Molecular Pharmacology (Pharmacology)

Staff List

Summary of Activity

Heart failure is the symptom in which heart dysfunction eventually results in death due to insufficient delivery of oxygen and nutrients to peripheral organs. Pediatric heart failure is an important cause of death of children. Especially overt heart failure in the preweaning period is malignant and fulminant. Surprisingly, however, there are no specific drugs available for them. We are trying to develop novel drugs to enable these children to safely survive the unfortunately long waiting period by cardiac transplantation.

Research Subject

? Development of drugs specific for pediatric heart failure

Outlook for Research

Treatment of pediatric heart failure has been long-standing unmet medical needs as there are no drugs with evidence due to the difficulties in conducting large pediatric clinical trials and low incentive of pharmaceutical companies. Our research from a basic aspect would shed light on solution of this inconvenient fact.

Outlook for Students After Graduation

Students can learn multidisciplinary approach including molecular biology to comparative integrative physiology in our laboratory. This will help them get their future scientific success.

Major Publications

1. Kashihara, T.*, Kawagishi, H.*, Nakada, T., Numaga-Tomita, T., Kadota, S., Wolf, E.E., Du, C.K., Shiba, Y., Morimoto, S., and Yamada, M. (2020) β-Arrestin-Biased AT1 Agonist, TRV027 Causes a Neonatal-Specific Sustained Positive Inotropic Effect without Increasing Heart Rate. JACC: Basic to Translational Science 5: 1057–1069 (*: equal contribution)

2. Kashihara, T., Nakada, T., Kojima, K., Takeshita, T., and Yamada, M. (2017) Angiotensin II activates CaV1.2 Ca²⁺ channels through β-arrestin2 and casein kinase 2 in mouse immature cardiomyocytes. J. Physiol. (Lond.) 595: 4207-4225

3. Zhang, H., Kashihara, T., Nakada, T., Tanaka, S., Ishida, K., Fuseya, S., Kawagishi, H., Kiyosawa, K., Kawamata, M., Yamada, M. (2019) Prostanoid EP4 receptor-mediated augmentation of Ih currents in Aβ dorsal root ganglion neurons underlies neuropathic pain. J Pharmacol Exp Ther 368:50–58

4. Komatsu, M., Nakada, T., Kawagishi, H., Kato, H., Yamada, M. (2018) Increase in phospholamban content in mouse skeletal muscle after denervation. J Muscle Res Cell Motil 39: 163–173

5. Kawagishi, H., Xiong, J. Rovira, I.I., Pan, H., Yan, Y., Fleischmann, B.J., Yamada, M., Finkel, T. (2018) Sonic hedgehog signaling regulates the mammalian cardiac regenerative response. J. Mol. Cell. Cardiol. 123:180-184

6. Nakada, T., Kashihara, T., Komatsu, M., Kojima, K., Takeshita, T. and Yamada, M. (2018) Physical interaction of junctophilin and the CaV1.1C-terminus is crucial for skeletal muscle contraction. Proc. Natl. Acad. Sci. USA 115: 4507–4512

7. Guo, X., Kashihara, T., Nakada, T., Aoyama, T., Yamada, M. (2018) PDGF-induced migration of synthetic vascular smooth muscle cells through c-Src-activated L-type Ca²⁺ channels with full-length CaV1.2 C-terminus. Pflügers Archiv - Eur J Physiol 470: 909-92