Research/The University of Tokyo

Laboratory of Organic and Medicinal Chemistry

https://yakka.f.u-tokyo.ac.jp/english/index.html
Prof. T. : Ohwada
Assoc. Prof. : Y. Otani

Synthesis of novel intelligent molecules bearing peculiar chemical structures and chemical and biological features on the basis of new concepts of organic and medicinal chemistry

Research Topics

1. Synthesis of new compounds exhibiting characteristic structural features and properties
2. New reactions to functionalize aromatic compounds based on designed superelectrophiles
3. Design and synthesis of intelligent molecules, which will have impacts on functions of membrane proteins
4. Theoretical calculation studies of organic reactions and structural features

Our aims of researches emphasize on design and synthesis of structurally novel organic molecules, which are characteristic in terms of structural (bonding) features and intrinsic functions such as chemical reactivities and biological functions. Designs of such novel molecules are based on our finding new chemistry including ground-state stable non-planar amide peptides and nitrosamines, and structures of multiply positively charged molecules. We study nitrogen-pyramidal amides and related nitrosamines, i.e., molecules that take nonplanar structures, different from the common planar amides. We apply this chemistry to construction of molecules of highly ordered structures such as helix peptide mimetics stable in water. We also develop new chemistry involving dication or trication molecules and apply them as superelectrophiles to synthesize a variety of novel multi-functionalized aromatic compounds, which are pharmaceutically relevant. We are also creating chemical molecules, which will be useful to controlling biological events of membrane proteins such as ion channels, neurotransporters and G-protein-coupled receptors. These molecules also contribute to understanding the phyisiological functions of these membrane proteins. We combine all the experimental projects with computational chemistry, which will lead to deep understanding of the underling chemistry.

Helical structure of artificial amino acid peptide stable in water

Chemical modulation of functions of membrane proteins

Laboratory of Synthetic Natural Products Chemistry

https://inoue.f.u-tokyo.ac.jp
Prof. : M. Inoue※
Assoc. Prof. : H. Itoh
Assist. Prof. : K. Hagiwara
Project Assist. Prof. : H. Fujino

Total synthesis and functional analysis of biologically active natural products

Research Topics

1. Development of new synthetic methodologies for total synthesis
2. Total synthesis of highly oxygenated polycyclic natural products
3. Total synthesis and functional analysis of ion channel-forming molecules
4. Total synthesis and functional analysis of antimicrobial molecules
5. Synthesis of new artificial molecules by modification of natural products templates

Natural products have been tremendously important in biology and human medicine because of their power to modulate signal transductions of biological system. Since the removal of sub-structures of the natural products often leads to significant losses of their activity, total chemical syntheses of their entire structures with a precision at an atomic level are necessary to provide sufficient amounts of material required for biological and medical applications. Architecturally complex natural products with molecular weight over 1000 are capable of highly specific interactions with their target proteins. Therefore, they are powerful agents for selectively controlling intricate biological systems. The goal of our research program is efficient, practical and flexible syntheses of gigantic natural molecules, which include highly oxygenated polycyclic natural products as well as ion channel-forming peptides. At the core of this research program is the development of new strategies for assembling architecturally complex natural products in a concise fashion. These synthetic developments would enable unified synthesis of new artificial analogs by modification of natural products templates. The new synthetic methods for the natural products and the synthetic analogs will allow us to tailor and enhance their drug like properties, to gain control over diverse signal transductions thereby offering new research methods for the study of life science.

