Division of Molecular and Genomic Medicine
Introduction
Since 1996, the Division of Molecular and Genomic Medicine (MGM Division) was established to introduce newly emerging molecular and genetic techniques to meet the challenges of medical research of the 21st century. Its mission is to develop outstanding research programs to better understand molecular and genetic basis of diseases prevalent in Taiwan, with eventual goals to provide strategies for detection and therapy.
There are three phases of the programs: the first is the gene-discovery phase, where using the state-of-art technology, the Division will try to identify genes that are altered in structure or expression in disease tissues of various stages; the second is gene-function phase, where the functions of the disease-related genes will be studied to provide an understanding of their roles in disease development. Finally, gene-application phase, where the mechanism of disease development is appreciated, and the possible molecular markers and therapeutic targets are identified. The Program integrates well with the goals of the other divisions at NHRI, such Cancer Research, Biotechnology and Pharmaceutical Research, Clinical Research, and Biostatistics & Bioinformatics Research, etc. The Division has been collaborating extensively with a number of laboratories around the nation. It is the Division's strong belief that through teamwork and concerted efforts, they will be able to make a significant impact on prevalent diseases in Taiwan.
Broadly there are two approaches MGM Division are taking to discover disease-related genes. The first one is by genetic-mapping, such as the use of polymorphic marker scanning to identify altered loci, with eventual objective of identifying the disease susceptibility genes involved. The second approach is by molecular profiling, such as the use of differential display, cDNA microarray analysis, subtractive cDNA analysis to identify differentially expressed genes. Through these efforts, genes altered in structure and expression can be identified. Once identified, the Division's focus will be in growth regulations, such as kinases and signaling components. Several interesting and previously unknown kinases have already been identified. The functional studies of these genes are on the way to understand their possible roles in the development and progression of nasopharyngeal and liver cancer cells.
Organization chart
Major Research Activities
Programmatic Objectives (long-term):
To develop and bring in state-of-the-art molecular and genetic technologies and research activities to identify genes and molecular mechanisms involved in diseases prevalent in Taiwan. To facilitate the integrated research efforts of NHRI by working closely together with other divisions, rapidly disseminating the laboratory findings and providing molecular and genetic expertise. To promote health-related molecular and genetic research in Taiwan by serving as a resource and by collaborating with other investigators in a complementary and synergistic way.
Scientific Objectives (short-term):
- To use various genome mapping and scanning approaches to identify genes altered in nasopharyngeal and liver cancers.
- To use various molecular profiling and cDNA expression approaches to identify genes related to nasopharyngeal and liver cancers.
- To study the growth and oncogenic signal pathways involved in the development and progression of nasopharyngeal and liver cancers
Program Outline
-
Gene-discoveries: Two approaches are being
taken; one genetic and the other molecular,
with the eventual objectives to identify
structurally altered or differentially
expressed genes.
- Genomic mapping and scanning.
- Molecular profiling and differential gene expression.
-
Gene-functions: Once the disease-related genes
are identified, the Division will disseminate
the information to other divisions, and then
select those molecules involved in signal
transduction and cell cycle control for further
functional analysis.
- Protein kinases and signal transduction.
- Cell-cycle and transcriptional regulators
-
Gene-applications: This phase most likely will
be carried out with other divisions, including
the Biotechnology and Pharmaceutical Research,
Cancer Research and Clinical Research
Divisions.
- Diagnostic and prognostic markers.
- Therapeutic targets and drug discoveries
Gene Discovery Group:
In the gene discovery group, microarray analysis (Cancer EST Project) and chromosome mapping (ATGC Project) are used to identify putative genes that may play important roles in growth control and/or tumor progression of human hepatoma and nasopharyngeal cancer cells.
Teamwork:- Dr. Yuh-Shan Jou: Chromosome Mapping
- Dr. Chen-Kung Chou: Microarray Analysis
- Dr. Shih-Feng Tsai: Genome Analysis
Functional Study Group:
In the functional study group, yeast two-hybrid, mouse genetics, Xenopus mitotic control, and Drosophila system, are employed to explore the function of novel gene discovered by the gene discovery team in each model system. Principal investigators in functional study group will carry out their own research project on characterization of function of important molecular targets in different biological systems.
Teamwork:- Dr. Hsiu-Ming Shih: ETK/MST4, Protein Networks of Cancer Associated Genes, Yeast Array, Novel Technologies in Drug Discovery
- Dr. Jyh-Lyh Juang: Drosophila Ab1, Microarray Analysis
- Dr. Chi-Ying F. Huang: Apoptosis / Cell Cycle Regulation / Proteolytic Control
- Dr. King-Song Jeng: HBV/HCV Hepatoma
NHRI Cancer EST (Expressed Sequence Tag) Project
Hepatocellular carcinoma (HCC) is one of the most common forms of human cancer. It is prevalent in Asia where hepatitis B (HBV) and hepatitis C virus (HCV) infectious are rampant. In order to control HCC in the future, we need to understand more about the alteration of human liver gene expression profile during the progression of HCC. The advancement of technologies, such as gene mapping / sequencing and the initiation of the human genome project in 1990, as well as the expressed sequence tag (EST) sequencing effort launched by Merck/Washington University in 1994 have completely changed the landscape of disease gene discovery.
In Taiwan, two different approached are used to investigate genetic alterations of HCC. One is employing the loss of heterozygosity (LOH) and comparative genome hybridization (CGH) analysis to identify disease locus and to start genomic sequencing of these HCC associated loci. The other one is to establish an EST database on human liver, which is still not available in public domain. In this approach, seven human cDNA libraries were prepared from one normal adult liver tissue and three paired hepatoma tissues. Total 5,615 EST sequences were then combined with 128,162 liver related EST sequences from NCBI UniGene database. After organizing blast results of all these EST sequences, two electronic differential display profile tables were created. The Division hopes that these results will provide a useful resource (http://lestdb.nhri.org.tw) to promote the HCC researches in Taiwan and the whole world.
ATGC (Applied Taiwan Genotyping Consortium)
Applied Taiwan Genotyping Consortium (ATGC) is aimed to establish a nationwide network by requesting proposals to form a genotyping consortium and to collect reference genomic DNA for studying genetic components of common diseases in local populations. In addition, ATGC will promote sharing of genotyping technologies and resources. The genotyping data on reference genomic DNA to our population will expand the information of polymorphic markers in TPMD (Taiwan Polymorphic Marker Database; http://tpmd.nhri.org.tw). In the post-genomic era, the ATGC organized by the MGM division will allow scientists to better understanding the molecular and genetic basis of diseases prevalent in Taiwan.
Interaction among the MGM Teams
