代謝ネットワーク解析クラスタ C l u s t e r f o r M e t a b o l o m i c N e t w o r k s27

　 I had succeeded in developing an original CE-MS metabolomics technology that enables the comprehensive and quantitative analysis of nearly all cationic and anionic metabolites in any cell or tissue. Using this approach, I looked to study multiple changes in metabolite levels between normal and tumor tissues obtained from stomach and colon cancer patients and gain insights into the cancer metabolism and

found specific cancer metabolism that might be a target for anti-cancer drug development. We also applied the CE-MS metabolome profiling methods to serum samples obtained from patients with nine different liver diseases and discovered new biomarkers that can discriminate among different forms of liver disease.

　CE-MS is a powerful new tool for metabolome analysis; it is applicable to a wide range of bio-medical fields, for screening metabolic abnormalit ies or diagnosing biomarkers in

physiological samples; it is also useful in discovery and drug efficacy and toxicity studies, in drug development.

　I developed comprehensive, quantitative and highly sensitive capillary electrophoresis time of fl ight mass spectrometry (CE-TOFMS) methods for charged metabolites, which enabled simultaneous analysis of thousands of charged metabolites. The efficiency of CE-TOFMS was demonstrated in biomedical fields. 　We profiled mouse liver and serum metabolites following acetaminophen-induced hepatotoxicity, globally detected 1,859 peaks in mouse liver extracts, and found the elevation of the level of ophthalmate in both liver and serum. We revealed that ophthalmate was synthesized with gamma-glutamylcysteine synthetase (GSC) and glutathione synthetase, like glutathione (GSH) and can be a new biomarker for liver disease. 　Subsequently, to evaluate this biomarker response, we

analyzed a total of 248 serum samples obtained from nine types of liver disease including liver cirrhosis, hepatocellular carcinoma and non-alcoholic steatohepatitis (NASH). We found that in liver diseases in humans, many gamma-glutamyl dipeptides, which were synthesized from many amino acids with GCS, were increased and could provide specific information for different liver diseases. Mult iple logist ic regression models faci l i tated the discrimination between specific and other liver diseases and yielded high areas under receiver-operating characteristic curves. The area under the curve values in training and independent validation data were 0.952 and 0.967 in healthy controls, 0.817 and 0.849 in drug-induced liver injury, 0.754 and 0.763 in asymptomatic hepatitis B virus infection, 0.820 and 0.762 in chronic hepatitis B, 0.972 and 0.895 in hepatitis C

SUMMARY OF RESEARCH

FUTURE GOALS

　My contribution in G-COE was to develop advanced CE-MS methodologies, including the development of highly sensitive and comprehensive metabolomic profiling methods, a metabolite database and an identification tool for unknown

compounds. The provision of CE-MS methods was able to help collaborators measure multiple changes in metabolite levels, to understand the metabolism of their interest.

MISSION

　My contribution to the G-COE program was metabolomics collaboration with many researchers in various life-science fields. In this program, I obtained a variety of scientific information from experts in various f ields, and I had

opportunities to collaborate with leading scientists from all over the world, allowing me to add to my personal body of knowledge.

APPEAL OF G-COE

Metabolomic Analysis based on Advanced CE-MS technology

01_事業推進担当者.indd 27 12/01/26 16:10

Global COE Program

PROFILE

代謝ネットワーク解析クラスタ　活動実績

Cluster for M

etabolom

ic Netw

orks

28

with persistently normal alanine transaminase, 0.917 and 0.707 in chronic hepatitis C, 0.803 and 0.993 in cirrhosis type C, and 0.762 and 0.803 in hepatocellular carcinoma, respectively. Several gamma-glutamyl dipeptides also manifested potential for differentiating between nonalcoholic steatohepatitis and simple steatosis. 　For study of cancer metabolism, we applied the CE-MS approach to simultaneously measure metabolite levels in tumor and normal tissues obtained from 16 colon and 12 stomach cancer patients. Quantification of 95 metabolites in colon and stomach resulted in the identifi cation of several cancer-specifi c metabolic traits. Extremely low glucose, high glycolytic intermediates, and high lactate concentrations were found in both tumor tissues, which indicated enhanced glycolysis, which confirms the Warburg effect. In addition, significant