Total synthesis of highly oxygenated polycyclic natural products

Total synthesis and functional analysis of biologically active peptides

Laboratory of Synthetic Organic Chemistry

https://gousei.f.u-tokyo.ac.jp
Prof. : M. Kanai
Assoc. Prof. : S. Kawashima
Assist. Prof. : H.Mitsunuma
Assist. Prof. : Y.Yamanashi

Catalysis for clean, robust, and concise complex molecule synthesis

Research Topics

1. Development of new catalysis to facilitate complex molecule synthesis
2. Clean, robust, and concise synthesis of pharmaceuticals and their leads
3. Catalytic H₂ and O₂ activation
4. Conceptually new approach to promote human health

The main theme of our research is the development of revolutionary catalyses facilitating new drug design and synthesis. In this direction, we would like to promote human health based on the catalysis development. Chemical synthesis in 21st century should be clean, robust, and concise, no matter how complex the target molecules are. The "ideal synthesis" will be only possible by new catalytic methodologies. Moreover, new catalyses will expand the diversity of readily available building blocks, leading to structurally novel artificial drug design. Sustainability based on new catalysis is another direction of our research. Specifically, we are interested in catalytic activations of small molecules such as H₂ and O₂.

New Catalysis and Drug Lead Discovery/Optimization

Respiratory C-C Bond-Forming Catalysis

Iterative Polyol Synthesis

Laboratory of Natural Products Chemistry

https://tennen.f.u-tokyo.ac.jp/head.htm
Prof. : I. Abe
Assoc. Prof. : T. Mori
Assist. Prof. : R Ushimaru

We establish the mechanisms of natural product biosynthesis as a science in their own right, to construct a rational system for the production of new and useful substances

Research Topics

1. The biosynthesis and bioengineering of medicinal natural products
   (genome mining, engineered biosynthesis)
2. The enzyme biocatalysts (structure-function analysis, enzyme engineering, mechanistic studies)
3. The search for bioactive substances and isolation/structure determination

Natural organic compounds, prominent among which are antibiotics such as penicillin, are gifts from nature, and the benefits they have bestowed upon humankind as sources for the pharmaceuticals, etc., that maintain health is inestimable. In our laboratory, we study the process of biosynthesis of natural organic compounds produced by plants and microorganisms, using not only the foundation discipline of organic chemistry, but also incorporating the methods of biochemistry and molecular biology in an effort to understand the enzymes that catalyze each biosynthesis reaction and the functions and control mechanisms of the genes that govern their expression at the molecular level. In addition, we are expanding our research into "biosynthesis engineering," by which rational systems for the biological production of new and useful substances can be designed and constructed, based on the mechanisms of biosynthesis that have been brought to light. We also are carrying out research on the mechanisms by which the bioactivity of natural products is expressed, while at the same time searching for natural products that are active in intracellular signaling.

Concept of biosynthesis engineering, by which non-natural compounds are generated

Plant polyketide based on crystalline structure function control of synthetic enzymes and the production of substances

Laboratory of Advanced Elements Chemistry

https://kisoyuki.f.u-tokyo.ac.jp
Prof. : M. Uchiyama
Assoc. Prof. : K. Miyamoto
Project Assoc. Prof. : M. Nakajima
Assist. Prof. : N. Toriumi

Understanding of chemical phenomena at the atomic and electron levels and creation of a new science of materials through flexible construction of molecules

Research Topics

1. Development of advanced molecular transformation methods supporting materials science and life sciences (methodology development/synthetic chemistry)
2. Periodic table-traversing chemistry that transcends the frameworks of organic chemistry, inorganic chemistry, and metallic chemistry (elements chemistry)
3. Elucidation of the structural chemistry of intermediates and transitional states (physical chemistry, spectroscopy, theoretical calculation)
4. Design and production of materials founded on synthetic chemistry, spectroscopy, and computational chemistry (materials science/life sciences)

Our laboratory focuses on understanding the properties and phenomena of substances by "language of chemistry" such as molecules, atoms, and electrons (Seeing /Knowing); on developing reactions that manipulate the bonds between atoms completely in control (Designing); and on producing functional materials (Producing).
In our laboratory, we strive to develop technologies for the precise chemical conversion of tiny, tiny molecules less than 1 billionth of a meter in size (nanometer scale; nm). Thanks to recent advances in spectroscopy and theoretical calculation, it is getting possible to accurately predict and reproduce snapshots of the state of the electrons that form materials, as well as of reactions between molecules. With the 3 methods, namely, synthetic chemistry, spectroscopy, and theoretical calculation as the pillars of our science, we expand upon elements chemistry in an interdisciplinary manner as we meet the challenges of elucidating life phenomena and creating a new materials science.

