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Osaka University
Research Institute for Microbial Diseases

Research Theme :
Analyses of Protozoan infection and the molecular basis of host response
Principal Research Scientist
Toshihiro Horii
Profile:
Research:
1980 – 1996 Osaka University, Faculty of Science
[Research and achievements] Structure-function correlation of RecA protein (elucidated
the mechanism of regulation of SOS function).

1992 – 1997 Research Institute for Microbial Diseases, Osaka University
[Research and achievements] Homologous DNA recombination in eukaryotes (successfully constructed in vitro DNA recombinants).

1992 – present Research Institute for Microbial Diseases, Osaka University
[Research and achievements] Developed a Malaria vaccine using recombinant protein
(elucidated the mechanism of action of antibodies elicited by the vaccine and proved a
correlation with human protective antibody). Developed an anti-malarial drug using
computer drug design (discovered a novel lead compound).

1996 – present Research Institute for Microbial Diseases, Osaka University
[Research and achievements] Research on plasmodial prostaglandin production
(demonstrated PG production in Plasmodium falciparum). Research on host-parasite
interactions during Plasmodium falciparum infection (elucidated the structure of the host essential factor).
Education:
From 1991 Osaka University, Faculty of Medicine, Parasitology; Osaka University Graduate School of Medicine, Molecular Pathology (Molecular Protozoology)
Visiting lecturer at Hokkaido University, School of Medicine, University of Tokyo, Faculty of Medicine, Mie University, School of Medicine, Niigata University, Faculty of Medicine, Asahikawa Medical College, Aichi Medical University, and Kyushu University, Faculty of Medicine
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Collaborators

Toshihide Mitamura, Li Jie, Nirianne M.Q. Palacpac, Nobuko Arisue, Dan Sato
(Research Institute for Microbial Diseases)
Sayaka Aoki, Leung Wai Yin (Graduate School of Medicine)

Nirianne Marie Q. Palacpac (Research Associate of COE)

Cooperation given by
Masahide Ishibashi, Toyokazu Ishikawa, Hiroki Shirai, Osamu Tanishita
(The Research Foundation for Microbial Diseases of Osaka University, Kanonji Laboratory) Fumihiko Kawamoto (Institute of Scientific Research, Oita University)
Thomas G. Egwang (Med Biotech Laboratories, UGANDA))
Khin Lin (Myanmar Ministry of Health, MYANMAR)
Indah S. Tantular (Airlangga University, INDONESIA)
Pierre Druilhe (The Pasteur Institute, FRANCE)
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Research Summary
Malaria is the most threatening parasite-borne disease and causes two million deaths annually. More than 40% of the world’s population lives in malaria-epidemic regions. The emergence of drug-resistant malaria parasites has been reported throughout the epidemic regions, making malaria control extremely difficult. Therefore, the development of a practical vaccine and novel anti-malarial drugs is an urgent issue for the scientific community. We are currently working toward developing a malaria vaccine and anti-malarial drugs for practical use. We are also analyzing the mechanisms by which plasmodium adapts to a new host using molecular and cell biological approaches.

(1) Development of a Malaria vaccine based on the recombinant SERA antigen
We have constructed a recombinant SE47’ protein based on the serine repeat antigen (SERA) of Plasmodium falciparum. We have demonstrated that antibodies raised against SE47’ protein aggregate plasmodial schizonts and merozoites. We have also found that natural anti-malaria immunity acquired by people who live in highly endemic malarial areas is due to anti-SE47’ IgG3 antibodies in their sera. We have completed GMP production of the improved structure of the recombinant SE36 protein at the Research Foundation of Microbial Diseases, Osaka University, Kanonji Laboratory and a pre-clinical study of this protein is underway. A phase I clinical trial will be undertaken in the next year, with aiming a phase II clinical trials in the following year in malarial epidemic areas (such as Uganda, Myanmar, and Indonesia).


(2) Intraerythrocytic proliferation of Plasmodium falciparum and the molecular mechanisms of lipid metabolism/trafficking within Plasmodium falciparum-infected erythrocytes
Our current research is focused on: 1) Investigating the metabolites of a specific combination of saturated/unsaturated fatty acids (the combination of palmitic and oleic acids is optimal), which in association with serum albumin, has shown to be among serum essential factors for proliferation of Plasmodium falciparum during intraerythrocytic cycle, a direct cause of symptoms of malaria. 2) Identification of the plasmodial factor(s) involved in the metabolism and trafficking of these lipids. 3) Elucidation of the molecular mechanisms of metabolism and trafficking of these lipids in P. falciparum-infected erythrocyte. In this project, we seek to investigate a unique biological phenomenon in P. falciparum-infected erythrocytes, aiming to provide a novel target for malaria chemotherapy.
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Publications

1. Safitri I., Jalloh A., Tantular I. S., Pusarawati S., Win T.T., Liu Q., Ferreira M. U.,
Dachlan Y.P., Horii T. and Kawamoto F. Sequence diversity in the amino-terminal region of the malaria-vaccine candidate serine repeat antigen (SERA) in natural Plasmodium falciparum populations. Parasitol. Int. 52, 117 – 131, 2003

2. Mitamura T. and Palacpac N. M. Q. Lipid metabolism in Plasmodium falciparum-
infected erythrocyte: possible new targets for malaria chemotherapy. Microbes Infect. 5; 545-552, 2003

3. Soe S., Singh S., Camus D., Horii T., Druilhe P. Plasmodium falciparum serine repeat
protein, a new target of monocyte-dependent antibody-mediated parasite killing. Infect. Immun. 70, 7182-7184, 2002

4. Aoki S., Li J., Itagaki S., Okech B.A., Egwang T.G., Matsuoka H., Nirianne M. Q.,
Mitamura T. and Horii T. SERA (SERA5) is predominantly expressed among the SERA multigene family of Plasmodium falciparum and the acquired antibody titers correlate with serum inhibition of the parasite growth. J. Biol. Chem. 277, 47533-47540, 2002

5. Li J., Mitamura T., Pang X.L., Fox B.A., Bzik D.J. and Horii T. Differential localization
of processed fragments of Plsmodium falciparum serine repeat antigen (SERA) . Parasitol. Int. 51,343-352,2002

6. Li J., Matsuoka H., Mitamura T. and Horii T. Characterization of proteases involved in
the processing of Plasmodium falciparum serine repeat antigen (SERA) Mol. Biochem. Parsitol. 120, 177-186, 2002.

7. Okech B.A., Nalunkuma A., Okello D., Pang X.L., Suzue K., Li J., Horii T., and
Egwang T.G. Natural human IgG subclass responses to Plasmodium falciparum serine repeat antigen (SERA) in Uganda. Am. J. Trop. Med. Hyg. 65:912-917, 2001
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