organ-specific differences were found in the levels of TCA metabolites. The results uncovered the unexpectedly poor nutritional conditions of the actual tumor microenvironment and demonstrated the potential of CE-MS-based metabolomics, which is capable of quantifying the energy metabolism of tissues as a whole, which could be crucial for the development of novel anticancer agents that target cancer-specific metabolism. 　In this G-COE program, I collaborated with more than 20 graduated students, researchers and medical doctors in medical and life science area. In these collaborations, I was able to understand what they were currently interested in, or which types of disease required useful biomarkers. These information provided me the direction that I should go using metabolomics.

1984 年 慶應大工学部応用化学科卒業。横河電機㈱入社で分析装置の応用開発。1992 年 横河アナリティカルシステムズ㈱で分析装置の応用開発。2000 年 工学博士（論文博士）取得（豊橋技術科学大学）。2001 年 慶應大環境情報学部および先端生命科学研究所助教授2006 年～現在 慶應大環境情報学部および先端生命科学研究所教授2008 年～現在 慶應大医学部教授（兼担）

ProfessorFaculty of Environment and Information StudiesProfessorInstitute for Advanced Biosciences, Keio UniversityProfessorSchool of Medicine, Keio University

慶應義塾大学環境情報学部および慶應義塾大学先端生命科学研究所教授慶應義塾大学医学部教授

（兼担）

Tomoyoshi Soga曽我　朋義

01_事業推進担当者.indd 28 12/01/26 16:10

代謝ネットワーク解析クラスタ C l u s t e r f o r M e t a b o l o m i c N e t w o r k s29

　Tsuruoka Town campus of Keio (TTCK) consists of Institute for Advanced Biosciences of Keio University (Director: Masaru Tomita) and its spin-out company, Human Metabolome Technologies Inc. (Founder: Masaru Tomita). TTCK forms the world’s largest metabolomics research center, and the center possess twenty one (21) sets of ESI-TOFMS, five (5) Q-TOFMS, twelve (12) Q-MS, two (2) Ion-trap-MS, three (3) Orbitrap MS, three (3) Triple Q-MS/MS, one (1) MALDI-TOFMS, one (1) NMR, as well as thirty five (35) sets of CE, fourteen (18)

sets of LC and nano-LC, and two (2) sets of GC/MS. 　The center’s main force is capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS) developed by Keio [1]. The technology can simultaneously quantify a large number of cellular metabolites ranged from 70 to 1,000 molecular weights, and is being applied to various fields of biotechnology in the post-genomic era, such as medical diagnosis (blood, urine, saliva, tissue), food science, and systems biology of model organisms [2].

　We have recently discovered serum biomarkers of hepatotoxicity [3,4] and saliva biomarkers of oral, breast and pancreatic cancer [5]. Furthermore, metabolome data have been used to successfully confirm simulation results of red blood cell metabolism [6,7] and to discover cancer-specific energy metabolism [8].　In the area of food science, we conducted metabolome analysis of soybeans [9], and sake (rice wine) and its correlation with taste [10]. These activities are adding value

to local agricultural goods, through such discoveries as the flavorful balance of aspartic and glutamic acids found in "Tsuya-hime" rice.　When we announced the revolutionary technology of "diagnosing cancer through saliva" [5] in June 2010, it made headlines around the world. We are currently organizing a series of study sessions / workshops with the Yamagata Dental Association with a goal of achieving practical use of the technique within 10 year's time.

