Center for Disease Biology andIntegrative Medicine

Molecular Biomedicine for Pathogenesis ———————————————————————————
http://www.cdbim.m.u-tokyo.ac.jp/english/index.html

Focusing on functional analysis of newly isolated genes, particularly related to apoptosis, cell differentiation, or cell cycle, our laboratory is pursuing clarification of the pathogenesis of various diseases and the related physiological machineries in cellular and molecular aspects. Based on ourtechnical advantage in gene manipulation via gene knockout and transgenesis, we give high priorities to in vivo analyses. Our overall goal is to apply our findings to development of novel and definitive therapies fortypes of diseases.

• Role of AIM (Apoptosis Inhibitor of Macrophage) in atherosclerosis

development and other diseases• Regulation of hematopoiesis and its relevance to leukemogenesis; via
functional analysis of a newly identified Polycomb group molecule
MBT-1• Regulation of tumorgenesis by modulating apoptosis and cell cycle;
via analysis of DEDD-deficient animals

Structual Physiology

http://www.bm2.m.u-tokyo.ac.jp/index-e.html

We have been exploring two-photon excitation microscopy,
which utilizes an infrared femtosecond-pulsed laser as alight source, to visualize and stimulate intact tissues at thecellular and molecular levels. We focus on the functions
and disorders of the brain and secretory organs.

• The dynamics of synapses in the cerebral cortex, in relation to memory, cognitive processes and mental disorders• Molecular mechanisms of exocytosis in synapses and the islet of
Langerhans, and their optical control

Fine structure and function of a central neuron studied with two-photon excitation imaging anduncaging

56

Regenerative Medical Engineering ———————————————————————————————
http://www.cdbim.m.u-tokyo.ac.jp/

We aim to create a basic methodology for tissue engineering by integrating engineering sciences such as mechanical, material, and chemical system engineering into basic and clinical medicine. Especially forthe regeneration of bones, cartilages, and blood vessels, we focus on
cellular response to physical stimulations, which can be utilized
instead of growth factors and cytokines. Besides, we focus on peritoneum as a place for in vivo tissue regeneration. Development of newbiomaterials such as porous materials, hydrogels, molecular signalresponsive materials is also one of our major missions.

• Development of new polymeric and inorganic biomaterials for regenerative

Ushida Lab

Ito Labmedicine• In vitro regeneration of carriages, bones, and small blood vessels• Mechanism of cellular response to physical stimulations• Development of new polymeric biomaterials for peritoneal diseases• Mathematical system design for tissue regeneration process• Development of molecular signal-responsive materials for a medical use

Clinical Biotechnology —————————————————————————————————————————
http://www.bmw.t.u-tokyo.ac.jp/english/index.html http://park.itc.u-tokyo.ac.jp/NBEP/index-en.html http://square.umin.ac.jp/t-e/Nanodevices produced by nanotechnology integrate materials and systems on a nanometer scale,and hold the key to realizing the futuristic medical system that can serve the needed function at
the right time and the right place with minimal invasiveness. Furthermore, nanodevices are expected to become an important interface between basic biomedical science and clinical medicine byfacilitating the translation of basic achievements into clinical applications. Our division wishes to produce revolutionary medical nanodevices based on nanotechnology and thereby to spread the idea of“Nanomedicine” intranationally and internationally.

• Development of nano-scaled carriers of drugs and genes based on polymeric micelles• Functional diagnostic imaging• Pinpoint cancer therapy• Gene therapy• Development of functional polymeric micelles responsive to external stimuli• Development of functional cell arrays based on nano-fabrication of polymers• Development of intelligent scaffolds delivering drugs and genes and their application to regenerative medicine

Environmental Health Sciences ———————————————————————————————————
http://env-health.m.u-tokyo.ac.jp/english/index.html

Children’s health problems of today include such conditions as disorders in the reproductive andimmune functions, learning deficits, mental problem and ‘metabolic syndrome’. Our research is carried out on the recognition that the homeostasis is disrupted by various environmentally hazardous
chemicals, to which expectant mothers and their newborn babies are exposed during their highly
sensitive period of life, and that the contamination with these chemicals may lead to various disease conditions in children after birth. Our experimental
investigations are focused on the following themes.

• Elucidation of mechanisms involved in the manifestation of toxicity

at the molecular and cellular level due to exposure to environmental
pollutants, such as dioxin/PCBs and heavy metals.
• Clarification of epigenetic mechanisms that alter susceptibility toenvironmental chemicals.
• Development of methodologies for evaluating the toxicity of chemicals to the learning and emotion of rodents and of in vitro toxicity
techniques at the molecular and cellular levels.
• Development and application of techniques and methodology forevaluating risks of toxic substances in formulating safety standard
for the environment and food.

57

Animal Resources / Research Resources and Support - Animal Research ————
Our laboratory focuses on understanding the molecular mechanisms which underlie the synaptic
plasticity, activity dependent formation of neuronal circuitry, and learning and memory. We generate knockout mice and inducible knockout mice of signal transduction molecules including the glutamate receptors. We also manage the animal facilities, give researchers advice on their animalexperiments, and give lectures on laboratory animal science so that animal experiments are carriedout in consideration of animal welfare.

• Molecular analysis of brain function using genetically modified mice
• Development of new reproductive technologies in mammals• Development of model animals for signal transduction diseases

A mutant mouse lacking metabotropic glutamate receptor subtype-1 (mGluR1).

Molecular Radiology / Research Resources and Support - Radiation Biology ——http://www.cdbim.m.u-tokyo.ac.jp/english/index.html

We are investigating the molecular mechanisms of DNA double-strand break repair as the scientificbasis of radiation therapy and chemotherapy in medical oncology. We also promote the basic
research that contributes to the development of a novel
therapeutic strategy by examining a link of the DNA
metabolic network including DNA replication and cell
cycle control with chromosome instability.

• Molecular mechanisms of homologous recombinational repair• Mechanisms of the choice between homologous recombination andnon-homologous end-joining• Molecular mechanisms of DNA rereplication• Mechanisms of the genesis of aneuploidy• Functional analysis of meiotic recombination genes

Centrosome fragmentation which may lead to aneuploidy

Research Resources and Support - Bioinformatics —————————————————————
http://www.cdbim.m.u-tokyo.ac.jp/english/index.html

Targeting biomedical research support using information
technologies, the division performs management of theresearch network and the central servers of the Graduate
School of Medicine, and researches on knowledge infrastructure and processing techniques (e.g. information
model, ontology, natural language processing, machinereasoning, etc.) and their application to clinical practice.

• Biomedical research support using network system• Medical terminologies and ontologies• Standardization of healthcare information and information models• Natural language processing and its application to the medicaldomain• Machine reasoning and clinical decision support systems

Computer System for Biomedical Research58