Sumiko Watanabe Lab

Former Prof. Arai, who founded our laboratory was also involved in establishing the DNAX Institute in the suburbs of San Francisco, where he spent about 15 years cloning cytokines and cytokine receptors. After setting up our laboratory at IMSUT in 1989, he went on to make elucidation of cytokine receptor signaling and its role in blood cell differentiation and proliferation the central focus of research.
Currently, our research focuses on general stem cell mechanisms involved in the development and regeneration of higher level structures in a constituent of the central nervous system, the eye. This research is aimed at elucidating tissue stem cell-specific mechanisms, but the underpinnings of these studies have been the knowledge and techniques of signal transduction and DNA synthesis that the cytokine research nurtured, giving us the tools to unravel the processes by which organs develop and regenerate. .

Research project
Laboratory characteristics/features
1. We utilise mice, cell cultures, and animal models (mouse, monkey) of every description centered around induced pluripotent stem (iPS) cells, sharing our knowledge and using multi-pronged approaches to advance our research.
2. Clarify the special characteristics and common features of development and regeneration of blood and especially the retina.
3. Elucidate the mechanisms of development from a regulatory signaling perspective, and via a logical approach draw connections to tissue regeneration research.
4. Introduction of human studies targeting clinical application: through collaboration with other universities and hospital ophthalmology departments we have begun analyzing clinical samples and carrying out experiments with peripheral blood, constantly (probing/on the lookout) for clinical applications.

Below the individual projects:
1. Eye (retina) development and regeneration
For our research we rely mainly on engineered knockout and transgenic mouse lines, mouse retina culture, injection of RNA and morpholino antisense oligos into fertilised zebra fish eggs for rapid analyses, and iPS cells. Finally we would like to revive our lab's background in signal transduction to unravel mechanisms regulating eye development. And as the trends in tissue and organ regeneration have finally started to take form, we are looking into monkey retina animal models for pursuing clinical applications. In addition, we are expanding research into nuclear transcription factors that play important roles in retina development. 2. Screening for novel genes involved in early eye development
With tools such as microarrays we are using the mouse to try to isolate genes involved in early-stage retina development. In the instance of a genes isolated from mice, we quickly isolate zebrafish homologs, use zebrafish to analyze their function in eye development, and create knockout mice for genes that seem to possess functions of interest, and are currently focusing on carrying out functional analysis for several novel genes.
3. Screening for retina stem cells and determination of cell lineages
From an experimentalist's perspective the retina is an attractive system in which to explore stem cells in the central nervous system, but to date the existence and identities of retina stem cells remain unclear. Making full use of the knowledge and technologies for cell fractionation and lineage determination that have arisen from hematopoietic stem cell research and combining this with cell transplantation systems that arose from iPS cell research, we are trying to isolate retina stem cells.
More specifically, we are screening undifferentiated mouse retina for cell surface molecules (surface antigens) using a battery of antibodies, using the corresponding antibodies for retinal cell sorting to isolate specific subpopulations, and testing proliferative and differentiation potential to track down undifferentiated retina cell subpopulations and determine cell lineages.
4. Establishment of iPS from patients of inherited retinal degeneration diseases.
This project is in collaboration with Junten-do University, Ophthalmology department. We established several iPS lines from the patients, and used the iPS for in vitro differentiation to retina by 3D organ culture system to elucidate molecular mechanisms of retinal degeneration.
5. Functional analysis of candidate cancer genes that have been identified through transposon mutagenesis screens
The Sleeping Beauty (SB) transposon mutagenesis is an unbiased and high-throughput method to profile the landscape of driver genes in a mouse model system. Glioblastoma multiforme (GBM) is the most common form of malignant brain cancer in adults. Patients with GBM have a uniformly poor prognosis, with a mean survival of one year. Thus, advances on all fronts, both basic and applied, are needed in order to combat this deadly disease. To better understand genes and signaling pathways that are able to transform neural stem cells into glioma-initiating cells, we have performed a transposon mutagenesis screen in mice, and identified new genes responsible for progression of glioblastoma and meduloblastoma.


Current staff members are:
Sumiko Watanabe: Professor
Hideto Koso, MD, Ph.D: Research Associate

Members

Address: Shirokane-dai 4-6-1, Minatoku-ku, Tokyo 108-8639, Japana
Phone: 81-3-5449-5663 or 5664 FAX: 81-3-5449-5474
e mail: sumiko (atmark) ims.u-tokyo.ac.jp

last up-dated Nov 20, 2013

Publications