Juntendo University, Tokyo, established in 1838.

Associate Professor : Shinzaburo Takamiya, Takeshi Nara, Muneaki Hashimoto
Assistant Professor: Akiko Tsubouchi, Jorge Morales
Researcher: Shigeo Suzuki

Visiting Professor : Anthony T. Tu, Hiroshi Ohmae
Professor Emeritus: Takashi Aoki
Visiting Researcher: Hiroshi Yamasaki

Neglected tropical diseases are a group of communicable diseases, which thrive in impoverished settings and blight the lives of around one billion people worldwide, while threatening the health of millions more. Of the main seventeen neglected diseases, ten diseases occur as the parasitic infections (First WHO report on neglected tropical diseases, 2010).

Our group has focused on molecular biological, biochemical, and phylogenetic aspects of the parasitic eukaryotes in terms of elucidating the nature of parasitism. In addition, international and socio-medical studies for managing the communicable diseases with high risks, including highly pathogenic avian influenza, HIV/AIDS, and opportunistic infections have been recently conducted.

The members of our group have a variety of skills ranging from cell biology, molecular biology, phylogenetics biochemistry and social sciences including law and economics. We have a good mix of academic backgrounds in our group, which makes a friendly, supportive and multicultural work environment.

Importantly, our group has an excellent ability for education in research; since 2000, nine Ph.D. students including two foreign students have left the nest and published their thesis in the authorized international journals such as J Mol Biol, Mol Biol Cell, J Mol Evol, Protist, Gene, Biochim Biophys Acta, Mol Biochem Parasitol, and Trop Med Health. Undergraduate students are also welcome to join our research and can be encouraged to challenge the national award hosted by the Japanese Government (http://www.science-i.jp/index.html).

Further information can be obtained by contacting Takeshi (e-mail: tnara@Juntendo.ac.jp). Let's join us!

Chagas Disease

Chagas disease is the typical neglected tropical disease endemic in Latin American countries (1) and often in North America, Europe, Japan, and Australia where the immigrants from the endemic countries dwell in. The etiologic agent is the parasitic protist, Trypanosoma cruzi (2), which can be transmitted by the insect vector, an assassin bug (3), transfusion, and via placenta and finally parasitizes inside the human cell (4). Our investigations are aimed at elucidating the nature of parasitism and the host-parasite relationship at the molecular and cellular levels, by means of finely tuned, advanced biotechnology tools such as genetic modification of the parasite (5) and crystallography (6).
    Individual topics are listed below.

The evolutionary trail of metabolic pathways in parasitism

(Correspondence to Jorge and Takeshi)
All of the parasites have been preceded by the free-living ancestors. Trypanosomatids including T. cruzi belong to the eukaryotic group, Euglenozoa, which includes the early branching free-living euglenoids, such as photosynthetic Euglena, and diplonemids. We are investigating the evolutionary events that have led to the establishment of the unique metabolism found in trypanosomatids be means of biochemical, metabolomic and genomic analyses in Euglenozoa.

Intracellular parasitism of Trypanosoma cruzi

(Correspondence to Muneaki)
Parasites often manipulate and hijack the biological system of host cells in order to create their suitable environment for their survival and proliferation. T. cruzi is found to represent them by our research. We are investigating molecular mechanism in the process of attachment, invasion, and proliferation between T. cruzi and the host cells in vitro and in vivo.

Anaerobic adaptation for parasitism

(Correspondence to Shinzaburo)
Parasites often dwell and reproduce in the extremely low oxygen environment, such as in the intestinal tract, via migration from the atmospheric conditions at the larval stages. We are investigating the molecular mechanism of anaerobic adaptation. In particular, we are focusing on the parasite-specific energy metabolism in the mitochondrial respiratory chain and enzymes for oxygen metabolism in roundworm, lungworm, tapeworm and C. elegans as a model.

Drug development for neglected diseases

(Correspondence to Shigeo and Takeshi)
Drug development for Chagas disease is of urgent need because of the lack of drugs with high effectiveness, low toxicity and low cost. We are fighting to discover lead compounds required for drug development against Chagas disease. Remarkably, the promising compounds are found in brown algae, which inhibit dihydroorotate dehydrogenase, the fourth enzyme of the de novo pyrimidine biosynthesis, as well as intracellular growth of T. cruzi. Our investigations are aimed at determining the structure of these DHOD inhibitors for further structure-based drug design.