　A bio-venture company launched by Keio called Human Metabolome Technologies, Inc. (HMT), was founded on the "Metabolome Analysis" technique. This company has achieved significant results, and is set to become the sole public-listed company in all of Tsuruoka city, generating high expectations throughout the local community. 　Meanwhile, "Spiber, Inc.," a venture company founded by

Keio students in Tsuruoka City based on the artificial synthesis of eco-friendly "spider silk," was awarded top prize at the 9th Bio Business Competition Japan, while also being honored as the youngest group ever to receive the "Distinguished Contribution to Science and Technology" award in 2010, issued by the National Institute of Science and Technology.

　Last years, many doctorate students have been awarded a Ph.D under supervision of Masaru Tomita. Those young doctors have obtained faculty and post-doc positions at various universities and research institutes around the world, including NASA, Harvard Medical School, University of California San Diego, University of California San Francisco,

Cornell University, Molecular Science Institute, Cambridge University, Toronto University, Max Plank Institute, FOM Institute, Osaka University and Tokyo Institute Technology, as well as three (3) at Tokyo University and six (6) at Keio University.

Omics-data driven systems biology

Metabolomics Technologies

Practical Applications and Results

Spin-off Companies

Education

01_事業推進担当者.indd 29 12/01/26 16:10

Global COE Program

PROFILE

代謝ネットワーク解析クラスタ　活動実績

Cluster for M

etabolom

ic Netw

orks

30

[1] Soga et al. “Metabolomic Profiling of Anionic Metabolites by Capillary Electrophoresis Mass Spectrometry” Anal. Chem. 81:6165-6174 (2009)

[2] Ishii et al. “Multiple high throughput analyses monitor the response of E. coli to perturbations” Science 316 : 593-597 (2007)

[3] Soga et al. “Differential metabolomics reveals ophthalmic acid as an oxidative stress biomarker indicating hepatic glutathione consumption” J. Biol. Chem. 281:16768-16776 (2006)

[4] Soga et al. “Serum Metabolomics Reveals g-Gutamyl dipeptides as Biomarkers for Discrimination among Different Forms of Liver Disease.” J. Hepatol。55:896-905 (2011)

[5] Sugimoto et al . “Capil lary electrophoresis mass spectrometry-based saliva metabolomics identified oral, breast and pancreatic cancer-specific profiles” Metabolomics 6:78-95 (2009)

[6] Kinoshita et al. “Roles of Hemoglobin Allostery in Hypoxia-induced Metabolic Alterations in Erythrocytes: SIMULATION AND ITS VERIFICATION BY METABOLOME ANALYSIS” J. Biol. Chem. 282: 10731-107341(2007)

[7] Nishino et al. “In silico modeling and metabolome analysis of long-stored erythrocytes to improve blood storage methods” J. Biotech 144:212-223 (2009)

[8] Hirayama et al. “Quantitative metabolome profiling of colon and stomach cancer microenvironment by capillary electrophoresis time-of-flight mass spectrometry” Cancer Res 69:4918-25 (2009)

[9] Sugimoto et al. “Metabolomic Profiles and Sensory Attributes of Edamame under Various Storage Duration and Temperature Conditions.” J. Agric Food Chem. 58:8418-8425(2010)

[10] Sugimoto et al. “Correlation between Sensory Evaluation Scores of Japanese Sake and Metabolome Profiles” J. Agric. FoodChem 58:374-383 (2009)

慶應大学工学部卒業後渡米。カーネギーメロン大学修士課程および博士課程修了。Ph.D（情報科学）。同大学助教授、準教授歴任。その後京都大学より工学博士（電気工学）、慶應大学より医学博士（分子生物学）を取得。1990 年より慶應大学環境情報学部助教授、教授。2001年より慶應大学先端生命科学研究所（山形県鶴岡市）所長。2005 年～ 2007 年、慶應大学環境情報学部学部長。米国立科学財団・大統領奨励賞（1988）、日本ＩＢＭ科学賞（2002）、国際メタボローム学会功労賞（2009）など受賞。

