H.S., Kim, M.J., Hwang, S.Y., Choi, Y., Desiderio, S.V., Yoo, J.-Y. hCTR9 a component of Paf1 complex, participates in the transcription of interleukin 6-responsive genes through regulation of STAT3-DNA interactions. J Biol Chem. 282(48):34727-34. (2007)  

Division of Molecular & Life Sciences| POSTECH