The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases

 Naoki Nakayama, Ph.D.

Naoki Nakayama, Ph.D.

Associate Professor, Center for Stem Cell and Regenerative Medicine 

Naoki.Nakayama@uth.tmc.edu

Education & Training: Dr. Nakayama graduated from the University of Tokyo, Tokyo, Japan with a B.Sc majoring in Biophysics and Biochemistry.  In 1983 he received his M.Sc. from the University of Tokyo, Japan for his work on biochemical and genetic analysis of bacterial DNA replication proteins dnaB and dnaC.  With help of the late Dr. Arthur Kornberg at Stanford University Medical School, CA, he was able to pursue his Ph.D. at DNAX Research Institute, CA with his mentors Drs. Atsushi Miyajima and Ken-ichi Arai. He received Ph.D. from the University of Tokyo in 1987 for his work on molecular genetics of yeast peptide pheromone signal transduction, and continuously worked on the same project as a post doc at DNAX with Dr. Kunihiro Matsumoto, now in Nagoya University.

Professional Experience: Dr. Nakayama began his academic career as an Assistant Professor in the Department of Molecular and Developmental Biology, Institute of Medical Science, the University of Tokyo, Tokyo, Japan in 1990. There, he expanded his research interest to genetics of cytokine signaling, and initiated a program of construction and analysis of cytokine receptor b-chain knock-out mouse.  He also got interested in cellular basis of hematopoietic cell development using embryonic cell differentiation culture as a tool.  However, opportunity for stem and stromal cell EST analysis and a future path toward cellular therapy made him decide to move to biotech (Amgen, Inc., CA) in 1994, where he developed a method to direct mouse embryonic stem cells to generate blood cells and chondrocytes, and made many discoveries around adult marrow stroma and developing bone and cartilage.  In late 2003, Dr. Nakayama was recruited to Australian Stem Cell Center, Clayton VIC, Australia as a senior PI for directed differentiation of human and mouse pluripotent stem cells, where he focused on elucidating signaling network essential for specification of a particular type of mesoderm.  In late 2008, he joined the Brown Foundation Institute of Molecular Medicine, UTHSC at Houston.

Current Research Projects: Dr. Nakayama's research has been focusing on elucidating signaling events and cellular pathways that direct the differentiation of pluripotent stem cells to particular type of mesodermal progeny, and has an unbroken track record in this field. The lineages of interest are the building blocks of bone and bone marrow, such as chondrocytes, osteoblast/cytes and stromal cells, which overlap with the developmental potentials of adult mesenchymal stem cells. Besides the apparent benefit of such research for application to cellular therapy, Dr. Nakayama is also interested in utilizing the culture system to understand how stem cell loses its pluri/multipotency during differentiation.  Another long-standing interest is to elucidate the molecular and cellular basis of adult (i.e. mesenchymal) stem cell development during embryogenesis and in the adult.  Similar to Dr. Simmons' laboratory, Dr. Nakayama's laboratory also extensively uses flow cytometry, microarray-based transcriptional profiling, and transplant assays as the means to characterize pluripotent stem cell-derived progeny in vivo.

 

Selected publications:

  • Nishinakamura, R., Nakayama, N., Hirabayashi, Y., Inoue, T., Aud, D., McNeil, T., Azuma, S., Yoshida, S., Toyoda, Y., Arai, K., Miyajima, A., and Murray, R. (1995) "Mice deficient for the IL- 3/GM-CSF/IL-5 βc receptor exhibit lung pathology and impaired immune response, while βIL3 receptor-deficient mice are normal" Immunity 2, 211-222.
  • Nakayama, N., Fang, I., and Elliott, G. (1998) "Natural killer and B lymphoid potential in CD34+ cells derived from embryonic stem cells differentiated in the presence of vascular endothelial growth factor" Blood 91, 2283-2295.
  • Nakayama, N., Lee, J., and Chiu, L. (2000) "Vascular endothelial growth factor synergistically enhances bone morphogenetic protein-4-dependent lymphohematopoietic cell generation from embryonic stem cells in vitro" Blood 95, 2275-2283.
  • Nakayama, N., Han, C.-Y.E., Scully, S., Nishinakamura, R., He, C., Zeni, L., Yamane, H., Chang, D., Yu, D., Yokota, T., and Wen, D. (2001) "A novel chordin-like inhibitor for bone morphogenetic proteins expressed preferentially in mesenchymal cell lineages" Dev. Biol. 232, 372-387.
  • Nakayama, N., Duryea, D., Manoukian, R., Chow, G., and Han, C.-Y.E. (2003) "Macroscopic cartilage formation with embryonic stem cell-derived mesodermal progenitor cells" J. Cell Sci. 116, 2015-2028.
  • Nakayama, N., Han, C.-Y., Cam, L., Lee, J.I., Pretorius, J., Fisher, S., Rosenfeld, R., Scully, S., Nishinakamura, R., Duryea, D., Van, G., Bolon, B., Yokota, Y., and Zhang, K. (2004) "A novel chordin-like BMP inhibitor, CHL2, expressed preferentially in chondrocytes of developing cartilage and osteoarthritic cartilage" Development, 131, 229-240.
  • Tanaka M, Jokubaitis V, Wood C, Wang Y, Brouard N, Pera M, Hearn, M., Simmons, P., and Nakayama, N. (2009) "BMP inhibition stimulates WNT-dependent generation of chondrogenic mesoderm from embryonic stem cells" Stem Cell Res., 3, 126-141.
  • Wang Y. and Nakayama N. (2009) "WNT and BMP signaling are both required for hematopoietic cell development from human ES cells" Stem Cell Res., 3, 113-125.
  • Wang Y, Umeda K, and Nakayama N. (2010) “Collaboration between WNT and BMP signaling promotes hemoangiogenic cell development from human fibroblast-derived iPS cells”. Stem Cell Res. 4, 223-231.
  • Umeda, K., Zhao, J., Simmons, P., Stanley, E., Elefanty, A., and Nakayama, N. (2012) “Human chondrogenic paraxial mesoderm, directed specification and prospective isolation from pluripotent stem cells” Sci. Rep. 2,
  • Mae, S., Shono, A., Shioda, F., Yasuno, T., Kajiwara, M., Gotoda-Nishimura, N., Arai, S., Sato-Otsubo, A., Toyoda, T., Takahashi, K., Nakayama, N., Cowan, C.A., Aoi, T., Ogawa, S., McMahon, A.P., Yamanaka, S., Osafune, K. (2013) “Monitoring and robust induction of nephrogenic intermediate mesoderm from human pluripotent stem cells” Nat. Commun. 4, 1367.
  • Zhao, J., Li, S., Trilok, S., Tanaka, M., Jokubaitis-Jameson, V., Wang, B., Niwa, H., and Nakayama, N. (2014) “Small molecule-directed specification of sclerotome-like chondroprogenitors and induction of a somitic chondrogenesis program from embryonic stem cells” Development 141, 3848-3858.
  • Umeda, K., Oda, H., Yan, Q., Matthias, N., Zhao, J., Davis, B.R., and Nakayama, N. (2015) “Long-term expandable SOX9+ chondrogenic ectomesenchymal cells from human pluripotent stem cells” Stem Cell Reports 4, 712-26.
  • Yokoyama, K., Ikeya, M., Umeda, K., Oda, H., Nodomi, S., Nasu, A., Matsumoto, Y., Izawa, K., Horigome, K., Kusaka, T., Tanaka, T., Saito, M.K., Yasumi, T., Nishikomori, R., Ohara, O., Nakayama, N., Nakahata, T., Heike, T., and Toguchida, J. (2015) “Enhanced chondrogenesis of iPS cells from neonatal-onset multisystem inflammatory disease occurs via the caspase-1-independent cAMP/PKA/CREB pathway” Arthritis Rheumatol. 67, 302-314.