The focus of our study is to understand the developmental mechanisms of cancer and autoimmune diseases, and to develop new treatment strategies for these disorders. In clinics, we performed hematopoietic stem cell transplantation for ~100 patients with hematopoietic malignancies. In previous studies, we have identified human hematopoietic stem cell subpopulations, and their downstream lineage-committed hematopoietic progenitors. Recent studies have shown that these stem and progenitor cells are targets of leukemia transformation. We are trying to identify cancer stem cells from various cancer tissues and leukemias in human, and to understand how the hematopoietic stem cell transplantation eventually eradicates cancer stem cells. To this end, we have developed killing antibodies that can specifically target cancer stem cells to apply our findings to the clinic. Hematopoietic stem cells are the source of all human immune systems including the autoreactive immune cells. We are also performing autologous hematopoietic stem cell transplantation in patients with autoimmune disorders and have success in restoring the normal immune reactions.

1. The basic technique to investigate hematopoietic stem cell biology
2. The isolation of leukemic stem cells and the methods to analyze their developmental mechanism
3. The isolation of cancer stem cells and the methods to analyze their developmental mechanism
4. Immune reactions after allogeneic transplantation
5. The developmental mechanism of autoimmune disorders and new treatment strategies for these disorders
6. The severe infections associated with hematopoietic stem cell transplantation

   

1. Brain research with in vitro and in vivo ischemia model to elucidate pathophysiology of brain ischemia and develop novel therapy against stroke
2. Epidemiological study for stroke using a multicenter stroke database: Fukuoka Stroke Registry (FSR)
3. Pathogenesis of inflammatory bowel diseases in Japanese
4. Pathogenesis of intestinal cancer in inflammatory bowel disease
5. Pathophysiology of nonsteroidal anti-inflammatory drug-induced intestinal damage
6. Longstanding prospective cohort study using general population of Hisayama town; The Hisayama study
7. Epidemiological study for the home blood pressure monitoring to prevent cardiovascular disease and dementia
8. Epidemiological study for diabetes; Fukuoka Diabetes Registry (FDR)
9. Epidemiologic study for chronic kidney disease; Fukuoka Kidney Disease Registry (FKR)
10. Elucidating the pathogenesis of chronic kidney disease and establishing novel treatment approach
11. Mechanism of podocyte injury in nephrotic syndrome

1. Analysis of bioinformatics and construction of evidence based medicine in a wide variety of diseases
2. Genetic and functional analyses using immunohistochemical procedures
3. Procedure of image-enhanced endoscopy and analysis of images
4. Molecular biological experiments using cell culture, RT-PCR, quantitative PCR, Western blotting, RNAi, construction of plasmid, etc.
5. Molecular biological and histological analyses in wide variety of disease model animals and genetically modified mice

   

  Our interests are to clarify the pathogenesis of diabetes, endocrine disorders, gastrointestinal and digestive organ disorders and hematopoietic disorders as follows:

1. Integrated omics analysis of tissue samples and clinical big data to clarify the pathogenesis of endocrine diseases and geriatric diseases.
2. Basic and clinical studies to clarify the pathogenesis of obesity and diabetes and diabetic complications.
3. Basic and clinical studies to clarify the pathogenesis of liver diseases, especially acute liver failure and metabolic dysfunction-associated steatohepatitis.
4. Basic and clinical researches of pancreatic cancer and pancreatic neuroendocrine neoplasms.
5. Basic and clinical researches of functional gastrointestinal disorders and inflammatory bowel diseases.
6. Basic and clinical studies to clarify the pathogenesis of hematological malignancies including leukemia, lymphoma, and myeloma.

Molecular biology, molecular pharmacology, developmental biology, genome cohort study, animal disease models, in vitro study including cell culture, gene transfer, reporter assays, confocal microscopy, flow cytometry, cell sorting.

Despite recent advances in medical treatments, the cardiovascular diseases remain the number killer of human being. In view of aging society, there is an urgent need to overcome refractory cardiovascular diseases. Our department focuses on exploring the pathogenesis of cardiovascular diseases such as atherosclerosis, heart failure (HF) and pulmonary hypertension (PH) using physiological, pharmacological, genetical and molecular biological approach. Novel findings on pathological mechanisms would lead us to develop novel therapeutics for cardiovascular diseases. In addition, in order to establish evidence for cardiovascular disease, we conducted several clinical research regarding national database.