Developing new reactions and designing/producing new materials based on computational chemistry and theoretical chemistry (Adopted for the cover of Chemistry: A European Journal)

Life sciences and materials science that open new frontiers in basic organic chemistry and elemental chemistry

Laboratory of Medicinal Plant Chemistry (Experimental Station for Medicinal Plant Studies)

https://www.f.u-tokyo.ac.jp/~oriharay/index.htm

An overall analysis is made of the old-yet-new drugs known as "medicinal plants" (crude drugs) to develop new ways of using them (utilizing the resources in the Experimental Station for Medicinal Plant Studies)

Research Topics

1. The cultivation of medicinal plants and tissue cultures
2. The production of useful secondary metabolites, using plant tissue culture technology
3. Chemistry and biosynthesis of plant-derived biologically active substances

Since prehistoric times, plants have been the principal material used as drugs by humankind. Many have fallen by the wayside through a long process of trial and error (human experiments), and the ones that remain can be considered the crude drugs of the present day. In recent years, the percentage of all drugs accounted for by antibiotics and biologics has increased, but the importance of plant-derived pharmaceuticals is by no means diminished and has led to the discovery of new drugs such as Taxol and vinblastine. Thus, the study of medicinal plants is by no means completed, and is continuing to evolve.
The Experimental Station for Medicinal Plant Studies, formally established in 1973, is located adjacent to the Kemigawa Athletic Ground. The saplings transplanted there back then have grown large and now form a dense enclosure of trees around the garden.
At the research lab in Hongo, we conduct research on the production of useful secondary metabolites using plant tissue culture technologies (from the induction of culture cells to the production of substances). Some of the research topics we are currently pursuing are the biosynthesis of diterpene constituents from Gymnosperm plant cultured cells, the production and biosynthesis of diterpene alkaloids using cultured tissue of monkshood, the production and biosynthesis of phenylethanoids using cultured cells of olive, and the production of biologically active constituents of Egyptian medicinal plants by means of plant tissue culture technologies.

Aconitum japonicum cultured root

The sweetener glycyrrhizin is contained in the roots and stolons of Glycyrrhiza uralensis Fisher

Laboratory of Bioanalytical Chemistry

https://bunseki.f.u-tokyo.ac.jp/index_e.html
Prof. : T. Funatsu
Visiting Prof. : H. Kimura
Assoc. Prof. : M. Tsunoda
Assist. Prof. : K. Okabe

We measure the functions of biomolecules at the level of a single molecule to elucidate vital functions

Research Topics

1. Research on the principles of action by which biomolecular machines such as molecular chaperonin and ribosomes operate
2. Single-molecule fluorescence imaging of intracellular mRNA processing and transport
3. Development of micro nanodevices for analyzing the functions and interactions of biomolecules

In order to understand living organisms, it is necessary to conduct research at a variety of different levels. The lowest level is that at which biomolecules such as proteins and DNA work. When these come together, biological supramolecules, cells, organs, and the like are created, while at the higher end, individual organisms, societies, and ecosystems are constituted. We focus on the level of the smallest unit, the "biomolecule," together with the level of the "cell," at which life functions are first expressed, to find answers to questions like "By what mechanisms do biomolecules function?" and "When they aggregate, what kinds of systems do they construct?"　Concretely speaking, we bind a fluorescent dye to a single biomolecule and observe it with a sensitive fluorescence microscope. Some biomolecules can exhibit their functions even at the level of the single molecule. For example, the motor protein known as kinesin moves on rail proteins called microtubules. Humankind does not at this point in time possess the technology for creating this kind of molecular machine, but we believe that humankind will be able to make this kind of molecular machine in the near future through research on the motor protein. On the other hand, self-assembly of a variety of different biomolecules creates complex systems which differ greatly from manmade ones. By researching such biological systems, we close in on the mysteries of life.