ProfessorFaculty of Environment and Information StudiesDirectorInstitute for Advanced Biosciences, Keio University

慶應義塾大学環境情報学部教授慶應義塾大学先端生命科学研究所所長

Masaru Tomita冨田　勝

REFERENCES

01_事業推進担当者.indd 30 12/01/26 16:10

代謝ネットワーク解析クラスタ C l u s t e r f o r M e t a b o l o m i c N e t w o r k s31

IVV Analysis of Protein-Protein Interactions (PPIs) related to Human Metabolisms

　An ant ib iot ic puromycin is a st ructural analog of aminoacylated-tRNA, and it participates in peptide-bond formation of the nascent polypeptide chain on ribosome. At very low concentration in a cell-free translation system, puromycin is transferred specifically to the C-terminal end of the full-length protein. Based on the property, we have developed an mRNA display system named 'in vitro virus (IVV)', in which each cell-free translated polypeptide in a library covalently binds to its corresponding mRNA through puromycin (Fig. 1). After affi nity selection via the protein portion of an mRNA-displayed protein library, selected proteins can be easily identified by amplification and sequencing of the mRNA portion (Fig. 2). Moreover, IVV mRNA display based on cell-free translation can handle a larger number of molecules (approximately 1013) than the other cell-based display technique such as phage display, and it makes possible enrichment of active sequences with low abundance from a library with high diversity and complexity.

　The same property of puromycin has also been utilized to develop a highly specifi c labeling system for proteins (Fig. 3). Although recent advances in fl uorescence-based technologies, such as protein microarrays, have made it possible to analyze more than 10,000 proteins at once, there is a bottleneck in the step of preparation of a large number of fl uorescently labeled

proteins for the comprehensive PPI analysis. We developed a method for high-throughput fluorescence-labeling of full-length cDNA products at their C-termini in a translation system containing fl uorescent puromycin.

　Although the IVV mRNA display is a powerful screening tool for PPI analysis, the fi nal cloning and sequencing processes represent a bottleneck, resulting in many false negatives. To overcome this problem, we adopted tiling array technology as well as next-generation sequencer to analyze cDNA fragments from the IVV selection. The use of the tiling arrays greatly increased the coverage of known binders without reducing the accuracy. Further, this method could detect even targets with extremely low expression levels (less than a single mRNA copy per cell in whole tissue). This highly sensitive and reliable method should be useful for high-throughput PPI analysis on a genome-wide scale.　The IVV mRNA display can also be used for isolating monoclonal antibodies from recombinant antibody libraries. However, it requires several rounds of affinity selection, which is time-consuming. We combined mRNA display with a microfluidic system and achieved ultrahigh enrichment efficiency of 106- to 108- fold per round. After only one or two rounds of selection, antibodies with high affinity and specifi city were obtained from naive and mutated single-chain antibody libraries. Further we confi rmed that not only protein-protein (antigen-antibody) interactions, but also protein-DNA and protein-drug interactions were selected with ultrahigh efficiencies. This method will facilitate high-throughput preparation of antibodies and identifi cation of PPIs. We also developed a different type of totally in vitro method, DNA display, which is applicable to heterodimeric Fab fragments. Since DNA display has all advantages of both phage display and mRNA display, it represents a new option for many applications.

I. Development of Puromycin Technologies for Proteomics

01_事業推進担当者.indd 31 12/01/26 16:10

Global COE Program

代謝ネットワーク解析クラスタ　活動実績

Cluster for M

etabolom

ic Netw

orks

32

　First we performed a large-scale PPI analysis using mRNA display for 50 human transcription factors (TFs). Consequently, the data set includes 943 PPIs (Fig. 4) with a verifi cation rate of 70%. Further we found that the interacting regions (IRs) were preferentially associated with intrinsic disorder, supporting the hypothesis that vintrinsically disordered regions play a major role in the dynamics and diversity of TF networks through their ability to structurally adapt to and bind with multiple partners.

