Mastitis is the most devastating economic burden in dairy farms. We have studied the epidemiology of acute mastitis caused by coliforms, the relationship between clinical symptoms and cytokines and acute phase proteins, and the relationship between symptoms and prognosis, and found a link. In addition, in the treatment of mastitis, it was found that the application of a lotion with antibacterial activity (Ceramella) to the inflamed udder, in addition to conventional antibiotic treatment, decreases breast induration and somatic cell count. Studies have shown that the shorter the milk is cultured, the more causative organisms are detected in bacteriological tests of milk. As for prevention of mastitis, administration of a leptospirosis vaccine has been shown to reduce clinical forms of mastitis. It was also found that the severity of symptoms of acute mastitis caused by Escherichia coli was related to the level of ionized calcium in the blood at the time of initial examination. We are studying prevention, treatment, and prognosis of mastitis in dairy cows. It was found that there is a relationship between blood physiological changes in dairy cows in response to climatic changes and stress. Based on the results of this research, we would like to further our research on improving milk productivity.

Recently, cancer is a major cause of death in companion animals, which leads to a strong need for more advanced and personalized oncological care. At the same time, naturally occuring cancers in genetically heterogenous companions animals draw significant attention in oncological research to untangle the comlexed mechanism of carcinogenesis in mammals. I have been working on carcinogenesis and malignant progression of cancer using traditional molecular biological approaches and advanced next-generation analyses including bioinformatics. I am also interested in veterinary oncologycal surgery and perioperative care.

Since the Human Genome Project completed sequencing the 3 billion bps that make up human DNA, it became clear not only that we are able to read nature’s complete genetic blueprint, but also that the information stored in the sequence of the DNA is not enough per se to completely explain development, physiology and disease. The field dedicated to decipher the heritable features that complements the genetic information stored in the DNA sequence is termed “epigenetics”.
Epigenetic regulation provide a possible link between the environment and long term alterations in gene function that might lead to disease phenotypes. Most diseases are related in some way to the loss or gain in gene functions. To reveal the cause and mechanism of chronic disease (e.g. diabetase and hypertention), we mainly focus on the interaction between nutritional condition and epigenetic alteration.

To provide sophisticated treatments as seen in human medicine to animal patients, I have strived to conduct researches in the medical institutions of orthopedic surgery.
First, clinical orthopedic researches are ongoing. The clinical image is an example of bone reconstructive surgery after removal of malignant bone sarcoma. Thus, human surgical techniques are applicable to animal patients.
Second, in musculoskeletal tumor field, the multidisciplinary treatments including particle radiation and a novel target therapy for hard-to-treat cancers are ongoing in cooperation with National Cancer Center, Ehime University Orthopedic Surgery, Hyogo Ion Beam Medical Center and Karmanos Cancer Institute. The results can contribute to the animal patients of musculoskeletal tumors with no choice of therapy.
Third, translational researches are also ongoing. The analysis of microenvironment have been complicated because millions of molecular interactions are possible. Hence, using bioinformatics technologies, a software has been constructed to visualize these numerous interactions.

Due to improvements in breeding methods and advances in veterinary medicine, the average lifespan of pets has increased dramatically. Unlike humans, animals often do not show their illness even when they are sick, and by the time they notice it, it often progresses and is difficult to treat. Advanced diagnostic imaging such as CT and MRI and various “cancer markers” are used in human medicine, but there are no “cancer markers” that can be used in veterinary medicine, and advanced diagnostic imaging requires high cost and general anesthesia. If there is a disease marker that accurately reflects the pathology of “cancer”, it will be possible for owners and patient animals to avoid the burden of anesthesia and examination, and to objectively judge the need for continuous treatment. Therefore, in recent years, we have focused on a technology called liquid biopsy, which has been attracting attention in medicine, to detect genes circulating in the blood, and we are researching its application to pet cancer. Specifically, we are investigating the usefulness of tumor pathological evaluation and diagnostic markers by measuring the amount of genes released from the tumor itself and detecting specific mutations.