Fluorescence microscope system for imaging single molecules within living cells

The principle of single-molecule imaging of enzyme reaction (ATPase) using evanescent illumination

Laboratory of Physical Chemistry

https://biophys.f.u-tokyo.ac.jp/en
Prof. : K. Takeuchi
Assoc. Prof. : T. Ueda
Assist. Prof. : Y. Kofuku
Assist. Prof. : Y. Tokunaga

Approaching life from dynamic structural information obtained by original NMR strategies.

Research Topics
    1. Functional mechanism of biologically and pharmacologically important proteins based on dynamic structural information.
    2. Functional mechanism of biomolecules that regulate signal transduction and energy metabolism based on interaction analysis.
    3. Development of NMR techniques to analyze the structure and dynamics of high-molecular-weight proteins.
    4. Strategies to reproduce the functional environment of biomolecules and sophisticated stable isotope labeling methods.
    5. In-cell NMR and its application to intracellular drug discovery.


　The structural information of proteins plays a vital role in elucidating biological functions and their applications to drug discovery. In addition, it has become clear that proteins do not adopt only a single conformation but also an equilibrium among multiple functional conformations. These dynamic properties are directly related to the expression and regulation of protein functions.
　In our lab, we analyze the structure and dynamics of proteins mainly by using NMR to understand biological phenomena through elucidating the functional mechanisms of biomolecules. We focus on membrane proteins, such as G-protein-coupled receptors (GPCRs) and transporters, as well as macro-molecules that regulate intra-cellular signal transduction and energy metabolism, which are important in biological and pharmaceutical sciences. By developing original NMR methods, we have obtained structure and dynamics information of the macromolecules of interest that were previously difficult to analyze. In addition, we are developing an in-cell NMR strategy to analyze the structure and dynamics of proteins in the actual cellular environment and extending these strategies to establish intracellular drug discovery.
 

Fig. 1 Biological phenomena elucidated by dynamic structural analysis using NMR in our laboratory. (A) Structural equilibrium determines (B) transcriptional activity of multidrug-resistant transcription factors (Proc Natl Acad Sci (2019) 116, 19963. (C) Drug efficacy of each ligand of GPCR (β2 adrenergic receptor) (NatCommun (2012) 3, 1045: Angew Chem Intl Ed (2014), 53, 13376).

Fig. 2 Novel NMR experiments developed in our laboratory and their application to mAb (J Med Chem. (2020) 63, 5360: Nat Methods. (2019) 16, 333).

Laboratory of Health Chemistry

https://sites.google.com/view/eiseikagaku-en/
Prof. : J. Aoki
Assoc. Prof. : N. Kono
Assist. Prof.：K.Kano

Exploration of new functions for biomembranes and their constituent lipids

Research Topics

1. Molecular mechanism of lipid biosynthesis and homeostasis
2. Molecular mechanism of membrane dynamics (e.g., endo/exocytosis)
3. Elucidation of functions of lipid mediators in inflammatory diseases
4. Identification of new bioactive lipids and elucidation of their functions

Biomembranes serve as barriers that segregate cells from the external environment. They also produce intracellular organelles, and are essential for cellular functions. The Laboratory of Health Chemisty aims to elucidate the physiological functions of lipids, essential constituents of biomembranes. Over 1,000 lipid species exist in biomembranes, and the appropriate balance among them is assumed to be fundamental to stability, activity, and localization of proteins, and regulation of gene expression. We focus on major components of cellular lipids, called phospholipids, and are trying to identify proteins involved in their biosynthesis and homeostasis. We also study the functions of lipids in the dynamic behavior of biomembranes, such as endo/exocytosis.
Various bioactive lipids are formed from membrane phospholipids, and affect a range of biological phenomena and diseases. Our study also focuses on "inflammatory response" which is the underlying condition of lifestyle-related diseases. To better understand the molecular mechanisms underlying inflammation, we are trying to comprehensively clarify when, where and how much lipid mediators are formed in the inflammatory sites using LC-ESI-MS/MS-based lipidomics system.

