• 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.

• McH/lpr-RA1 mice are recombinant congenic mice descended from MRL/lpr and C3H/lpr mice and develop arthritis, vasculitis, and sialadenitis with high frequency and severity, with severe pannus formation similar to rheumatoid arthritis, polyarteritis nodosa, and Sjogren's syndrome. On the other hand, McH/lpr-RA1 mice do not develop systemic lymphadenopathy and severe nephritis as seen in MRL/lpr mice, so they are easy to breed and maintain and can be used for long-term drug administration experiments.

Development of diagnostic and therapeutic agents for collagen 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, etc. Industry-academia collaboration with pharmaceutical companies, test reagent companies, etc. is possible.

• 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.

• Chemotherapy toward bacterial infection, which dates back to the discovery of penicillin, opened up the golden era of antibiotics. Thereafter, various clinically important antibiotics were introduced into the clinic, and hence serious bacterial infectious diseases were eradicated. However, this ephemeral hope has been disappearing due to the emergence of antibiotic resistant pathogens toward every new antibiotics launched into the clinic, such as multidrug-resistant Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA). To combat these life-threatening pathogens, there is a pressing need to develop new antibiotics. However, new antibiotics discovered in the future will be nullified by development of resistance to these antibiotics, since their targets are essential for bacterial survival. From this aspect in which inhibitors of the essential functions inevitably select resistant mutants, bacterial virulence could be a fascinating target for developing new antibiotics, because virulence attenuators are thought to be less likely to generate resistance. We focus on a novel protein translocation system, Tat, since this system appears to be involved in several aspects of bacterial virulence and is not present in mammalian cells, and iron-metabolism-associated system as novel targets for development of their inhibitors. We hope to conduct collaborative research with a willing company for a practical application of this technology in industry.

• Bone marrow stromal cells have great advantages since they are already applied to patients either by auto- or allo-transplantations, can be harvested in large numbers (10 million cells within several weeks) as adherent cells from bone marrow aspirates, and are with low risk of tumorigenesis. Furthermore, marrow bank is available. Likewise, mesenchymal cells harvested from umbilical cord are also easily accessible from cord bank and are a good source of mesenchymal stem cells. We have established a system to induce functional Schwann cells (peripheral glia) from human bone marrow stromal cells and umbilical cord mesenchymal cells by treating cells with a series of reagents and cytokines. This induction system successfully generates Schwann cells with very high efficiency (~97%). They were confirmed to elicit neural regeneration in peripheral nerve damages and spinal cord injury (Eur, J. Neurosci, 2001; J. Neurosurg, 2004, J. Neuropathol. Exp. Neurol, 2005, Biochem Biophys Res Commun, 2007; Tissue Eng., 2011). The efficiency and safety of induced Schwann cells were demonstrated in monkey by 1 year follow up (Exp. Neurol., 2010). Importantly, induced cells not only elicited neural regeneration in both peripheral and central nervous system, but also contributed to functional recovery by restoring myelin and saltatory conduction. Therefore, these cells are expected to be effective to demyelinating diseases as well. We hope to collaborate with companies and research groups who are willing to utilize our system.