Home > Research Institute > Departments > Department of Bioscience and Genetics

Department of Bioscience and Genetics

Members

Staff Scientists Masahiko Honda, Ph.D.

Research Topics

We are studying on the structure and function of the human genes and gene products using molecular and biochemical techniques to define the molecular pathogenesis of cardiovascular diseases. Our researches include the following topics.

Molecular Study of Cardiac Development

Molecular mechanism of cardiac development has not been well characterized compared with that of skeletal muscle development. To better understand molecular basis of cardiac development, we are studying molecules regulating cardiomyocyte differentiation by utilizing cellular models.

Although no good cellular model for cardiomyocyte differentiation is not available, embryonic stem cells (ES cells) are known to differentiate into various cell types including self-contracting cardiomyocytes. Therefore, we are trying to establish better cellular models for cardiomyocyte differentiation. Also we are trying to isolate and identify transcription factors and signaling molecules controlling cardiomyocyte differentiation. Since ES cells can be utilized to produce genetically engineered whole animal, we are going to perform functional analysis of the newly identified molecules in vivo. As an application of understanding molecular mechanism of cardiac development, in vivo experiments of cardiac regeneration are also being performed.

Ref)
  1. Kim HS, Hidaka K, Morisaki T: Expression of ErbB receptors in ES cell-derived cardiomyocytes. Biochem Biophys Res Commun 309:241-246, 2003.
  2. Hidaka K, Lee JK, Kim HS, Ihm CH, Iio A, Ogawa M, Nishikawa SI, Kodama I, Morisaki T: Chamber-specific differentiation of Nkx2.5-positive cardiac precursor cells from murine embryonic stem cells. FASEB J 17:740-742, 2003.
  3. Iio A, Koide M, Hidaka K, Morisaki T: Expression pattern of novel chick T-box gene, Tbx20. Dev Genes Evol 211:559-562, 2001

Genetic Study of Cardiovascular Diseases

Completion of Human Genome Project opens a door for us to understand genetic backbone for pathogenesis of cardiovascular diseases. We are trying to identify disease susceptibility genes for cardiovascular diseases.

We are utilizing genetic information including genetic variations such as single nucleotide polymorphisms (SNPs) to identify disease responsive genes, aiming to create newer therapeutic approach for cardiovascular diseases in the future. Currently we are analyzing SNPs for their variations among different populations to characterize the specific information of SNPs in Japanese.

Ref)
  1. Mizuguchi T, Collod-Beroud G, Akiyama T, Abifadel M, Harada N, Morisaki T, Allard D, Varret M, Claustres M, Morisaki H, Ihara M, Kinoshita A, Yoshiura K, Junien C, Kajii T, Jondeau G, Ohta T, Kishino T, Furukawa Y, Nakamura Y, Niikawa N, Boileau C, Matsumoto N: Heterozygous TGFBR2 mutations in Marfan syndrome. Nat Genet 36:855-860, 2004.
  2. Morisaki H, Nakanishi N, Kyotani S, Takashima A, Tomoike H, Morisaki T: BMPR2 mutations found in Japanese patients with familial and sporadic primary pulmonary hypertension. Hum Mut 23:632, 2004.
  3. Ito T, Chiku S, Inoue E, Tomita M, Morisaki T, Morisaki H, Kamatani N: Estimation of haplotype frequencies, linkage-disequilibrium measures, and combination of haplotype copies in each pool by use of pooled DNA data. Am J Hum Genet 72:384-398, 2003

Molecular Study of Nuleotide Metabolism in Cardiovacular Sytem

Nulceotide metabolism plays important roles not only for producing sources of DNAs and RNAs but also for many aspests of cellular function via adenosine, ATP and GTP etc. In addition, AMP-activated protein kinase has been shown an important regulator of diverse cellular pathways in many types of cells including heart. In particular, functional analysis of AMP metabolism are being performed by using various molecular techniques including creation of gene knock-out mice.

Ref)
  1. Toyama K, Morisaki H, Kitamura Y, Gross M, Tamura T, Nakahori Y, Vance JM, Speer M, Kamatani N, Morisaki T: Haplotype Analysis of Human AMPD1 Gene. Origin of Common Mutant Allele. J Med Genet 41:e74, 2004.
  2. Tomikura Y, Hisatome I, Tsuboi M, Yamawaki M, Shimoyama M, Yamamoto Y, Sasaki N, Ogino K, Igawa O, Shigemasa C, Ishiguro S, Ohgi S, Nanba E, Shiota G, Morisaki H, Morisaki T, Kitakaze M: Coordinate induction of AMP deaminase in human atrium with mitochondrial DNA deletion. Biochem Biophys Res Commun 302:372-376, 2003.

Production and Study of Genetically Modified Animals

Transgenesis is useful for understanding of biological mechanisms and producing disease models that allow new therapies to be developed and tested. We use this technique to elucidate the mechanisms of the heart development and produced some transgenic models to develop new therapy for cardiovascular diseases.

Ref)
  1. Kuwahara K, Saito Y, Takano M, Arai Y, Yasuno S, Nakagawa Y, Takahashi N, Adachi Y, Takemura G, Horie M, Miyamoto Y, Morisaki T, Kuratomi S, Noma A, Fujiwara H, Yoshimasa Y, Kinoshita H, Kawakami R, Kishimoto I, Nakanishi M, Usami S, Saito Y, Harada M, Nakao K.: NRSF regulates the fetal cardiac gene program and maintains normal cardiac structure and function. EMBO J. 22: 6310-6321, 2003.
  2. Iwata Y, Katanosaka Y, Arai Y, Komamura K, Miyatake K, Shigekawa M.: A novel mechanism of myocyte degeneration involving the Ca2+-permeable growth factor-regulated channel. J. Cell Biol. 161: 957-967, 2003.
  3. Yatsuki H, Joh K, Higashimoto K, Soejima H, Arai Y, Wang Y, Hatada I, Obata Y, Morisaki H, Zhang Z, Nakagawachi T, Satoh Y, Mukai T.: Domain regulation of imprinting cluster in Kip2/Lit1 subdomain on mouse chromosome 7F4/F5: large-scale DNA methylation analysis reveals that DMR-Lit1 is a putative imprinting control region. Genome Res. 12: 1860-1870, 2002.
  4. Soejima H, Kawamoto S, Akai J, Miyoshi O, Arai Y, Morohka T, Matsuo S, Niikawa N, Kimura A, Okubo K, Mukai T.: Isolation of novel heart-specific genes using the BodyMap database. Genomics 74: 115-120, 2001.
Page Top