The functions of membrane lipids

Lipid-related diseases

Laboratory of Physiological Chemistry

https://seirikagaku.f.u-tokyo.ac.jp
Prof. D. : Kitagawa
Lecturer : M. Fukuyama
Project Lecturer : S. Hata
Assist. Prof. : T. Chinen

Mechanisms of cell division and their application to drug development

Research Topics

1. Mechanisms of centrosome duplication and its theoretical model
2. Mechanisms of cell division regulated by divergent molecular machineries
3. Identification and characterization of non-coding RNAs that regulate cell division
4. Comparative cancer cell biology and its application to anticancer drug development
5. Forward genetic analysis of cell-cell communication with human cells

Our laboratory mainly focuses on understanding the mechanisms of cell division, with aparticular emphasis on the molecular basis and theoretical model of centrosome duplication. We are also interested in elucidating how divergent molecular machineries, including a protein complex and protein-lncRNA complex, regulate somatic and meiotic cell division. Based on these studies,we then explore a new approach to develop anovel anti-cancer therapy.To this end, we currently use the combination of innovative and multi-disciplinary methods including molecular biology, biochemistry, biophysics, structuralbiology, genetics, computer simulation and cellbiology.
Furthermore, to understand molecular mechanisms and basic principles underlying a wider range of biological phenomena in vivo, we are also trying to establish a forward genetic approach with in vitro reconstitution of human cell-cell communication.
 

Bipolar spindle formation in mitotic HeLa cells. Control (left panel) and a cell defective in forming a proper mitotic spindle and chromosome segregation (right panel).

Centriole duplication and structure. An image obtained by super-resolution microscopy: centriole wall in green, cartwheel structures in red.

Laboratory of Molecular Biology

https://molbio.f.u-tokyo.ac.jp
Prof. : Y. Gotoh
Assoc. Prof. : D. Kawaguchi
Project Assoc. Prof. : K. Oishi
Assist. Prof. : T. Kuniya
Project Assist. Prof. :F.LINGYAN

Our long-term goal is to provide new vistas in immunity and pathogenesis on the basis of glycosciences and to develop new diagnostic and therapeutic tools for currently incurable diseases. The main focuses are on immunology, oncology, and infectious diseases.

Research Topics

1. Biological function and medical application of mucins, such as MUC21
2. Immunological significance of C-type lectins, such as MGL/CD301, expressed on dendritic cells and macrophages
3. Biological roles of glycosidases, such as heparanase, in immunity and cancer
4. Molecular mechanism of cancer metastases and methods to eradicate micrometastases

To understand the mechanism of disease processes, we focus on cellular interactions. Carbohydrate chains found on cell surfaces and in the extracellular matrix, abundant and extremely variable in modifications, are believed to cause significant impact in these interactions. These carbohydrate chains play vital roles in disease process through specialized molecules such as mucins (heavily glycosylated glycoproteins), lectins (carbohydrate recognition molecules), and glycosidases (degradation enzymes for carbohydrate chains). We discovered a novel mucin (MUC21), lectin (MGL/CD301), and glycosidase (heparanase), and have proved that these molecules were the essential elements in several disease processes including viral infection, hypersensitivity inflammatory diseases, and cancer metastases. By applying modern scientific technologies such as the developments of gene deficient mice, specific monoclonal antibodies, in vitro assays, and analytical techniques, the significant roles of these complex molecules were further established. It is our mission to develop diagnostic tools, therapeutic modalities, and preventive measures, through elucidation the mechanisms of these molecules as they play the pivotal role in the disease processes.