Controlling emerging and re-emerging infectious diseases: Relationships between risk assessment and human behavior

(Correspondence to Akiko)
Our investigations are aimed at establishing 1) a system for minimizing damages physically, socially, and economically and 2) the reliable and suitable measures for the management of emerging and re-emerging infectious diseases, especially highly pathogenic avian influenza (HPAI H5N1) and HIV/AIDS infection. Quarantine of individual patients and insulation of the human migration are recognized as the more effective control measures during outbreak of SARS in the absence of prophylaxis and chemotherapy. To achieve this, knowledge management is a most effective tool in low cost to refuge from dangerous infectious diseases. Therefore, we are interested in risk assessment and risk communication for ordinary people and education for school children before the outbreak.

   Risk communication and education play pivotal roles for accurate information transmission, otherwise risks increase and lead to the outbreak. Our goal is to establish a “Global Standard” as the educational method for infectious disease control and offer the suggestion with it to WHO.

Intelligence and information innovation management in the clinical scenes

(Correspondence to Akiko)
‘Risk Assessment’ and ‘Risk Communication’ are essential in the clinical scenes. Inadequate management has led to the rapid increase of the communication-associated medical accidents and incidents. Our investigation is aimed at establishing and introducing more suitable and valuable measures in Risk Assessment and Risk Communication in the clinical scenes, in close cooperation with non-governmental organizations and student study group (http://iryotohouritsu.web.fc2.com/).

(*Corresponding author)

2011

1. Liao CW, Sukati H, Nara T, Tsubouchi A, Chou CM, Jian JY, Huang YC, Chang WS, Chiu WT, Huang YH Fan CK. Prevalence of Schistosoma haematobium infection among schoolchildren in remote areas devoid of sanitation in Northwestern Swaziland, Southern Africa. Jap J Inf Dis, in press
2. Chu TB, Liao CW, Nara T, Huang YC, Chou CM, Liu YH, Fan CK. Enterobius vermicularis infection is well controlled among preschool children in nurseries of Taipei City, Taiwan. Rev Soc Bras Med Trop, in press
3. Tsubouchi A (2011) 'Knowledge Management' as Highly Pathogenic Influenza Control, Annuals. ARIMASS, in press
4. Tajima K, Miura K, Ishiwata T, Takahashi F, Yoshioka M, Minakata K, Murakami A, Sasaki S, Iwakami S, Annoura T, Hashimoto M, Nara T, Takahashi K. (2011) Sex hormones alter Th1 responses and enhance granuloma formation in the lung. Respiration, 81:491-498
5. Makiuchi T, Annoura T, Hashimoto M, Hashimoto T, Aoki T, Nara T*. (2011) Compartmentalization of a glycolytic enzyme in Diplonema, a non-kinetoplastid Euglenozoan. Protist, 162:482-489

2010

1. Takamiya S, Fukuda K, Nakamura T, Aoki T. Sugiyama H. Paragonimus westermani possesses aerobic and anaerobic mitochondria in different tissues, adapting to fluctuating oxygen tension.Proceedings of 12th International Congress of Parasitology ICOPA XI, 2010, pp.129-135, MEDIMOND S.r.l., Bologna, Italy.
2. Tajima K, Ohashi R, Sekido Y, Hida T, Nara T, Hashimoto M, Iwakami S, Minakata K, Yae T, Takahashi F, Saya H, Takahashi K. (2010) Osteopontin-mediated enhanced hyaluronan binding induces multidrug resistance in mesothelioma cells. Oncogene, 29(13): 1941-1951
3. Kohama H, Harakuni T, Kikuchi M, Nara T, Takemura Y, Miyata T, Sato Y, Hirayama K, Arakawa T. (2010) Intranasal administration of Schistosoma japonicum paramyosin induced robust long-lasting systemic and local antibody as well as delayed-type hypersensitivity responses, but failed to confer protection in a mouse infection model. Jap J Inf Dis, 63(3): 166-172
4. Takamiya S, Fukuda K, Nakamura T, Aoki T, Sugiyama H. (2010) Paragonimus westermani possesses aerobic and anaerobic mitochondria in different tissues, adapting to fluctuating oxygen tension in microaerobic habitats. Int J Parasitol, 40: 1651-1658
5. Kido Y, Shiba T, Inaoka DK, Sakamoto K, Nara T, Aoki T, Honma T, Tanaka A, Inoue M, Matsuoka S, Moore A, Harada S, Kita K. (2010) Crystallization and preliminary crystallographic analysis of cyanide-insensitive alternative oxidase from Trypanosoma brucei brucei. Acta Crystallogr, F66: 275-278
6. Balogun EO, Inaoka DK, Kido Y, Shiba T, Nara T, Aoki T, Honma T, Tanaka A, Inoue M, Matsuoka S, Michels PAM, Harada S, Kita K. (2010) Overproduction, purification, crystallization and preliminary X-ray diffraction analysis of Trypanosoma brucei gambiense glycerol kinase. Acta Crystallogr, F66: 304-308
7. Hashimoto M*, Murata E, Aoki T (2010) Secretory protein with RING finger domain (SPRING) specific to Trypanosoma cruzi is directed, as a ubiquitin ligase related protein, to the nucleus of host cells. Cell Microbiol, 12(1):19-30
8. Tsubouchi A (2010), The Comparative study on risk communication for control of emerging and reemerging Influenza in Japan-Taiwan, Annuals ARIMASS, (suppl.): 18-29

