Cardiovascular Research

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Summary of Activity

In Shinshu University, we are the only laboratory which can generate gene-engineered mice. We are developing novel technologies for genome editing (CRISPR/Cas9 method). For developing next-generation model of human diseases, we invented novel genome editing using maternal Cas9, which enables multiple gene modification at one time.
We are studying various diseases (cancer, atherosclerosis, heart failure, diabetes, renal failure, cerebral infarction, liver cirrhosis and pulmonary fibrosis) and have international patents for drug discovery.

Research Subject

• ? Clarification of the mechanism of disease and development of novel therapies using disease model mice and cultured cells
• ? Roles of vasoactive peptides in vascular development, angiogenesis and cancer metastasis
• ? Generation and analysis of gene-engineered mice using CRISPR/Cas9
• ? Regenerative medical research of heart, vasculature and liver

Outlook for Research

Even by the modern medicine, there still do exist incurable diseases. Mission of medical researchers are to elucidate their causes and develop novel therapies. Our gene-engineered mice help us to execute the mission.

Outlook for Students After Graduation

Our PhD students learn various medical research skills in laboratory. After the graduation, they play leading roles as researches in universities and companies.

Major Publications

1. Xian X, Sakurai T, Kamiyoshi A, Ichikawa-Shindo Y, Tanaka M, Koyama T, Kawate H, Yang L, Liu T, Imai A, Zhai L, Hirabayashi K, Dai K, Tanimura K, Liu T, Cui N, Igarashi K, Yamauchi A, Shindo T
Vasoprotective activities of the adorenomedullin-RAMP2 system in endothelial cells
Endocrinology. 158(5):1359-1372. 2017

2. Imai A, Toriyama Y, Iesato Y, Hirabayashi K, Sakurai T, Kamiyoshi A, Ichikawa-Shindo Y, Kawate H, Tanaka M, Liu T, Xian X, Zhai L, Dai K, Tanimura K, Liu T, Cui N, Yamauchi A, Murata T, Shindo T
Adrenomedullin suppresses vascular endothelial growth factor-induced vascular hyperpermeability and Inflammation in retinopathy
Am J Pathol. 187(5):999-1015. 2017

3. Liu T, Kamiyoshi A, Sakurai T, Ichikawa-Shindo Y, Kawate H, Yang L, Tanaka M, Xian X, Imai A, Zhai L, Hirabayashi K, Dai K, Tanimura K, Liu T, Cui N, Igarashi K, Yamauchi A, Shindo T
Endogenous calcitonin gene-related peptide regulates lipid metabolism and energy homeostasis in male mice
Endocrinology. 158(5):1194-1206. 2017

4. Tanaka M, Koyama T, Sakurai T, Kamiyoshi A, Ichikawa-Shindo Y, Kawate H, Liu T, Xian X, Imai A, Zhai L, Hirabayashi K, Owa S, Yamauchi A, Igarashi K, Taniguchi S, Shindo T
The endothelial adrenomedullin-RAMP2 system regulates vascular integrity and suppresses tumour metastasis
Cardiovasc Res. 111(4):398-409. 2016

5. Sakurai T, Kamiyoshi A, Kawate H, Mori C, Watanabe S ,Tanaka M, Uetake R, Sato M , Shindo T
A non-inheritable maternal cas9-based multiple gene editing system in mice
Sci Rep. 6:20011.doi:10.1038/srep20011. 2016

6. Toriyama Y, Iesato Y, Imai A, Sakurai T, Kamiyoshi A, Ichikawa-Shindo Y, Kawate H, Yamauchi A, Igarashi K, Tanaka M, Liu T, Xian X, Zhai L, Owa S, Murata T, Shindo T
Pathophysiological Function of Endogenous Calcitonin Gene-Related Peptide in Ocular Vascular Diseases
Am J Pathol. 185(6):1783-1794. 2015

7. Yamauchi A, Sakurai T, Kamiyoshi A, Ichikawa-Shindo Y, Kawate H, Igarashi K, Toriyama Y, Tanaka M, Liu T, Xian X, Imai A, Zhai L, Owa S, Arai T, Shindo T
Functional differentiation of RAMP2 and RAMP3 in their regulation of vascular system
J Mol Cell Cardiol. 77:73-85. 2014

8. Koyama T, Ochoa-Callejero L, Sakurai T, Kamiyoshi A, Ichikawa-Shindo Y, Iinuma N, Arai T, Yoshizawa T, Iesato Y, Yang Lei, Uetake R, Okimura A, Yamauchi A, Tanaka M, Igarashi K, Toriyama Y, Kawate H, Adams R.H, Kawakami H, Mochizuki N, Martinez A, Shindo T
Vascular endothelial adrenomedullin-RAMP2 system is essential for vascular integrity and organ homeostasis
Circulation. 127(7) 842-53. 2013

9. Yoshizawa T, Sakurai T, Kamiyoshi A, Ichikawa-Shindo Y, Kawate H, Iesato Y, Koyama T, Uetake R, Yang L, Yamauchi A, Tanaka M, Toriyama Y, Igarashi K, Nakada T, Kashihara T, Yamada M, Kawakami H, Nakanishi H, Taguchi R, Nakanishi T, Akazawa H, Shindo T
Novel regulation of cardiac metabolism and homeostasis by the adrenomedullin-RAMP2 system
Hypertension. 61(2) 341-51. 2013

10.Ichikawa-Shindo Y, Sakurai T, Kamiyoshi A, Kawate H, Iinuma N, Yoshizawa T, Koyama T, Fukuchi J, Iimuro S, Moriyama N, Kawakami H, Murata T, Kangawa K, Nagai R, Shindo T
GPCR modulator protein RAMP2 is essential for angiogenesis and vascular integrity.
J Clin Invest. 118(1):29-39. 2008