1. Pathological mechanisms of atherosclerosis and vascular remodeling
   • Inflammation in atherosclerotic cardiovascular disease
   • Exosomes in vascular calcification
2. Identification of pathological mechanisms and the development of new therapeutics for HF
   • Organella dysfunction in HF
   • Regulatory mechanism of oxidative stress in HF
   • Development of novel therapy for cardiomyopathy by regulating chronic inflammation
   • Development of novel therapy for drug-induced cardiomyopathy
   • Mechanism of skeletal muscle abnormalities in HF
3. Pathogenesis of PH
   • Pathogenesis in development of pulmonary vascular lesions and right sided HF
   • Novel therapy for PH by regulating chronic inflammation
4. Cardiovascular regulation in hypertension and HF
   • Mechanisms of multi-organ network
   • Central cardiovascular control
5. Translational development of novel therapeutic modality
   • Establishment of novel therapeutics and the conduction of researcher-initiated clinical trials
6. Clinical trials for evidence-based medicine
   • Randomized controlled trial of lipid-lowering therapy in patients of coronary heart disease
   • Multicenter registry for chronic thromboembolic PH
   • Creating and analysis of nationwide HF registry for establishment of novel evidence on HF pathophysiology and treatment
   • Development of effective cardiac rehabilitation program for HF patients

   

In the Department of Respiratory Medicine, we classify respiratory diseases caused by various pathologies into neoplastic diseases, diffuse lung diseases such as interstitial pneumonia, bronchial asthma and obstructive lung diseases, and respiratory infections. We are promoting advanced clinical and basic research with the following approaches.

• Clinical trials for development of novel treatment.
• Elucidation of pathogenesis and development of new treatment methods using molecular, biological and immunological techniques.
• Comprehensive single cell/database analysis using patient/microbial specimens.
• Elucidation of pathogenesis using disease mouse model and human airway epithelium model.

The Department of Respiratory Medicine provides guidance on research topics related to respiratory pathology by the entire teaching staff, without any separation of disease groups.

(Oncological lung disease)

• Research on the elucidation of the mechanisms of resistance to molecular-targeted therapies and their overcoming.
• Research on the mechanisms of expression and regulation of immune checkpoint molecules.
• Research into the mechanisms of action of antibody-drug conjugates and factors influencing their efficacy.
• Research into the effects of the tumor microenvironment on the therapeutic efficacy of anticancer drugs.

(Diffuse lung disease)

• Elucidation of the mechanisms of airway epithelial cell differentiation, proliferation and fibroblast removal.
• Elucidation of the pathogenesis of the development of pulmonary hypertension and search for new treatment methods.
• Identification of specific cell populations involved in the development and progression of interstitial pneumonia.

(Bronchial asthma and obstructive pulmonary disease)

• The immune response of airway epithelial cells to viral infection and the search for targets for asthma therapy.
• The study of the effects of the oral commensal microflora on the progression of chronic obstructive pulmonary disease.
• The study of the airway epithelial barrier function to maintain airway homeostasis.
• Research on physical forces and the progression of emphysematous changes during lung extension and contraction.

(Infectious disease)

• Development of systems to predict new mutant strains of novel coronaviruses.
• Development of treatments for novel coronavirus infections unaffected by mutations.

   

Our goal is to reveal the mechanisms of multiple intractable neurological diseases with unknown etiology and establish novel therapeutics for patients living with those diseases. We have identified various molecules that are necessary for neuronal survival or those which damage neurons or glial cells using multiple experimental techniques including cell biology, molecular immunology, and bioinformatics.

We are searching for graduate students who are interested in the research themes listed below and willing to fight against the neurological intractable diseases. If you have any questions, please contact us anytime.

