Molecular Biology Section
Building 30, Room 407
30 Convent Dr MSC 4370
Bethesda, MD 20892-4370
The overall goal of the Molecular Biology Section is to discover novel molecular mechanisms that underlie the development of hard tissues and ectodermal organs by identifying novel functions of previously unstudied genes and defining the roles of the extracellular matrix (ECM). The laboratory has focused on the novel roles of protein factors and ECM components in proliferation, differentiation, and cell adhesion during development of teeth, cartilage, and other tissues. These studies are aimed at developing reagents useful for diagnostic and therapeutic applications. Most recently, Dr. Yamada’s group identified several novel proteins from a tooth germ cDNA library, including the transcription factor epiprofin, the adhesion protein fibulin7 (TM14), and the gap junction protein pannexin 3. These proteins are expressed in teeth as well as in tissues such as cartilage, bone, and skin. Identification of common and distinct molecular mechanisms for the function of these proteins in specific tissue types will uncover key concepts that underlie both normal development and disease.
Dr. Yoshihiko Yamada received a PhD from Osaka University Faculty of Science, Japan. After receiving his PhD, Dr. Yamada began postdoctoral training at the University of Pittsburgh, where he investigated gene regulation of bacteriophages and plasmids. In 1978, Dr. Yamada came to the National Cancer Institute (NCI) at NIH to study gene evolution and regulation of collagen genes. In 1983, he joined NIDCR, where he has been studying the functions of basement membrane components, cartilage matrices, and other extracellular matrices during development and diseases. Dr. Yamada is a recipient of a Young Investigator Research Grant from the University of Pittsburgh, as well as an NIH Director's Award, the CRADA, Eli Lilly and Company Award, a research grant from Seikagaku Corporation, the Debio Peptide Award, and the William J. Gies Award.
- Suzuki N, Fukushi M, Kosaki K, Doyle AD, de Vega S, Yoshizaki K, Akazawa C, Arikawa-Hirasawa E, Yamada Y. Teneurin-4 is a novel regulator of oligodendrocyte differentiation and myelination of small-diameter axons in the CNS. J Neurosci. 2012 Aug 22;32(34):11586-11599.
- Ishikawa M, Iwamoto T, Nakamura T, Doyle A, Fukumoto S, Yamada Y. Pannexin 3 functions as an ER Ca2+ channel, hemichannel, and gap junction to promote osteoblast differentiation. J Cell Biol. 2011 Jun 27;193(7):1257-1274.
- Matsunobu T, Torigoe1 K, Ishikawa1 M, de Vega S, Kulkarni AB, Iwamoto Y, Yamada Y. Critical roles of the TGF-β type I receptor ALK5 in perichondrial formation and function, cartilage integrity, and osteoblast differentiation during growth plate development. Dev Biol. 2009 Aug 15;332(2):325-338.
- Fukumoto S, Kiba T, Hall B, Iehara N, Nakamura T, Longenecker G, Krebsbach PH, Nanci A, Kulkarni AB, Yamada Y. Ameloblastin is a cell adhesion molecule required for maintaining the differentiation state of ameloblasts. J Cell Biol. 2004 Dec 6;167(5): 973-983.
- Arikawa-Hirasawa E, Le AH, Nishino I, Nonaka I, Ho NC, Francomano CA, Govindraj P, Hassell JR, Devaney JM, Spranger J, Stevenson RE, Iannaccone S, Dalakas MC, Yamada Y. Structural and functional mutations of the perlecan gene cause Schwartz-Jampel syndrome, with myotonic myopathy and chondrodysplasia. Am J Hum Genet. 2002 May;70(5): 1368-1375.
- Arikawa-Hirasawa E, Rossi SG, Rotundo RL, Yamada Y. Absence of acetylcholinesterase at the neuromuscular junctions of perlecan-null mice. Nat Neurosci. 5(2): 119-123.
- Arikawa-Hirasawa E, Wilcox WR, Yamada Y. Dyssegmental dysplasia, Silverman-Handmaker type: Unexpected role of perlecan in cartilage development. Amer J Med Genet. 2001 Winter;106:254-7.
- Arikawa-Hirasawa E, Wilcox WR, Le AH, Silverman N, Govindraj P, Hassell JR, Yamada Y. Dyssegmental dysplasia, Silverman-Handmaker type, is caused by functional null mutations of the perlecan gene. Nat Genet. 2001 Apr;27(4): 431-4.
- Tsumaki N, Tanaka K, Arikawa-Hirasawa E, Nakase T, Kimura T, Thomas JT, Ochi T, Luyten FP, Yamada Y. Role of CDMP-1 in skeletal morphogenesis: Promotion of mesenchymal cell recruitment and chondrocyte differentiation. J Cell Biol. 1999 Jan 11;144(1):161-73.
- Arikawa-Hirasawa E, Watanabe H, Takami H, Hassell JR, Yamada Y. Perlecan is essential for cartilage and cephalic development. Nat Genet. 1999 Nov;23(3): 354-8.
- "Peptides with laminin activity" by Y. Yamada, J. Graf, Y., Iwamoto, F. Robey, H.K. Kleinman, M. Sasaki, and G.R. Martin, U.S. Patent 5,092,885.
- ”Laminin A chain: deduced amino acid sequence, Expression vectors and active synthetic
- peptides" by Y. Yamada, H.K. Kleinman, M. Sasaki, and G.R. Martin, U.S. Patent 5,211,657.
- Teneurin-4-deficient mice as a tremor model, E-209-2009