1. We investgate protein with the possibility to become the prognostic index of the cancer in the animal. We especially focus on CYR61, and investigate the mechanism of the metastasis and relations with CYR61 and tumor invasion, and usability as prognositicindex of CYR61.
2. We will study methods to maintain the quality of life of postoperative animals, by dveloping new surgical methods and assisting the functions with artificail materials.
3. We will research the effect on living organism, in addition to the antitumor effect of immunotherapy.

Japanese people sleep less than most developed countries, and one out of every four to five adults has some kind of sleep problem. Sleep deprivation is known to increase the risk of developing depression, anxiety disorders, obesity, and diabetes. My research aims to elucidate the molecular mechanisms underlying these effects of sleep deprivation on the body and mind. In addition, by studying the effects of physical, chemical, psychological, and social stress on sleep homeostasis using mouse models, I aim to elucidate the molecular mechanisms underlying stress-induced sleep disorders and psychiatric disorders and to contribute to the development of preventive and therapeutic methods.

We aim to reveal the mechanism of pathogenicity on highly pathogenic viral zoonoses, using our Biosafety level 3 (BSL3) laboratory, as well as BSL4 facility in the foreign country (as a coolaborative research with Australian Animal Health laboratory, CSIRO).

So far, through a collaborative research with AAHL, we had established the reverse genetics system for nipah virus or hendra virus. By introducing mutations into the viral genome with the system, we are trying to rescue or make mutant virus and characterize the mutant virus. This approach would find or characterize nature of the original virus. Moreover, we would like to develope effective and safe vaccines for the viruses using recombinant mutant viruses.

There are numerous diseases that are difficult to diagnose and refractory to conventional treatments. I have special interests in acute kidney injury, systemic inflammatory response syndrome, sepsis, and refractory immune-mediated diseases. Currently, I am conducting researches on blood purification therapy to establish the means of treatment of these diseases.

Two major research themes have been addressed. The first is the identification of novel pathogens and the development of disease control methods for fish and shellfish. In aquaculture farms, mortality caused by unidentified diseases is often observed. The causative factors are quite complex including deterioration of the environment, nutritional disorders, and outbreak of infectious diseases. With recent advances in aquaculture technology, the targeted species for aquaculture have expanded, and new infectious diseases have been reported one after another. Therefore, we are exploring the pathogens using a comprehensive genetics approach to develop the diagnosis methods and control the diseases. Second, we are also studying the unique immune system in shrimp. As invertebrates, shrimp have no adaptive immune system like vertebrates. However, they show some resistance to re-infection of particular pathogen, like a phenomenon known as “immunological memory”. We hope to elucidate the mechanism of this phenomenon and propose new disease control measures to improve productivity.

Vision is indispensable sense “veterinary ophthalmology”, as visual information obtained by seeing the objects is important for us.
However, the “visual acuity” examination using the Landolt’s ring like a human (mark like “C” in the alphabet) is impossible in dogs and cats and other animals. So how do you determine the animal’s visual acuity?
One method is to measure brain waves called “visual evoked potentials (VEP)” and evaluate whether the brain recognized the targets.
We are developing “Visual Evaluation Methods of Animals” using “electrophysiological exams of vision”, including VEP measurement.
We suppose that highly accurate visual assessment of animals will allow us to better diagnose and treat ophthalmic disorders in areas essential to constitute the vision of the cornea, lens, retina, etc. in the eye.

In addition, our laboratory uses ophthalmologic examination equipment such as Optical Coherence Tomography (OCT), which has developed remarkably in recent years, in clinical veterinary ophthalmology, and is conducting research on the pathophysiological analysis and treatments of ophthalmologic diseases.

We have identified the bovine major histocompatibility gene complex (BoLA) alleles resistant and susceptible for BLV in five tethered house farms in the Kanto region of Japan, and we have conducted the BLV control strategy using resistant and susceptible cattle. In the future, I would like to conduct the strategy utilizing resistant and susceptible cattle in more tethered farms and futhermore in free-ban and free-stall farms.
In the project for control of tuberculosis and glanders, we focused on tuberculosis and glanders, zoonotic bacterial infections prevalent in Mongolia, and the veterinary and medical researchers in Japan and Mongolia are collaborating on this project to conduct epidemiological surveys and develop rapid diagnostic methods for these both diseases.
In addition, I will conduct a study for genetic diversity of Asian native horses.

