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.

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.

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.

I aim to understand and evaluate the physical and mental conditions of livestock animals from the viewpoints of physiology and behavior, and to construct a rearing environment in which livestock animals can maximize their potential. In particular, we are conducting research on the effects of temperature on livestock animals and examining ways to supply healthy, safe, and high-quality livestock products to people even under climate change caused by global warming.

I am studying the effects of radiation therapy in veterinary medicine. We are also investigating the possibility of using sensors to detect animal behavior and applying this to clinical practice.

To protect from viruses, animals including humans have acquired various innate immunity. However, viruses have also gotten the abilities to evade the host immune responses in order to efficiently propagate.
In the relation between viruses and host immune responses, I focus on the “programmed cell death”, which is the cell suicide to inhibit the infection to other cells, and “stress granule”, which is recently identified as the new host immune response. In the future, I’d like to investigate emerging infectious disease viruses to elucidate the viral survival-strategy against the host.

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.

Typical gallbladder diseases in dogs include biliary sludge, gallbladder mucocele, and cholelithiasis, but the pathophysiology remains unclear. I am investigating safer treatment methods by clarifying the detailed pathophysiology of canine gallbladder disease.
In addition, the progress of diagnostic imaging technology in veterinary medicine is remarkable, and I am also working on the application of these data to surgical anatomy (vascular anatomy, etc.), and using these, considering a more safer surgical methods.

Veterinary pathology is the study and elucidation of the causes of animal disease and the study of their mechanisms. There are varies of animal diseases that are recognized dependinng on the animal species, the porpose of keeping animals and anatomical and physiological charaters of animal specises.
The researchs currently focusing on:
1) Pathological study of cardiac dilation in meerkat aims to elucidate the cause of cardiac dilation with suspecting a relationship with nutrients deficiency such as vitamin E and selenium.
2) Patholocical study of dermal fungus disease in Shiro-hebi (albino of Japanese rat snake) aims to elucidate the cause of the disease.

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.

Food hygiene is expected to more important due to HACCP and export of meat and marine product.
Pneumonia is a common disease in feedlot, and Mycoplasma bovis may be involved. The bacteria occur such as pneumonia, mastitis, and arthritis. Endocarditis, which causes lesions in the heart, is occasionally observed at slaughterhouses (Fig). The researches of adhesive factors for vaccine development leads to a stable supply of meat product.
Enterohemorrhagic Escherichia coli (EHEC, STEC), Salmonella, Campylobacter,which are known to be food poisoning, are tested at the Meat Inspection Center. The study of food microbiology that have attracted attention in recent years, such as Clostridium perfringens and Listeria monocytogenes, makes to improve food safety.

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.