　Remodeling of glucose metabolism is associated with various biological phenomena, and is strictly regulated. A previous study showed that carbon monoxide (CO) treatment for cultured cells induces redirection of glucose flux from glycolytic pathway to pentose phosphate pathway. We focused on a rate-limiting enzyme of glycolytic pathway, TIGAR (Tp53 induced glycolysis and apoptosis regulator), whose expression may be controlled by some RNA-binding proteins through post-transcriptional regulation after CO treatment. We performed affi nity selection of proteins that bind to the 3'-UTR of TIGAR mRNA, and identifi ed two candidates for translational regulators of the enzyme that altered the binding activity for the TIGAR mRNA after CO treatment.　Musashi1 (Msi1) is an RNA-binding protein that is highly expressed in neural stem cells, and is considered to be a stemness factor. Although the basic mechanism and some target RNAs have been reported, further survey of interactors is necessary to understand the integrated function of Msi1. By using IVV mRNA display, we found that doublecortin (dcx) mRNA is a specifi c binding target of Msi1, and confi rmed that Msi1 repressed translation of a luciferase reporter gene linked to the selected 3'-UTR fragment of dcx in Neuro2A cells.

　Disease-related PPIs such as MDM2-p53 and Bcl-XL-Bak interactions are potential target for anticancer drug discovery. By using mRNA display, we performed selection of MDM2-binding and Bcl-XL-binding peptides from large random peptide libraries. We successfully identifi ed peptides that inhibit the target PPIs and thereby induce cell death. These results show that IVV selection is useful for the rapid identifi cation of potent peptides that target oncoproteins from a random peptide library.

　The frequency of occurrence of functional sequences in a random peptide library may be increased by reducing the amino-acid alphabet in the library. We performed IVV selection of a functional SH3 domain as a model from partially randomized libraries with different sets of amino acids. The results suggest that the protein sequence space with a limited set of amino acids includes a larger number of functional sequences than that with the current 20 amino-acid alphabet.

II. IVV Analysis of PPI Networks

III. IVV Selection of Peptide Inhibitors for PPIs

1974 年 3 月東北大学大学院理学研究科博士課程化学専攻修了、理学博士 ／同年 4 月 三菱化成生命科学研究所入社 ／ 1993 年 4 月 同研究所・副主任研究員、主任研究員を経て室長 ／ 2000 年 4 月 慶應義塾大学理工学部・教授／ 2002 年 10 月 21 世紀 COE「システム生物学による生命機能の理解と制御」拠点リーダー ／ 2010 年 3 月 慶應義塾大学理工学部定年退職

Visiting ProfessorFaculty of Science and Technology, Keio University

Associate ProfessorCenter for Biosciences and Informatics, School of Fundamental Science and TechnologyFaculty of Science and Technology, Keio University

Hiroshi Yanagawa柳川　弘志

慶應義塾大学理工学部訪問教授

慶應義塾大学理工学部基礎理工学専攻生命システム情報専修准教授1997 年 3 月 北海道大学大学院地球環境科学研究科博士課程修了、博士

号取得／ 同年 4 月 三菱化学生命科学研究所・特別研究員 ／ 2000 年 4 月 慶應義塾大学理工学部・助手 ／ 2003 年 4 月 慶應義塾大学理工学部・専任講師 ／ 2008 年 4 月 慶應義塾大学理工学部・准教授

