• Cyclodepsipeptide natural products include optically active hydroxy acids as well as various unnatural amino acids and exhibit a variety of biological activity depending on the peptide sequence, chirality, and selection of the hydroxy acids. Structure-activity relationships of a synthetic library of natural products could give us significant information of not only biologically important moieties but also intact positions in the biologically active small molecules. On the basis of the former information, more potent compounds and/or peptide mimetics can be designed. The latter information can also be important for making a molecular probe that is used for exploration of a target molecule.

We study for combinatorial synthesis of natural product analogues using solid-phase.

• Focusing our reseach interest mostly on the recognition and complexation behavior control of bioplymrs, such as DNA/RNA, proteines and so on. Another topics are reaction control based on molecular recognition phenomena in both ground and electronically excited states, we are pursuing mechanistic and synthetic studies on asymmetric photochemistry with supramolecular biopolymers as chiral reaction fields.

• We propose the biometric monitor and therapeutic apparatus system with telemedicine, especially for the elderly and patients with chronic diseases. This system is consisted of the sensor probes gathering biometric information and daily living activities, the signal processing units with wireless telecommunication with telemedicine center, and the therapeutic operation units with drug delivery into the mouth.

This system is embedded in usual dental prosthesis, such as denture or mouthpiece, so that this system can be installed into the mouth with no sense of discomfort. The system provides the necessary means of health support in an aging society, especially for the elderly who live alone and the hospital inpatients.

• The currently approved fibrynolytic therapy is only alteplase, but the use of it has been limited to 5% of patients with acute cerebral infarction due to possible side effects including hemorrhagic infarction that may be life-threatening. TMS-007 is a novel drug that has both fibrynolytic activity and brain protective effects. The aim of this project is to perform a clinical trial of this drug and to further achieve a commercial-based clinical use. We believe that this drug would contribute significantly in the treatment of acute cerebral infarction.

• Maximal resection and functional preservation, are often conflicting, but are both important factors to improve patient’s quality of life. Pulsed jet system is designed to achieve this goal by removing lesions without impairing small diameter vessels (100 μm - ). Standardization and specialization of surgical procedures is expected to achieve more easily compared to conventional surgical device using pulsed jet system. We have already reported significant increase of tumor removal rate, significant reduction of intraoperative blood loss and operation time in difficult lesions in the vicinity of sella turcica and skull base through expanded transsphenoidal approach. The system can eject small amount ( - 2 μl) of high speed liquid (- 50 m/s) for minimally invasive surgery, such as endoscopic, catheter, and microscopic surgery. The system is now under stage to expand clinical application outside the field of neurosurgery, and we are expecting new collaboration who can deal with increasing safety, effectiveness, differentiation from conventional instruments, accessibility.

• Effective drug delivery to central nervous system is promising as a new therapeutic strategy against various central nervous system disorders. However, it represents a challenge because systemic delivery is always hindered by blood brain barrier, and local delivery cannot be effective because of the restricted distribution. Recently, local drug delivery system that can achieve robust distribution of the infusates by maintaining a pressure gradient at the tip of the infusion catheter during infusion has developed. Although this method is promising, there still exist several problems as loss of infusates by backflow through catheter tract or inconsistent distribution. We recently developed a method to deliver agents with this method under MRI guidance, and now performing clinical trial to treat recurrent gliomas.

Focal central nervous system disorders such as tumor, epilepsy, and parkinson's disease can be the target for application of this technique. Developments of the new catheters and pre-infusional similation systems are on their way. We are searching for effective collaborative research in this field.

• (1) The amount of anticancer drug required to treat one metastatic lymph node is 1/1,000 to 1/10,000 of the systemic dose.
• (2) The drug can be administered into the lymph node under ultrasound guidance.
• (3) An international patent has been filed for the solvent of the administered drug.

1. Treatment and prophylactic therapy of affiliated lymph nodes in head and neck cancer, breast cancer, etc.
2. Pharmaceutical companies aiming to develop drugs by drug repositioning and generics
3. Medical device manufacturers aiming to develop a dosing system

• Eleven strains of recombinant inbred (RI) mice derived from MRL/lpr and C3H/lpr mice were established. This RI is the only one in the world that randomly develops lesions such as nephritis, arthritis, sialadenitis, vasculitis, and production of autoantibodies in each strain. The genomes of the two strains of mice are randomly held in homozygous condition, and the phenotypes of each strain and the effects of administered drugs could be compared based on their genotype maps. It is possible to identify the regions of gene loci involved in the phenotype and drug sensitivity.

Development of diagnostic and therapeutic agents for autoimmune diseases. It can be applied to the elucidation of the mechanism of onset of immunological adverse events caused by immune checkpoint inhibitors and the development of drugs to prevent the onset of such events, and industry-academia collaboration with pharmaceutical companies, test reagent companies, etc. is possible.