More than 200 herpesviruses have been discovered and most of them have very limited host range. Therefore, there are many herpesviruses which have not established cell culture system to replicate or system to evaluate the pathogenicity of the virus using experimental animals. Without these systems it is impossible to analyze the precise mechanism of viral replication and pathogenicity. Thus, I aim to unveil the determination mechanism of host specificity of herpesvirus by analyzing the interactions of virus and host factors by using recombinant viruses. In addition, I also study epidemiology of herpesviruses.

As SFTS virus seems to be spread in Ehime, our lab focuses on SFTS virus. I compare the pathogenicity of SFTS virus and its related virus, Heartland virus and analyze which factor causes the difference.

I analyze influences of biogeographic phenomena such as evolution and migration of host animals on parasite distribution or population using molecular phylogenetic analyses. I’m also conducting research on the mechanisms of migration and pathology of helminths in their host.

In dogs and cats, morbidity of heart disease is very high. My research are investigation of the pathology, examination of new therapy and the methods of early diagnosis.

In Imaging diagnosis of veterinary, The development of diagnostic imaging apparatuses is remarkable. Cntast CT and contast ultrasound were applied to the differential diagnosis of lhepatic and splenic tumors. In MRI, various special methods are used for the application of diagnosis tiool of various disease. I study the new image diagostic tool and determining the most suitable imaging method of various diseases.

Rheumatoid arthritis (RA) is a disease based on chronic inflammation in synovium. Since RA is a relatively common disease in human, there are many studies on its pathogenesis, and recently we can control RA with biological drugs or small molecular compounds. Dogs may develop a disease similar to that of human, also known as canine rheumatoid arthritis (cRA). However, since there are few studies on its pathophysiology, most dogs with cRA take only symptomatic treatment, and joint structures are irrevocably destroyed. I am studying to elucidate the inducer of inflammation in cRA, identification of early diagnostic marker, and development of new therapeutic drug.
I am also studying the Wnt5a antagonist Sfrp5. Sfrp5 is an adipokine that regulates the metabolism of adipocytes. We already found that Sfrp5 regulates not only adipocytes but also osteoblasts and osteoclasts. In other words, fat tissue may control bone. I am studying the mechanisms how Sfrp5 regulates bone.

Smooth muscle composes a muscular layer in various organs, such as blood vessels, gastrointestinal tracts, bladder, uterus, etc. in the vertablate body. It plays important roles in many life stages from birth to death. To achieve different roles in different locations, each smooth muscle has unique regulatory mechanisms of contraction and relaxation. For example, renal arteriolar smooth muscle, which regulates blood flow in the kidney, contracts in response to a vasoconstrictor, angiotensin II by activating molecular motor in the cells. On the other hand, another vasoconstrictor, endothelin 1, induces abnormal contraction in the arteriole by excessively activating the motor. I hve been studying the molecular mechanisms of smooth muscle contractions, especilly in the renal arterioles.

To explore my interest using a molecular biology approach, we employ novel transgenic animal models and ex vivo or in vitro systems such as isolated vessel and cell culture.
Cardiovascular disease is a major cause of mortality. In particular, the prevalence of hypertension is high and increasing (American Heart Association). To understand the mechanism of outbreak and molecular alterations in hypertension, we examine how genes regulate organ function related to regulating blood pressure including vessel, heart, kidney and brain using transgenic model.
Gut microbiome research is becoming the key to better understanding physiology and pathology. Clinical evidence is accumulating for a role of the microbiome in contributing to aging and inflammtory disorder. We try to find how microbiome affects body.

Reproductive disorders in cows are major health and financial problems on farm. Endometritis and ovarian dysfunction such as cystic ovarian disease, ovarian quiescence, and ovulation failure often occur concurrently in cows. We have demonstrated that lipopolysaccharides (LPS) produced by Gram-negative bacteria suppress the function of granulosa cells in follicles, leading to ovarian dysfunction in cows.
It is our firm belief that further investigation for this mechanism are needed to enhance reproductive performance and support veterinarians on farm.