• All the living organisms generate energy from molecular oxygen to maintain their own lives. Once the concentration of oxygen falls down, life activity gets severely hampered and it could sometimes cause death. Typical examples that are related to local hypoxia are ischemic heart disease, stroke and kidney disease.
• We focus on the function of prolyl hydroxylase (PHD) as a sensor to detect the hypoxia, and we are developing drugs to treat ischemic injury by controlling hypoxia.

Currently, we have several compounds that inhibit the PHD. We want to commercialize in conjunction with pharmaceutical companies in Japan and overseas, advancing our non-clinical studies for clinical development.

• 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.

• 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.

This technology is related to the development of a “response-behavior selective” type gas sensor that can discriminate multiple gases in a single sensor channel. The VO₂(M1) phase shows different response behavior (upward/downward) to gases such as ammonia (NH₃) and hydrogen sulfide (H₂S), enabling highly accurate identification even in gas mixtures. It can be operated at room temperature and is expected to be applied in the healthcare field.

Conventional semiconductor gas sensors rely on “response-intensity selectivity,” making it difficult to distinguish between gases with similar properties. In addition, detection of multiple gases requires a multi-channel configuration, which poses challenges to device miniaturization and low power consumption. This technology enables multi-gas discrimination with a single channel, achieving high selectivity while minimizing interference.

• We propose a new sensing concept called “response behavior-selectivity,” in which identification is based on the directionality of the gas response (forward/reverse). Theoretical calculations predict the response behavior, which can be controlled by doping elements, which is unique to this technology. Furthermore, flexible sensor chips can be fabricated, making them suitable for wearable devices.

Potential applications include smart diapers that identify defecation and urination, health monitoring by exhalation, and VOC detection. In the future, we will promote development toward practical applications while further downsizing the device and improving the efficiency of signal transmission by linking it with MEMS technology and IoT.

• HIV infection is one of most serious concern in infectious diseases. We will perform anti-HIV assays for unmet medical needs in control of HIV infections with established novel assays. We have developed reverse transcriptase inhibitor that has novel mechanism of inhibition, translocation-inhibition (J Biol Chem, 2009). Dr Kodama participated in the primary screening and development of a new HIV integrase inhibitor, elvitegravir (J Virol 2009), and a unique reverse transcriptase inhibitor, islatravir, which phase III clinical trials by the Merck & Co., Inc. will complete, soon. We have a representative resistant HIV strain-library for anti-HIV screening and several target oriented high through-put screening systems.

We can establish high through-put screening for new targets, so please consult with us individually. We are open to joint development requiring BSL3/P3 experimental facilities and academic guidance including other microorganisms.

• The present invention relates to a technique for differentiating iPS cells into target differentiated cells while suppressing tumorigenesis in the iPS cells.　In use of a statin and a differentiation inducer, iPS cells are differentiated into target differentiated cells, whereby iPS cells can be differentiated into differentiated cells in which tumorigenesis is suppressed.

• Losing cholesterol homeostasis with inborn errors of metabolisms or hepatobiliary diseases makes a change to in vivo cholesterol metabolism profile and causes the emergence of increased metabolites as conjugates in blood and urine. We have developed an LC/ESI-MS/MS method using fragment patterns characteristic of conjugation types for group-specific and comprehensive analysis of conjugated cholesterol metabolites. This method can contribute for an efficient discovery of diagnostic marker candidates toward various diseases.

After availability verification of candidates as diagnostic markers, it will be required screening tests. We have potential to collaborate with company for development of bioassay systems using antibodies or enzymes.