PROFILE

PROFILE

Nobuhide Doi土居　信英

01_事業推進担当者.indd 32 12/01/26 16:10

代謝ネットワーク解析クラスタ C l u s t e r f o r M e t a b o l o m i c N e t w o r k s33

■ Research activities　 In this program, we have mainly invest igated two important issues: protein post-translational modifications and metabolomic analyses by imaging mass spectrometry or mass microscope.　One of the biggest findings on the first year is that a post-translational modification of tubulin regulates axonal determination through navigating a molecular motor, kinesin-1, into axon (Konishi and Setou, 2009). We also revealed that a novel ubiquitin ligase, Fbxo45, down-regulated synaptic transmission through the degradation of a synaptic vesicle-priming factor, Munc13-1 (Tada et al., 2010). A big advance in imaging mass spectrometry is that we succeeded in detecting volatile small molecules with atmospheric pressure mass microscope that we have recently developed through collaboration with Shimadzu Corporation (Harada et al., 2009).　In the second year, we reported two important findings regarding tubul in modif icat ions, and offered a new methodology for lipidomics with imaging mass spectrometry. We clarified that tubulin glutamylation is required for airway cilia to properly function (Ikegami et al., 2010). Of note, we indentified, for the first time in the world, enzymes that reverse tubulin glutamylation (Kimura et al., 2010). The developed new method for imaging mass spectrometry is ion matrix-based mass spectrometry, by which we are able to detect many phospholipids in liver and brain with high S/N ratio (Shrivas et al., 2010).　In the last year, we focused attention on imaging mass spectrometry, and analyzed the human brain samples. First, we developed a nanotechnology-based novel method to analyze small molecules in imaging mass spectrometry (Shrivas et al., 2011). We detected many small metabolites from the mouse brain. Secondly, we succeeded in visualizing spatiotemporal energy dynamics in the brain with seizure induced by kainite by means of imaging mass spectrometry in combination with CE-MS (Sugiura et al., 2011). In the kainite-induced seizure, the energy charge that can be calculated from ratio of ATP to ADP and AMP was locally lost only in the CA3 region of hippocampus (Fig. 1). Finally we studied human brains. We revealed the distinct distributions of non-hydroxylated and hydroxylated sulfatides in the human cerebral cortex (Yuki et al., 2011). Hydroxylated sulfatides are dominant in the gray matter of cerebral cortext compared to non-hydroxylated sulfatides (Fig. 2).　In conclusion, we developed some new methods to effectively perform metabolomic analyses with imaging mass spectrometry, found many important findings on the protein modifications, and revealed metabolic dynamics in the brain including the human brain.

■ Educational activities　During the program, we educated many young talented scientists. Those people received many awards, and some got principal investigator (PI) or tenured positions. Yoshiyuki Konishi got the Distingished Young Investigator Award from the

What did we do in this G-COE program?

Application of imaging mass spectrometry to visualize the aging-related changes of metabolites in vivo

01_事業推進担当者.indd 33 12/01/26 16:10

Global COE Program

PROFILE

代謝ネットワーク解析クラスタ　活動実績

Cluster for M

etabolom

ic Netw

orks

34

　We are continuing to analyze small metabolites including lipids, peptides, and nucleotides in a variety of human diseases by means of imaging mass spectrometry. The samples we examine range from liver cancer, breast cancer, abdominal aortic aneurysm, and small intestine inflammation,

to brain tissues from patients of neurodegenerative diseases or psychiatric disorders. In particular, our research interests focus on seeking out new biomarkers to detect circulating tumor cells by using mass microscope.

　We would be grateful for the support from this G-COE program.

