Changes in the global environments have increased incidence of infectious diseases. Most of these diseases are zoonoses which are transmitted from animals to humans. It is an urgent task to control and prevent of zoonotic disease outbreaks. However, it is not simple and straightforward, since the natural reservoir animals and the transmission routes of the causative agents are not elucidate in all zoonoses. From a glocal perspective, the objective of this project is to forestalling outbreaks of zoonotic infection on the basis of epidemiological investigations in Shikoku.
Host specificity of infectious agents are interested because the mechanism is different for each infectious agent. Adenoviruses are believed to be co-evolved with their specific hosts, and usually infect one particular or several, closely related host species. However, certain bat　adenoviruses exhibited a broad range of in vitro cell tropism. We try to elucidate its host-range determinants.

For neruvous system to function properly, each component cell must be produced in adequate numbers, placed in the correct position, and correctly networked with each other. Any failure in any of these processes can impair neurological function and cause neurological and psychiatric disorders. Through the generation and analysis of animal models of neurological and psychiatric disorders, I am working to elucidate the pathogenesis of these diseases and to understand the fundamental mechanisms underlying the development of neural tissue, especially the process of neural network formation.

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.

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.

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 many types of chemical compounds in our environment, and some of them have negative effects on our bodies. Cigarette smoking is a risk factor for various diseases such as atherosclerosis, hypertention, COPD, and cancer. However, there are no clear information which chemical compounds in the cigarette smoke have negative effects on our bodies and cause these diseases. I have previously identified unsaturated carbonyl compounds as stable cytotoxic factors in the gas phase of cigarette smoke. The unsaturated carbonyl compounds are also contained in the smoke from combustion of organic materials such as woods, oil, coal. Thus, the unsaturated carbonyl compounds are regarded as environmental pollutants. The purpose of my study is elucidation of the molecular mechanisms for cytotoxicity of environmental pollutants including unsaturated carbonyl compounds.

Infectious livestock diseases, such as highly pathogenic avian influenza recognized as acute infection that cause tremendous damage to the livestock industry. Acute infections develop relatively early and have significant clinical symptoms, making outbreaks easily recognizable. Conversely, chronic infections that decrease livestock productivity, such as enzootic bovine leukosis (BLV) and bovine viral diarrhea (BVD), have become problematic in recent years. Generally, eradication of chronic infections is extremely difficult and requires considerable time and effort.
I want to study the Effect of these diseases on the livestock industry using field cases, and want to research the viable approach of preventing the spread of BLV and BVD. I also study environmentally friendly insect pest-control using natural materials, such as commercially available diatomite product.

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.

Major histocompatibility complex (MHC) molecule is a glycoprotein expressed on cell surface. MHC molecule plays important role for inducing acquired immunity by presenting self or non-self peptides to T cells. it is known that MHC genes encoding MHC molecules are highly polymorphic genes. In human, various report shows these polymorphisms are related with the risk for graft rejection, tumor and development of autoimmune diseases. However, the correlation between MHC polymorphisms and various diseases in small animals such as dog and cat were unclear so far.
I study about the polymorphisms and functions of MHC in animals and relation of MHC with various diseases. Through these studies, I want to incarnate the regenerated medicine with stem cell transplantation in veterinary medicine and the elucidation for mechanisms of development of autoimmune diseases.

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.

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.

In veterinary clinical practice, neoplastic diseases are important which is one of the leading causes of death. Furthermore, it is known that spontaneous tumors in companion animals which share a living environment with humans exhibit many characteristics in common with human tumors, and research on small animal tumor has the possibility to contribute to the medical field. However, biological characteristics of small animal tumor are largely unknown, and biological analyses to clarify the metabolic changes and gene and protein expression characteristic of tumors, as well as research for novel treatments, are under way. My research aims to analyze the biological characteristics of small animal tumors and explore novel therapeutic strategies such as immunotherapy.

Tumors in companion animals (e.g., dogs and cats) have been increased with the advances in veterinary medicine, reaching to the top cause of death. To overcome it, we need to understand their pathology, i.e., why they occur and how they progress. Currently, I am studying the mechanisms of tumor progression in various companion animal cancers, mainly focusing on canine mammary gland tumors or urothelial cancers, with molecular biological methods as well as state-of-art technology like comprehensive genetic analysis (e.g., microarray, RNA-seq, exome analysis, whole genome analysis), single-cell RNA-seq, or spatial transcriptomics. Also, I am working on the development of deep-learning-based artifical intelligence models with my expertise on bioinformatics to help diagnostic radiology.

Veterinary pathology is the study of the causes of animal diseases and the study of their mechanisms. The results revealed by veterinary pathology are returned to clinical practice to help diagnose and treat animal diseases. Although our research targets all kinds of animals other than humans, we also contribute to the human medicine through basic research using laboratory animals.
I have experience in pathological diagnosis in a variety of animals, including companion animals, industrial animals, laboratory animals, wild animals, exotic animals, zoo and aquarium animals, fish, and invertebrates. I aim to identify issues from spontaneous diseases seen in various animals and to conduct research that can be fed back to clinical practice. At the same time, I will develop basic research using experimental pathological methods.

Chronic exposure to psychological stress leads to increased levels of hormones and cytokines, including glucocorticoids, in the blood or brain tissue. These substances may be involved in the pathogenesis of psychiatric disorders such as depression. To study the chronic effects of glucocorticoids on the nervous system, we are creating animal models of depression to identify useful targets for the treatment of depression. Steroid hormones are also known to protect nerve cells (neuroprotection) and I am investigating how this action is altered in the pathogenesis of depression and whether it can be used to develop treatments.

Regenerative medicine is attracting as much attention in the veterinary medicine field as in the human medicine field. Research in the veterinary medicine is also expected to be returned to the human medicine. Severe spinal cord injuries in small animal clinical practice often result in animals that cannot walk or stand on their own even after treatment, and there is a need to develop new treatment for spinal cord injuries. In this laboratory, we are conducting research on the development of spinal cord regeneration therapies using stem cells that can be isolated from living tissue and various cytokines. We are also researching the effectiveness and efficacy of rehabilitation as well as the development of new treatment methods by further elucidating the pathophysiology of spinal cord injury and studying gait analysis of spinal cord injured animals.

Liife expectancy is getting longer in developed countries, which result in progressive increase in the number of elderly individuals. In parallel, the number of patients with neurodegenerative diseases that cannot yet be cured or significantly slowed, such as frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), is increasing. The cytoplasmic aggregation and accumulation of the nuclear protein TAR DNA-binding protein 43 kDa (TDP-43) is a hallmark of FTD and ALS. TDP-43 action in the nucleus is essential for cellular homeostasis, and TDP-43 aggregation in the cytoplasm is toxic to cells. These findings indicate that TDP-43 accumulation in the cytoplasm mediates development of FTD and ALS. Notably, TDP-43 pathology in the affected region spread over brain and spinal cord simlar to prion diseases. However, the mechanism for cell-to-cell spreading of TDP-43 pathology has been unknown. We previously showed that macroautophagy, a cellular degradation system, suppress aggregate-prone TDP-43 accumulation. Thus, we examine whether dysregulation of macroautophagy develops TDP-43 pathology. For cure of neurodegenerative diseases such as FTD and ALS through suppression of TDP-43 pathology, we are working on fundamental reserach.