Login

 


Plenary Lecture

Systems Molecular Medicine for Cancer Metastasis and Drug Discovery

Professor Hiroshi Tanaka
Department of Bioinformatics
Medical Research Institute
Tokyo Medical and Dental University
Japan
E-mail: tanaka@bioinfo.tmd.ac.jp

Abstract: Epithelial-mesenchymal transition (EMT) is now widely recognized as the cause of cancer invasion and metastasis. From the dynamical systems view of the cellular molecular network, it is considered that each cell type represents the stable state of cellular molecular network which could be thought as a basin located in the epigenetic landscape, separated by “epigenetic barrier”. Thus, EMT could be considered as global “phase transition” of transcription network from the stable cellular network state of epithelial cell to that of mesenchymal cell. We developed a new method which can depict this epigenetic landscape quantitatively based on the statistics of fluctuation of the gene expression. To depict the EMT process on the epigenetic landscape, we conducted the experimental observation of temporal change of gene expression profile during EMT of retinal pigment epithelium cell line (ARPE-19) caused by TGF-beta and TNF-alpha. The ARACNe algorithm was used to infer structural change of gene regulatory network of about 4000 genes. The results showed that in the initial stage, keratin (KRT18) and e-cadherin (EDH1) are active, while TWIST1/2, ZEB1 and TCF3 start to globally regulate EMT process, and in final stage, messenchymal marker such as CD44 and COL1A are expressed. The global cooperative change of gene expression pattern was observed to suggest that the collective structural change of molecular network is taking place during EMT process which can be depicted on the quantitative epigenetic landscape.
Furthermore, the network hierarchical structure of protein interaction networks (PIN) and their relationship with lethal genes and possible drug targets was studied, so that the statistical likelihood of novel drug targets could be inferred. Our study revealed “three-layer structure” of PIN, and middle-layer nodes compose the backbone of PIN. Drug-target molecules are distributed with higher probability on middle degree layer. While the average degree of targets for cancer drugs was 7.82, the targets for non-cancerous diseases scored only 4.24 (p = 0.01). The reason is considered that, cancer is contracted mostly after reproduction period so that evolutional process has not eliminated cancer disease genes.

Brief Biography of the Speaker: Prof. Tanaka obtained a BS and MS degree from Mathematical Engineering, University of Tokyo (Japan), in 1974 and 1976, respectively. He got Dr. Med. from graduate school of medicine, University of Tokyo, in 1981 and Ph.D. in computer science from graduate school of engineering, University of Tokyo, in 1983. He was installed as an assistant professor of medicine, University of Tokyo in 1982. He was a visiting scientist at MIT laboratory of computer science during 1990. He was installed as a professor of bioinformatics, Medical Research Institute, Tokyo Medical and Dental University in 1991. He was the director of Information Center for Medicine in Tokyo Medical and Dental University from 1995-2010. He was Dean of School of Biomedical Science from 2006 to 2010. He worked as the president of Japan Association of Medical Informatics from 2003-2007. He is now chairman of Chem-Bioinformatics association and also that of the Japan association of Omics-based medicine, acting as one of the leaders of genomic medicine and translational bioinformatics in Japan.

Bulletin Board

Currently:

The conference program is online.

The Conference Guide is online.

The paper submission deadline has expired. Please choose a future conference to submit your paper.


WSEAS Main Site


NAUN Main Site

Publication Ethics and Malpractice Statement