• We succeeded in generating highly developed cultured C2C12 myotubes by manipulating intracellular Ca2+ transients with electric pulse stimulation (EPS), that are endowed with similar properties to in vivo skeletal muscle in terms of (1) excitation-induced contractile activity as a result of de novo sarcomere formation, (2) higher energy expenditure (as assessed by AMPK activation), and (3) improved insulin responsiveness (as assessed by exofacial myc-GLUT4 translocation assay).

Taking advantage of our “in vitro Exercise Model", our innovation will be an excellent alternative for the animal experimentation that can be applicable for a wide array of skeletal muscle research including drug screen.

• We perform in-vitro or computational researches for development of medical devices. We develop a model of artery or bone to evaluate medical devices. And we apply optimization way for development of medical devices. Our main target is, currently, stent, or catheter.

Our collaboration company can be; medical equipment, device, medical image, MEMS, standardization, medical training, or polymer.

• Using positron emission tomography (PET), we can measure the regional metabolism, perfusion and signal transmission between neurotransmitters and receptors in various organ systems of living humans and animals, such as the brain and heart. Recent technical developments have shown that the mind, or at least some parts of it, can be demonstrated by "imaging".

Our group has had considerable achievements in clinical research on drug effects and side effects, elucidation of underlying mechanism of alternative and complementary therapies, as well as exercise physiology.

• The islet transplantation is the ideal "minimum invasive" cell transplant therapy for the severe diabetic patients who are suffering with controlling the blood glucose levels. In this project, we try to have a cross organization among the advanced technologies in islet transplantation as one of the typical cases. Our chief objective is to construct the center of medical cell-engineering therapy as successful examples in Tohoku University. We are convinced that technical innovation through this project could contribute much more to the activation of medical industry based upon cell therapy.

We have already established effective academic-industrial alliances regarding our several projects including a development of new type of cell-isolation enzyme. However, we are still looking for possible candidates concerning a special device for cell transplantation and medical grade-pathogen free animals.

• Marfan’s syndrome (MF) is a severe, systemic disorder of connective tissue formation. A variety of MFS therapies have been developed, including surgical therapy for aortic root aneurysm and dissection (AAD) that are life-threatening, traditional medical therapies such as β-adrenergic receptor or angiotensin II receptor blockers for slow aortic growth and to decrease the risk of AAD. However these treatments did not prevent tissue destruction in the AAD of MF. To develop preventive strategy for AAD, it will be necessary to identify molecular mechanisms of microfibril formation and an appropriate fibrillin-1 microfibril associated molecule. Recently, ADAMTSL6β, which is a microfibril-associated extracellular matrix protein contributes the regeneration of microfibril by promoting fibrillin-microfibril assembly. We try to develop ADAMTSL6β as a preventive medicine for AAD of MF by regeneration of fibrillin-1 microfibril assembly.

• The development of organic molecules which function as a catalyst has been extensively investigated to achieve selective and efficient transformation of organic molecules. Brønsted acids and bases are commonly employed as the catalyst in synthetic organic chemistry. To aim at their functionalization, axially chiral phosphoric acids and axially chiral guanidine bases have been developed as chiral Brønsted acid and base catalysts, respectively. A variety of optically active compounds has been synthesized through the development of highly stereoselective reactions using these catalysts.

The development of chiral Brønsted acid and base catalysts has been accomplished as recoverable and reusable organocatalysts and highly stereoselective molecular transformations have been established using these catalysts. The present methodology is applicable to process chemistry in preparing medicines and relevant compounds on the basis of the selective and efficient molecular transformations thus developed with reduction of the waste material.

Amyotrophic lateral sclerosis (ALS) is a representative intractable neurodegenerative disease, and the development of effective therapies is desired. A novel phase I trial of intrathecal administration of recombinant HGF protein was conducted at Tohoku University Hospital. Based on the results, a phase II trial (investigator-initiated clinical trial) to confirm efficacy and safety for ALS was conducted and completed at the Tohoku and Osaka University Hospital from 2016 to 2022. Although there was no statistically significant difference in the primary endpoint, additional analyses are currently ongoing. Clinical development of the same formulation for acute spinal cord injury is also underway.

Simultaneous development of a novel intrathecal formulation of recombinant HGF protein, and a medical device (a subcutaneous port with an intrathecal catheter) that enable repeated intrathecal administration for efficient and selective delivery to the central nervous system.

• We developed a novel rat model of ALS model (Nagai M, et al. 2001)
• Intrathecal continuous administration of HGF protein was confirmed to have a slowing effect on progression in this model
• Phase I and II clinical trials have been completed, and the efficacy is currently being verified through additional analysis

We have been working with Kringle Pharma, Inc., Keio University (Prof. Hideyuki Okano and Prof. Masaya Nakamura), and Asahikawa Medical University (Prof. Hiroshi Funakoshi) to develop this drug. Phase I and II clinical trials for ALS have been completed. In addition, a phase III clinical trial for acute spinal cord injury is near completion. Additional collaboration with pharmaceutical companies is planned.

• GNE myopathy, a type of distal myopathy, is a rare disease and a designated intractable disease in which muscles atrophy and degenerate starting from areas distant from the trunk, gradually depriving the body of freedom. Patients with this disease have mutations in the gene for an enzyme called GNE and cannot synthesize sialic acid, including aceneuramic acid. At the Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, a model mouse was created, and preventive effects were obtained through oral administration of aceneuramic acid.
• In response to this, the field of neurology conducted the world's first physician-initiated Phase I clinical trial in 2010-2011, establishing safety. After physician-initiated Phase II/III trials, extension trials, and efficacy confirmation trials, Nobel Pharma obtained manufacturing and marketing approval for the product named Acenobel® in March 2024. In the future, it is expected that the know-how gained from this seed in creating registries and protocols will be utilized to advance the development of treatments targeting other sialic acid supplements, viral vectors, and oxidative stress.