Laboratory of Genetics

https://idenut.f.u-tokyo.ac.jp
Prof. : M. Miura
Lecturer : Y. Nakajima
Assist. Prof. : S. Kashio
Assist. Prof. : N Shinoda
Assist. Prof. : S. Uchiyama

Research of development, growth, aging, and behavior from the perspective of cell society

Research Topics

1. Regulation and function of cell death signaling in development, growth, and aging
2. Regulation of cell number and size of tissue via programmed cell death
3. Formation and maintenance of neural network
4. Metabolic regulation of development and growth
5. Molecular mechanisms of hibernation
6. Neural mechanisms of social behavior

Programmed cell death functions in dynamic tissue formation or remodeling. We have revealed that in the embryonic development, or aging process, caspases are activated by various physiological stresses and exert regulatory functions. We aim to reveal how cell society is constructed and maintained during development, growth, and aging process with a particular focus on understanding the regulatory mechanisms and functions of cell death. From the perspective of cell sociology, we are also studying the unique biological phenomena such as neural development, hibernation and behavior by using various model animals. We believe that our research would stimulate and encourage students and researchers to have the breadth of vision for life science research and provide new insights into the molecular logic underlying the formation and maintenance of cell society.

Fig. 1: Caspases are activated in cells exposed to various environmental stresses (Left). To monitor the activation state of caspase in live cells, we generated a genetically encoded sensor for caspase activation based on FRET, named SCAT3 (Right). Color change from red to blue reflects the activation state of caspase (Left bottom). Fig. 2: Birth and selection by cell death of neural precursor cells during the development of Drosophila sensory organ Fig. 3: Live-imaging of apoptosis in the neural tube closure of mouse brain Fig. 4: Genetic labeling and manipulation of olfactory projection neurons in Drosophila brain

Laboratory of Cell Signaling

https://saijyou.f.u-tokyo.ac.jp/en/index.html
Prof. : H. Ichijo
Assoc. Prof. : I. Naguro
Assist. Prof. : T. Fujisawa
Assist. Prof. : S. Yamauchi

From signal transduction to drug discovery

Research Topics

1. Signal transduction and functions of ASK family proteins
2. Exploration of novel signaling molecules involved in cell death and stress responses
3. Molecular mechanisms of pathogenesis induced by dysfunction of stress signaling

The Laboratory of Cell Signaling has been focusing on analyses of the intracellular signal transduction, through which we seek to elucidate molecular basis of human diseases and identify novel drug targets. Our current research mainly focuses on the pathophysiological roles of stress responsive signals in various diseases such as cancers, immune disorders, cardiovascular diseases and neurodegenerative diseases. In addition to molecular genetic tools such as mice, flies and worms as well as basic experimental techniques from molecular cloning to protein biochemistry, we always incorporate novel analytic technologies such as mass spectrometry-based proteomic analysis and genome-wide RNAi screening systems into our research exploring"target molecules and molecular mechanisms". By taking advantage of such experimental approaches, we aim to open up new fields in pharmaceutical sciences with paying attention to whole body physiology, diseases and drug discovery.

MAP kinase pathways in mammals

Analysis of stress signaling at levels of molecules, cells and bodies

Laboratory of Protein Metabolism

https://tanpaku.f.u-tokyo.ac.jp/
Prof. : S. Murata
Lecturer. : J. Hamazaki
Assist. Prof. : S. Hirayama

Elucidating various biological phenomena controlled by proteolysis

Research Topics

1. The action mechanisms of the proteasome, a multisubunit macromolecular complex responsible for regulated protein degradation in eukaryotic cells
2. Proteasome dysfunction in human diseases (senescence, malignant tumors, inflammation, neurodegeneration)
3. The mechanism of maintenance of protein homeostasis by the ubiquitin-proteasome system
4. The mechanism of T-cell positive selection by the thymus-specific proteasome

