Staff

NISHIKAWA Yoshifumi

Professor

Theme

Studies on mechanism of disease onset caused by infection with pathogenic protozoan parasites based on micro and macro-viewpoints for development of basic research about vaccine and drug discovery

My Dream

Study of host-manipulation mechanism by parasites

Belongs

National Research Center for Protozoan Diseases, Department of Drug Discovery and Development, Research Unit for Innovative Medicine 

Research Center for Global Agromedicine, Department of Veterinary Medicine

Faculty (Unit)

Veterinary Medicine Program

Grad school (Course)

Doctoral Program of Veterinary Science

Field of research Immunology, Infectious Disease, Parasitology, Biochemistry, Cell Biology, Molecular Biology, Veterinay Medicine
Keyword Parasite, Protozoa, Vaccine, Diagnosis, Medicine, Central Nervous System, Reproduction, Pathogenesity

Introduction

To control the pathogenic protozoan parasites, interaction between basic and applied research are required. Systematic approaches to understand disease onset mechanism of protozoan infection, develop realistic methods of treatment and prevention, grasp problems, and evaluate the efficacy in the field are needed. Our laboratory is conducting the following research.

  1. Studies on how protozoan parasites manipulate host cells
    Intracellular protozoan parasites can survive by exploiting the growth mechanisms of the host cells. For example, Toxoplasma and Neospora species actively invade nucleated mammalian cells and form parasitophorous vacuoles to evade the host immune system and appropriate host nutrients. We focus on the mechanisms of such manipulation and discover the parasite factors.
  2. Study on the mechanisms of onset for protozoan diseases
    Infection by protozoan parasites causes numerous diseases in host animals. Major examples are severe anemia from malaria, abortion and neurological disease from Toxoplasma and Neospora species, and diarrhea from Cryptosporidium. To understand the mechanism of onset for protozoan diseases, we perform pathologic analyses on experimental mice and natural host animals. We generate gene-disrupted parasites for the parasite factors mentioned above based on gene editing technologies and perform verification experiments using experimental mice.
  3. The development of vaccines and drugs for the control of protozoan diseases
    Eradicating intracellular protozoan parasites requires the induction of T cells, which can disrupt the infected cells, because antibody production induced by conventional vaccines is ineffective at killing intracellular parasites. We develop T cell induction vaccines based on vaccines that utilize antigens entrapped in multi-functional liposomes. In addition, we screen candidate drugs by using libraries of natural biological resources and chemicals from around the world in order to discover anti-protozoan drugs.
  4. The development of practical diagnostic systems for protozoan infectious diseases
    We develop practical systems for diagnosing protozoan infectious diseases in the field. We survey the prevalence of protozoan infections in Japan and developing countries and prepare specific recommendations by providing practical diagnostic systems for use in the field.
Electronic microscope picture of Toxoplasma tachyzoite. Diving two parasites are observed.
Mouse fetus on gestation day 10. In mouse infected with Toxoplasma on gestation day 3, embryos were small and folded irregularly (HE, hematoxylin and eosin) and apoptosis (Red signal in TUNEL) was observed.
Behavioral analysis on aversion of cat odor in mice. Uninfected mouse escapes from cat odor, but Toxoplasma-infected mouse decreases the aversion of cat odor.
Specific immunofluorescent staining of rodent malaria parasite in kidney. Compared to normal mouse (Normal), infected red blood cells had accumulated in the glomerular capillaries of the kidney are observed in macrophage-depleted mouse (Macrophage depleted)
RNA-seq analysis of macrophages infected with Neospora caninum, parental strain (Nc1), NcGRA7-deficient parasite (KO), or NcGRA7-complemented parasite(Comp) and uninfected cells (NoI). (Left panel) These data show the differential expression of genes associated with the presence or absence of NcGRA7. Expression of all genes in the pathway “cytokine-cytokine receptor interaction” was plotted as a heatmap. (Right panel) Principal-component analysis was performed to gain an overview all the expression data and identify classification patterns.
Bovine abortion by Neospora infection

List of current research topics

  • Study on onset mechanism of congenital toxoplasmosis for the development of novel therapy
  • Study of memory-manipulate mechanism by infection with brain parasite, Toxoplasma gondii
  • Study on brain manipulator of Toxoplasma gondii which can control central nervous system
  • Study on host- hijacking mechanism of Toxoplasma infection
  • Discovery of virulence factor of Neospora caninum and its application for vaccine development
  • Study of abortion mechanism by infection with pathogenic protozoan oparasite in livestock, Neospora caninum
  • Development of practical diagnostic method for Neospora caninum infection
  • Study on control of cryptosporidiosis by metagenomics of bovine intestinal flora
  • Development of serodiagnosis system for protozoan parasite infection in food animals and its seroepidemiological study
  • Study on comprehensive control strategy against zoonotic protozoan diseases in Southeast Asia
Academic degree D.Agr.
Room address General Research Building 4
Mail address nisikawa atmark obihiro.ac.jp

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