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.

Spinal cord injury is an intractable disease that is often encountered in clinical veterinary medicine. A number of treatments including cytokine administration and cell transplantation have been reported, but thus far, effective treatment has not yet been establishd. I am studing the mechanisms of neural regeneration by cytokine administration and neural conversion using small molecule to develop novel thrapy for canine spinal cord injury.

Hypercoagulability disorders, including disseminated intravascular coagulation (DIC) and thrombosis, are common and significantly associated with poor prognosis in dogs with malignant tumors. However, the pathogenesis of DIC is not fully elucidated, as well as available tools for the diagnosis and treatment methods for procoagulant states in the dogs are limited. Currently, I am conducting experiments with the aim of the research to elucidate the pathogenesis of DIC and to develop a novel strategy for diagnosis and treatment of DIC in the dogs.
Also, I am conducting exploration of novel drugs to treat malignancy. Even though a lot of cancer research have been conducted, malignancy is the leading cause of death in humans and dogs. Therefore, malignant tumor is one of the most important desease to be overcomed. Development of the novel strategies for treating malignant tumors is a substantial contribution not only in veterinary medicine but also in human medicine.

Breast tumor cells have various differentiation states, and it has been reported that clinical malignancy and prognosis vary depending on the differentiation stage. Therefore, it is very important to know the differentiation status of mammary tumors, but the mechanisms of tumor differentiation are still largely unknown. This research focuses on the function of type Ⅵ collagen in mammary tumor cell differentiation, mainly using canine mammary tumors. Many canine mammary gland tumors have luminal epithelial progenitor cell characteristics, and it is considered important to understand the differentiation mechanism of this characteristic. I am currently conducting histological and molecular biological research on the differentiation mechanism of breast tumors and related tissue morphology, focusing on various differentiation factors.

My research goal is to identify the impact of antimicrobial use in animals (farm animals & small animals) to the human population using various epidemiological methods, ranging from quantitative to molecular techniques. With the development of the sequencing technology, we will look into the whole-genome of the bacteria and microbiome derived from diverse animals and the environment. My other research interests are in developing epidemiologic data visualization and bacterial evolution analysis.
Image: Showing the prevalence of　antibiotic resistant Salmonella in cattle after the treatment with ceftiofur and chlortetracycline

The α₂-adrenoceptor agonist and opioid analgesic are useful adjunctive drugs for surgical anesthesia due to their potent analgesic properties through acting on neurons intrinsic to the spinal cord, as well as on axon terminals arising from dorsal root ganglia or from descending modulatory pathways. Their combination is known to be potentially beneficial in enhancing analgesic utility via synergistic interaction mainly at the spinal cord mediated by either intercellular or intracellular mechanisms. I am focusing on dexmedetomidine, an α₂-adrenoceptor agonist that its perioperative application is increasingly expanding in human and veterinary medicine in recent years. I am currently conducting research on interactions between dexmedetomidine and opioid on analgesic effects, as well as hemodynamics and fluid homeostasis including renal function and endocrine system, in companion animals.

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.

The bone is essential for structural support of the body and protection of internal organs, and also provides mineral storage for metabolic homeostasis. Bone mass is regulated in a fine-tuned balance between bone formation and resorption, and breakdown of this balance leads to bone disorders characterized by alterd bone mass, such as osteoporosis and osteopetrosis. It has been established that osteoblasts and osteoclasts play critical roles in bone formation and resorption, respectively, and indeed dysfunction of these cells is involved in pathogenesis of alterd bone mass. I have been working on osteoclast. Recently, we reported steoclats specific actin-binding protein Profilin1 knockout (Pfn1-cKO) mice have skeletal dysplasia associated with osteopenia and Pfn1-cKO osteoclasts exhibit increased migration, indicating that Pfn1 protects mice from osteopenia and skeletal deformities by negatively regulating osteoclast migration (Kajikawa S. et al., JBMR PLUS (2018)). Now, I am working on regulatory mechanisms of osteoclast migration by Pfn1.

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.

The number of patients with type 2 diabetes is projected to increase from about 400 million to about 600 million by 2040, and hypertension affects about 1.4 billion people worldwide. It has also been reported that about 85% of type 2 diabetes patients develop hypertension by the age of 50, and about 50% of hypertensive patients develop type 2 diabetes, so there are many patients with both hypertension and diabetes. Functional abnormalities and structural changes in large blood vessels such as the aorta, small blood vessels such as capillaries, and lymphatic vessels are associated with the pathogenesis of hypertension and diabetes. Using genetically engineered animals, excised blood vessels and lymphatic vessels, and cultured cells, I am investigating the pathogenesis of hypertension and diabetes using molecular biological techniques, with the aim of developing new therapeutic agents.

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.

I am working for research on the causes, diagnosis and treatment of dermatosis and ear diseases in companion animals (dogs, cats and exotic pet animals). Furthermore, I am focusing on research on the treatment of infestation by fleas, ticks and Demodex mites. With regard to preventive veterinary medicine, the survey on the prevalence of infectious diseases in dogs and cats and further pharmacoepidemiological studies on vaccines, prophylactics for dirofilariasis, and ectoparasiticides for dogs and cats.

We not only analyze the health status of humans, animals, the environment, and food, but also develop new testing methods to evaluate them.
In recent years, we have been conducting joint research with local governments and companies to develop processing methods to reduce food loss and add value to food ingredients, to evaluate the pharmacokinetics of functional ingredients in foods, and to develop new testing methods for inflammation markers.

Most female mammals have an estrous cycle in which they ovulate periodically. During the estrous cycle, ovarian follicles develop and blood levels of estrogen secreted by the developing follicles increase. This increased estrogen induces ovulation, promotes the proliferation of the endometrium to prepare for implantation of a fertilized egg, and induces sexual behavior by acting on the central nervous system. In addition, estrogen is known to have a wide range of effects, including effects on bone formation, central effects such as memory, and effects on the cardiovascular systems. This means that a wide range of cells are affected by estrogen, and these effects fluctuate during the estrous cycle. In our laboratory, we are investigating the factors and functions affected by estrogen during the estrous cycle, especially in tissues related to reproductive functions such as the pituitary gland and uterus. Oxytocin is a hormone secreted by the posterior pituitary gland and is involved in milk secretion and uterine contractions. Recently, its central effects, such as the ability to trust others more easily, have been attracting attention. Vitamin D is considered to be a hormone and is known to have many actions, just like estrogen. We are currently investigating the regulatory mechanisms of oxytocin receptor and vitamin D receptor expressions, which are involved in the expression of these hormones’ actions.