Current our research activities

Sentiments on this G-COE program

Japanese Society for Neurochemistry 2010, and became PI and tenured associate professor at Fukui University. Nobuhiro Zaima was awarded from Japan Oil Chemists’ Society for his publications in J. Oleo Sci., and got a position of tenured assistant professor at Kinki University. Naoko Inoue also received awards from Japan Oil Chemists’ Society and The Japanese Society of Carbohydrate Research. Yuki Sugiura, who was a graduate student 2009, was awarded for his excellent presentation in the Japanese Society for Biomedical Mass Spectrometry, and became the youngest PI of JST PRESTO program.　We also have educated many foreign post-docs and students with the support of this G-COE program. Kamlesh Shrivas wrote two important papers (Anal Chem, 2010, 2011), and got assistant professor position to have his own laboratory in his home country India this summer. Cecilia Eriksson, who joined our laboratory in winter 2010, got a fellowship from Swedish government (VINNOVA), and will continue collaborations between Sweden and Japan. Piyachat Chansela, who was from Thailand, wrote a report about peptidomics by means of imaging mass spectrometry, and will receive PhD soon in Thailand. Currently, two Pakistani, one Thai, and one Vietnamese student are foreign students in our laboratory. Our laboratory has been really ‘global’ in support of this G-COE program.

■ Awards 1. 池上浩司助教が日本細胞生物学会 若手最優秀発表賞を受賞（2009/6）

2. 杉浦悠毅が日本医用マススペクトル学会ベストポスター賞を受賞（2009/9）

3. 財満信宏助教が日本油化学会ヤングフェロー賞を受賞（2009/9）

4. 瀬藤光利教授が日本臨床分子形態学会奨励賞を受賞（2009/9）

5. 財満信宏助教が JOCS-ILSI Japan Joint Symposiumにて優秀ポスター賞を受賞（2009/11）

6. 財満信宏助教、早坂孝宏助教、井上菜穂子助教、瀬藤光利教授の論文「Imaging of metabolites by MALDI mass spectrometry」が J. Oleo Sci.エディター賞を受賞（2010/4）

7. 井上助教が第 29回日本糖質学会年会ポスター賞を受賞（2010/8）

8. 小西准教授が日本神経化学会最優秀奨励賞を受賞（2010/9）

9. 井上助教が日本油化学会ヤングフェロー賞を受賞（2010/9）

10. 榎元特任研究員が日本農芸化学会 2011年度大会トピックス賞を受賞（2011/3）

11. 財満助教（2011/4/1より近畿大学農学部　応用生命科学科講師）が、J. Oleo Sci.第6回インパクト賞を受賞（2011/4）

■ Press 1. 高機能顕微鏡　分子特定、創薬を支援 　日経産業新聞、

2009年 5月 26日 2. 生体分子見ながら成分同定 　科学新聞、2009年 8月 7日 3. 生体組織分子を高解像度分析　質量顕微鏡開発に成功 　中部経済新聞、2009年 10月 29日

4. 生体組織の分子の位置特定 　中日新聞、2009年 11月 7日 5. 質量顕微鏡に英文教科書 　中日新聞、2010年 2月 23日 6. ガンダム色の遊び心 　　読売新聞、2010年 2月 25日 7. 繊毛の働き　酵素関与　　中日新聞　2010年 5月 27日 8. 繊毛の働き、酵素が調節　　静岡新聞　2010年 5月 27日 9. 繊毛の新酵素発見　　静岡新聞　2010年 6月 11日10. グルタミン酸の鎖外す酵素発見　　中日新聞　2010年 6月 13日

11. 加齢で変化する毛髪の分子特定　　中日新聞　2011年 10月 25日

12. 髪の分子　年齢変化分析　　静岡新聞　2011年 10月 26日13. 加齢による毛髪変化　　科学新聞　2011年 11月 4日

1994 年 東京大学医学部医学科卒 1996 年 同上臨床研修終了、大学院入学 1998 年 大学院中退、廣川研助手採用 2003 年 自然科学研究機構生理学研究所 助教授 2008 年 浜松医科大学 分子解剖学研究部門 教授 2011 年 浜松医科大学 解剖学講座 細胞生物学分野、

メディカルホトニクス研究センター システム分子解剖部門 兼任

ProfessorCell Biology and AnatomyHamamatsu University School of Medicine

浜松医科大学　解剖学講座 細胞生物学分野教授

Mitsutoshi Setou瀬藤　光利

01_事業推進担当者.indd 34 12/01/26 16:10