Department of Bioinformatics and Molecular Neuropathology
Meiji Pharmaceutical University
Following the completion of the Human Genome Project in 2003, we now could
clarify the comprehensive profile of all human genes expressed in specific
subsets of the cell by using DNA microarray. The global analysis of transcriptome,
along with proteome, has greatly facilitated the genome-based drug discovery
research aimed at mining the best molecular target for the rational drug
design from huge numbers of disease-related and drug-responsive genes.
Multiple sclerosis (MS) is an inflammatory demyelinating disease of unknown
etiology that affects exclusively the human central nervous system white
matter. By using DNA microarray, we have recently studied gene expression
profile of T lymphocytes of MS patients and healthy controls, and from
MS patients in relapse and during remission. We found a set of differentially
expressed genes between MS and healthy subjects, and between acute relapse
and complete remission. Hierarchical clustering analysis of the discriminator
genes established classification of MS subgroups exhibiting distinct gene
expression profiles and relapse-specific molecular signatures. By using
KeyMolnet, a novel data-mining tool of bioinformatics, we identified the
principal molecular network involved in development of MS and induction
of acute relapse.
Prion diseases are an intractable neurodegenerative disease of animals
and humans mediated by an abnormal prion protein (PrPSc). The protein conformational
conversion from PrPC to PrPSc requires an as
yet unidentified species-specific auxiliary factor named ügProtein Xüh. By using
protein microarray, we identified a set of novel PrPC interactors as the
candidate for Protein X. Because the network of PrPC
and interactors involves signaling pathways essential for regulation of
cell survival, differentiation, proliferation and apoptosis, our observations
proposed a logical hypothesis that dysregulation of
the PrPC interactome could induce extensive neurodegeneration in prion
diseases. Thus, molecular network analysis is a valuable approach to extract
biological implications from massive array data.
Professor Jun-ichi Satoh, M.D., Ph.D.