• 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.

• Podoplanin (PDPN/Aggrus/T1α), a platelet aggregation-inducing mucin-like sialoglycoprotein, is highly expressed in many cancers and normal tissues. A neutralizing monoclonal antibody (mAb; NZ-1) can block the association between podoplanin and C-type lectin-like receptor-2 (CLEC-2) and inhibit podoplanin-induced cancer metastasis, but NZ-1 reacts with podoplanin-expressing normal cells such as lymphatic endothelial cells. Recently, we established a platform to produce cancer-specific mAbs (CasMabs). The newly established LpMab-2 mAb reacted with podoplanin-expressing cancer cells but not with normal cells, as shown by flow cytometry and immunohistochemistry; therefore, LpMab-2 is an anti-podoplanin CasMab that is expected to be useful for molecular targeting therapy against podoplanin-expressing cancers.

We can produce cancer-specific mAbs (CasMabs) against all membranous proteins. CasMabs are expected to be useful for molecular targeting therapy without side effects.

• 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.

• There are serious unmet medical needs in kidney diseases. Since fibrosis is a common terminal pathology of various kidney diseases and closely related to renal failure, anti-fibrotic therapies are plausible strategies for kidney diseases. Kidney fibrosis progresses with the emergence of myofibroblasts which produce extracellular matrix. We demonstrated that myofibroblasts originate from renal interstitial fibroblasts, which produce the erythroid growth factor erythropoietin, and that the transformation is reversible. To elucidate mechanisms of kidney fibrosis, we have established a cell line derived from myofibroblasts of mouse kidneys. It has been demonstrated that epigenetic interventions restore the cells (Replic cells) to their original fibroblastic features.

Replic cells provide useful and precise strategies to identify anti-fibrotic drugs.

• Breast cancer is one of the most common malignancies in women worldwide. Therefore, it is very important to investigate biological features of breast carcinoma in order to improve clinical outcome of the patients. It is well known that estrogens play important roles in the development of human breast carcinomas, and endocrine therapies are frequently used in these patients to block the intratumoral estrogen actions. In the Division of Pathology and Histotechnology, we analyze hormone actions in breast carcinoma by pathological methods as well as various molecular biological techniques.

It will be possible to newly develop diagnostic techniques regarding prediction of prognosis and/or effectiveness of treatment in breast cancer patients.

• Using the infectious SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2), we are evaluating and developing new therapeutic drug candidates as well as evaluating disinfectants. Further analyses such as mechanism of action and resistance may be applicable. Other pathogens, including influenza virus and drug-resistant bacteria, will be examined upon request and discussion. Through joint and collaborative research with domestic and overseas pharmaceutical companies and related companies, we have experience of their clinical application including basic research.

We support development and evaluation of various inhibitors and disinfectants for variants of SARS-CoV-2 as well as wild type.

• 1. pressure sensor (needle, optical fiber, etc.) can be inserted into the lymph node to evaluate the risk of lymph node metastasis and treatment.
• 2. domestic patent obtained

Joint research with a medical device manufacturer to develop a diagnosis and treatment system for lymph node metastasis

• 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.

• 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.

• 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.

• 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.