1. Identification of genetic factors for susceptibility and disease progression in multiple sclerosis and neuromyelitis optica and the mechanisms of those genetic factors contributing disease pathogenesis
2. Identification of the amplification mechanisms of glial inflammation through gap junction protein connexins and establishment of treatment against glial inflammation
3. Identification of disease activity markers for dementia
4. Magnetoencephalography (MEG) study to identify pathomechanisms of epilepsy, neurodegenerative diseases, and higher brain dysfunction
5. Analysis of the molecular mechanisms of multiple system atrophy using genetically engineered mice
6. Identification of pathomechanisms of chronic inflammatory demyelinating polyneuropathy
7. Treatment establishment for neuropathic pain through regulation of Plexin pathways

In our laboratory, we investigate interactions between gene and environment in brain development, and analyze the neural mechanisms of emotion recognition of various mental disorders by functional brain imaging and neurophysiological techniques.

1. Gene-environment interactions of neural circuit of psychiatric disorders
2. Neurophysiological studies for schizophrenia, mood disorders and obsessive compulsive disorders
3. Brain imaging studies of schizophrenia, mood disorders and obsessive compulsive disorders

   

Psychosomatic disorders are defined as “a medical condition that is closely related to psychosocial factors in the onset and course of the physical diseases”.

Our department focuses on the basic and clinical researches for clarifing the pathophysiological mechanisms and the treatment of psychosomatic disorders.

1. Research on the mechanism of relation between stress and neuro-endocrine-immune system.
2. Research on the treatment and prognosis relevant to eating disorders.
3. Research on the pathophysiology and the treatment of chronic pain.
4. Development of questionnaire to evaluate stressful conditions.
5. Functional neuroimaging research on the pathophysiological mechanism and the treatment of psychosomatic disorders.

   

The aim of the clinical and epidemiological studies in our department is to evaluate the natural course and prognosis of clinical infectious diseases, including hepatitis viruses, and human-immune deficiency virus.

We also conduct various studies regarding the associations between persistent infections and cancers or lifestyle-related diseases (diabetes, dyslipidemia, and hypertension), and reactivation of hepatitis B virus.

1. Planning and conduction of clinical study
2. Laboratory work for diagnosis of infectious diseases
3. Learning of molecular technique for infectious diseases
4. Learning of statistical analysis

   

Our research interests are classified into diagnostic imaging and minimally invasive therapy.

The ultimate purpose of diagnostic imaging is to obtain clinically useful biological information from the non-invasive imaging modalities such as CT, MRI and nuclear medicine studies (e.g., PET). These modalities are not only based on the morphologic but also functional imaging. In addition, research projects regarding radiogenomics are ongoing. Furthermore, the Molecular Imaging Center challenges to create new PET tracers for the future molecular imaging.

For minimally invasive therapy, we try to develop a novel IVR technique and high-precision radiotherapy. Additionally, several research projects are ongoing to evaluate effectiveness of heavy ion radiotherapy in cooperation with Saga Heavy Ion Medical Accelerator in Tosu (SAGA HIMAT). We aim at providing the best treatment of choice for each patient.

1. Imaging research using CT and MRI
2. Analysis of pathological condition using PET
3. Development of new IVR techniques and devices
4. Study for individualization to improve an effect of radiotherapy

   

Treatment-refractory cancers exhibit unique genetic features at cellular and/or intratumoral levels. Among the cellular-level features, TP53 loss is the hallmark of chemoresistance. For example, AML (acute myeloid leukemia) cells harboring TP53 mutation are resistant to cytotoxic agents, and AML patients with TP53 mutation generally exhibit poor clinical outcomes. Resistance to treatments, including chemotherapy, radiotherapy and immunotherapy, also stems from genetic heterogeneity of cancer cells in a given tumor, so-called “tumor heterogeneity” or “clonal heterogeneity”. Thus, overcoming (or preventing from occurring) both cellular- and intratumoral genetic features is critical for “precision” cancer therapy. Goals of our research are: 1) to identify novel targets for cancer therapy in a genetic background-dependent manner; 2) to identify targets for novel combination therapies that can overcome tumor heterogeneity and 3) to develop diagnostic/preventive methods to detect cancer before it acquires clonal heterogeneity.

1. Molecular and cellular methods relevant for cancer research.
2. CRISPR/Cas9-mediated gene editing to elucidate gene functions in vitro and in vivo.
3. A series of single-cell technologies to dissect tumor heterogeneity.