• Thymic stromal lymphopoietin(TSLP)has been focused as a master switch for allergy. We established a mouse keratinocyte cell line which constitutively and highly produces TSLP. This cell line will be useful to find the inhibitor of TSLP production and to study biochemical features of production and action of TSLP. The inhibitor of TSLP production might be used as an external or an inhalation drug, indicating low probability of causing a decrease in immune competence.

By using this cell line, we expect we can conduct effective collaborative research in medical fields. For examples, the cell line is useful for analysis of TSLP production and functions, development of inhibitors of TSLP production, and detection of immunotoxic compounds.

• Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease characterized by systematic motor neuron degeneration. Approximately 20% cases of familial ALS are caused by mutations in the superoxide dismutase 1 (SOD1) gene. We developed transgenic rats that express a human SOD1 gene with two different ALS-linked mutations (G93A or H46R) showing progressive motor neuron degeneration and paralysis. The larger size of the rat ALS models as compared with existing mouse models will facilitate studies on neuroprotective and neuro-regenerative strategy involving manipulations of cerebrospinal fluid and spinal cord.

Hepatocyte growth factor (HGF) is one of the most potent survival-promoting factors for motor neurons. Continuous intrathecal infusion of human recombinant HGF (hrHGF) attenuated loss of spinal motor neurons, astrocytosis, and microglial activation, leading to prolonged survival in the ALS rats. Safety and toxicology testing of the hrHGF protein in non-human primates should prompt further clinical trials in human ALS patients.

• Using the yeast transcriptional activator Gal4 system, we reconstituted the production of amyloid beta (Aβ), responsible for Alzheimer disease. Aβ production could be monitored by the positive growth in the selection media or by the reporter enzyme (β-Gal). Utilizing familial Alzheimer disease mutants, we established a system to screen for mutations and chemicals that modulate gamma secretase activity and reduce toxic Aβ42.

Our yeast system can be used to screen for chemicals, natural products, food ingredients, genes, and mutations that modulate γ-secretase activity and block Aβ42 production specifically. We hope to conduct collaboration research with a willing company for a practical application of this technology in industry.

• Using the yeast transcriptional activator Gal4 system, we reconstituted the production of amyloid beta (Aβ), responsible for Alzheimer disease. Aβ production could be monitored by the positive growth in the selection media or by the reporter enzyme (β-Gal). Utilizing familial Alzheimer disease mutants, we established a system to screen for mutations and chemicals that modulate gamma secretase activity and reduce toxic Aβ42.

Our yeast system can be used to screen for chemicals, natural products, food ingredients, genes, and mutations that modulate γ-secretase activity and block Aβ42 production specifically. We hope to conduct collaboration research with a willing company for a practical application of this technology in industry.

• Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease characterized by systematic motor neuron degeneration. Approximately 20% cases of familial ALS are caused by mutations in the superoxide dismutase 1 (SOD1) gene. We developed transgenic rats that express a human SOD1 gene with two different ALS-linked mutations (G93A or H46R) showing progressive motor neuron degeneration and paralysis. The larger size of the rat ALS models as compared with existing mouse models will facilitate studies on neuroprotective and neuro-regenerative strategy involving manipulations of cerebrospinal fluid and spinal cord.

Hepatocyte growth factor (HGF) is one of the most potent survival-promoting factors for motor neurons. Continuous intrathecal infusion of human recombinant HGF (hrHGF) attenuated loss of spinal motor neurons, astrocytosis, and microglial activation, leading to prolonged survival in the ALS rats. Safety and toxicology testing of the hrHGF protein in non-human primates should prompt further clinical trials in human ALS patients.

• Strong points
• Anemia is a very prevalent disease. Nevertheless, an effective therapy is yet to be discovered. Erythropoietin is effective only for those with renal dysfunction. We have found that inhibition of an enzyme for epigenetic regulation results in a prominent increase of erythropoiesis, pointing to a new target for anemia therapy. We have also generated a new, cell-based assay system for the enzymatic activity and carried out small molecule screening.
• Collaboration with industry partners
• We are seeking a collaboration to accelerate the development of new anemia drugs based on these findings. Together we will advance the development of the candidate molecules currently identified as well as conduct further screening of larger chemical space for better candidates and/or for drug repositioning.

• 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.

• Angiogenesis, i.e., the formation of new capillaries, takes place under pathophysiological conditions including cancers, ocular neovascular diseases and atherosclerosis. Anti-angiogenic drugs have been developed, and are now in clinical use. However, because of side effects due to the damage to vascular endothelial cells, the development of anti-angiogenic drugs with different modalities is anticipated. We have isolated vasohibin-1 (VASH1) as a novel angiogenesis inhibitor expressed by endothelial cells (ECs), and vasohibin-2 (VASH2) as its homologue having pro-angiogenic activity.

We are planning to develop strategies of VASH1 potentiation and VASH2 inhibition. For VASH1 potentiation, we are planning to use recombinant VASH1 protein or search low molecular weight substances having VASH1 like activity. For VASH2 inhibition, we are succeeded in the development of neutralizing anti-human VASH2 monoclonal antibody.

• Colorectal cancer (CRC) is one of the most common types of cancer worldwide. Surgical resection is the only curative treatment available for primary CRC. We determined the gene expression profiles for ATP binding cassette (ABC) transporters by RNA sequencing in matched colon cancer and normal colon tissue specimens in order to provide insight into the regulatory mechanisms underlying expression of transporters related to colon carcinogenesis. The expression of ABCC3 was repressed by Wnt signaling pathway, suggesting downregulation of ABCC3 might contribute oncogenesis.

Recently, we easily obtain comprehensive data including transcriptome and other omics data. These data are expected to help find a target for drug development, expecting that pharmaceutical industry interpret and extract new knowledge from them.