2009

1. Takamiya S*, Hashimoto M, Kazuno S, Kikkawa M, Yamakura F. (2009) Ascaris suum NADH-methemo(myo)globin reductase systems recovering differential functions of hemoglobin and myoglobin, adapting to environmental hypoxia. Parasitol. Int, 58, 278-284
2. Bao Y, Weiss LM, Hashimoto M, Nara T, Huang H (2009) Protein kinase A regulatory subunit interacts with P-Type ATPases in Trypanosoma cruzi. Am J Trop Med Hyg, 80(6), 941-3
3. Gonmori K, Hiramatsu M, Okazaki S, Suzuki O, Tu AT (2009) Rapid nondestructive screening for melamine in dried milk by Raman spectroscopy. Forensic Toxicology, 27, 94-97
4. Komori Y, Nagamizu M, Uchiya K, Nikai T, Tu AT (2009) Isolation and Chemical Characterization of a Toxin Isolated from the Venom of the Sea Snake Hydrophis torquatus aagardi. Toxins 1, 1-11
5. Komori Y, Nagamizu M, Uchiya K, Nikai T, and Tu AT (2009) Comparison of Sea snake (Hydrophiidae) Neurotoxin to Cobra (Naja) Neurotoxin. Toxins 1, 151-61
6. Morales J, Mogi T, Mineki S, Takashima E, Mineki R, Hirawake H, Sakamoto K, Omura S, Kita K. Novel mitochondrial complex II isolated from Trypanosoma cruzi is composed of 12 peptides including a heterodimeric Ip subunit. J Biol Chem, 2009, 284(11):7255-7263

2008

1. Hashimoto M, Takamiya S*, Yokota T, Nakajima Y, Yamakura F, Sugio S, Aoki T (2008) Ascaris suum cytochrome b5, an adult-specific secretory protein reducing oxygen-avid ferric hemoglobin. Arch Biochem Biophys, 471, 42-9
2. Inaoka DK, Sakamoto K, Shimizu H, Shiba T, Kurisu G, Nara T, Aoki T, Kita K, Harada S. Structures of Trypanosoma cruzi dihydroorotate dehydrogenase complexed with substrates and products: Atomic resolution insights into mechanisms of dihydroorotate oxidation and fumarate reduction. Biochemistry, 47(41), 10881-91
3. Kakinuma Y, Iida H, Sekizuka T, Taneike I, Takamiya S, Moore JE, Millar BC, Matsuda M (2008) Molecular characterization of urease genes from urease-positive thermophilic Campylobacter (UPTC) isolates. British J. Biomed. Sci, 65, 1-5
4. Makiuchi T, Annoura T, Hashimoto T, Murata E, Aoki T, Nara T* (2008) Evolutionary analysis of synteny and gene fusion for pyrimidine biosynthetic enzymes in Euglenozoa: an extraordinary gap between kinetoplastids and diplonemids. Protist, 159, 459-70
5. Murata E, Hashimoto M*, Aoki T (2008) Interaction between cFLIPL and Itch, a ubiquitin ligase, is obstructed in Trypanosoma cruzi-infected human cells. Microbiol Immunol, 52(11), 539-43.
6. Shigihara T, Hashimoto M*, Shindo N, Aoki T (2008) Transcriptome profile of Trypanosoma cruzi-infected cells: simultaneous up- and down-regulation of proliferation inhibitors and promoters. Parasitol Res, 102, 715-22
7. Yamazaki M, Ohwada A, Miyaji A, Yamazaki H, Nara T, Hirai S, Fujii H, Uekusa T, Suzuki M, Iwase A, Takahashi K. (2008) Pulmonary Paragonimiasis with Coincidental Malignant Mesothelioma. Intern Med, 47, 1027-1031
8. Tsubouchi A (2008) A study on issues of Japanese laws should manage expanding risks of infectious diseases, Annuals ARIMASS, (suppl.):34-39