The proteasome is a supramolecular proteolytic apparatus that exists in all eukaryotic cells. The proteasome plays pivotal roles in various cellular functions by selectively degrading ubiquitinated proteins. It is also central to the maintenance of protein homeostasis (proteostasis). In recent years, it has become evident that the impairment of proteostasis is a hallmark of senescence, and the decline of proteasome function is drawing attention as one of the primary factors. Indeed, it has been shown that age-associated diseases develop as proteasome function declines with age, and that artificial increase in proteasome activity prolongs the healthy lifespan in nematodes and Drosophila. However, in mammals, means to enhance proteasome function has not been found at present. This is because in mammals the proteasome is controlled more complicatedly and because the mechanisms by which the proteasome function decreases with aging and by which a decrease in proteasome function causes senescence are not understood. On the other hand, it has become clear that inhibition of proteasome function is an important therapeutic strategy in malignant tumors where proteasome hyperactivity is observed.
The ultimate goal of Laboratory of Protein Metabolism is to create a method of intervention in pathologies involving proteasome dysfunction. To this end, we are researching detailed mechanisms of action and regulation of the proteasome by using techniques such as molecular and cell biology, comprehensive gene screening, proteomics, and mouse genetics.

Laboratory of Pathology and Development(Institute for Quantitative Biosciences )

Prof. : Y. Okada

Laboratory of Cellular and molecular chemistry (Institute of Medical Science, Division of Cellular and Molecular Biology)

Prof. : A. Iwama
Assist. Prof. : M. Oshima
Assist. Prof. : N. Nakajima

Laboratory of Molecular Neurobiology(Institute for Quantitative Biosciences )

https://www.kishilab.iqb.u-tokyo.ac.jp/en
Assoc. Prof. : Y.Kishi
Assist. Prof. : M.Bilgic

Understanding how the brain functions through epigenetic analysis

Research Topics
      1. Epigenetics analysis of brain cells to understand alterations in brain function under aging, stress, and psychiatric disorder conditions
      2. Epigenome editing of neurons to improve brain function   


Our genetic information is encoded in our genomic DNA. Several mechanisms are used to properly identify and access the necessary genetic information contained within our three billion base pairs of DNA. One of these mechanisms is epigenetic regulation. Through epigenetic regulation, chemical modifications on DNA and histones—such as methylation and acetylation—function as “bookmarks,” resulting in the expression of only the necessary genes.

These epigenetic “bookmarks” are modified in response to the cell’s previous exposures to stimuli and experiences. In other words, epigenetic regulation functions as the memory system of cells. The question then becomes, what role does epigenetics play in the brain, which is the memory system of individuals?

In our laboratory, we are working to understand the mysteries of the brain through epigenetic analysis by combining the biochemical, molecular biological, and bioinformatics technologies needed to carry out the latest genomic analysis with the genetic and neuroscience technologies necessary to analyze brain function. Through this research, we aim to understand the basis of changes in brain function caused by aging, stress, and psychiatric disorders.


 

Social Cooperation Program of Targeted Protein Degradation

https://tpd.f.u-tokyo.ac.jp/en/index.html
Professor : S. Murata
Project Prof. : M.Naito
 

Inducing targeted protein degradation by chemical compounds

Research Topics

1. Development of new technologies to induce protein degradation
2. Development of SNIPER compounds that degrade disease causative proteins

When the mechanisms of various diseases are deeply understood at the molecular level, we can develop molecularly targeted drugs that specifically inhibit disease causative proteins. However, it is not possible to develop molecularly targeted drugs against all proteins. In particular, many intracellular proteins without enzymatic activity have been considered to be undruggable. Protein knockdown technology,which specifically degrades target proteins, is a promising technology to develop novel drugs against undruggable targets. Chimeric compounds such as PROTACs and SNIPERs are attracting attention because they enable the rational development of compounds that degrade proteins of your interest.
In our laboratory, we have developed a series of SNIPER compounds that degrade various target proteins. SNIPERs recruit IAP ubiquitin ligases to target proteins for ubiquitylation and proteasomal degradation. We are currently developing new technologies to induce protein degradation, which include cancer-specific or tissue-specific degradation of target proteins. We are also developing new compounds that degrade disease causative proteins.