2007

1. Annoura T, Sariego I, Nara T, Makiuchi T, Fujimura T, Taka H, Mineki R, Murayama K, Aoki T* (2007) Dihydroorotate dehydrogenase arises from novel fused gene product with aspartate carbamoyltransferase in Bodo saliens. Biochem Biophys Res Commun, 358, 253-258.
2. Kakinuma Y, Iida H, Sekizuka T, Taneike I, Takamiya S, Moore J E, Millar B C, Matsuda M (2007) Cloning, sequencing and characterization of a urease gene operon from urease-positive thermophilic Campylobacter (UPTC). J Appl Microbiol, 103, 52-60
3. Kobayashi T, Sato S, Takamiya S, Komaki-Yasuda K, Yano K, Hirata A, Onitsuka I, Hata M, Mi-Ichi F, Tanaka T, Hase T, Miyajima A, Kawazu S, Watanabe Y, Kita K (2007) Mitochondria and apicoplast of Plasmodium falciparum: Behaviour on subcellular fractionation and the implication. Mitochondrion, 7, 125-32.
4. Makiuchi T, Nara T*, Annoura T, Hashimoto T, Aoki T (2007) Occurrence of multiple, independent gene fusion events for the fifth and sixth enzymes of pyrimidine biosynthesis in different eukaryotic groups. Gene, 394, 78-86
5. Mita T, Tanabe K, Takahashi N, Tsukahara T, Eto H, Dysoley L, Ohmae H, Kita K, Krudsood S, Looareesuwan S, Kaneko A, Bjorkman A, Kobayakawa T (2007) Independent evolution of pyrimethamine resistance in Plasmodium falciparum isolates in Melanesia. Antimicrob Agents Chemother, 51, 1071-1077
6. Nara T*, Iizumi K, Ohmae H, Sy OS, Tsubota S, Inaba Y, Tsubouchi A, Tanabe M, Kojima S, Aoki T (2007) Antibody isotype responses to paramyosin, a vaccine candidate for schistosomiasis, and their correlations with resistance and fibrosis in patients infected with Schistosoma japonicum in Leyte, The Philippines. Am J Trop Med Hyg, 76, 384-391
7. Shimada M, Kato-Hayashi N, Chigusa Y, Nakamura S, Ohmae H, Sinuon M, Socheat D, Kitikoon V, Matsuda H (2007) High susceptibility of Neotricula aperta gamma-strain from Krakor and Sdau in Cambodia to Schistosoma mekongi from Khong Island in Laos. Parasitol Int, 56, 157-160
8. Sinuon M, Tsuyuoka R, Socheat D, Odermatt P, Ohmae H, Matsuda H, Montresor A, Palmer K (2007) Control of Schistosoma mekongi in Cambodia: results of eight years of control activities in the two endemic provinces. Trans R Soc Trop Med Hyg, 101, 34-39
9. Tanabe K, Sakihama N, Walliker D, BabiKer H, Abdel-Muhsin AM, Bakote`e B, Ohmae H, Arisue N, Horii T, Rooth I, Farmert A, Bjorkman A, Rabford-Cartwright L. (2007) Alleric dimorphism-associated restriction of recombination in Plasmodium falciparum msp-1. Gene 397(1-2):153-60
10. Tazumi A , Saito S, Sekizuka T, Murayama O, Takamiya S, Moore J E, Millar B C, Matsuda M (2007) Molecular characterization of the full-length 23S and 5S ribosomal RNA (rRNA) genes of Taylorella asinigenitalis. Antonie van Leeuwenhoek, 92, 257-264
11. Tu AT (2007) Toxicological and chemical aspects of sarin terrorism in Japan in 1994 and 1995. Tox. Rev, 24, 143-174
12. Tsubouchi A (2007) A study on risk management through passed medical lawsuits, Annuals ARIMASS, (suppl.):33-38