Basic Medicine, Molecular and Cellular Biology

Molecular Endocrinology

To Investigate Molecular Mechanisms and Innovate Novel Drug Discovery for Endocrine Disorders/Metabolic Syndrome Based on Basic Nuclear Hormone Receptor Research

Health Sciences Course

  • Master / Doctoral Degree

Faculty

SUGAWARA, AkiraSUGAWARA, Akira
SUGAWARA, Akira

Professor, M.D., Ph.D.

  • TEL

    +81-22-717-8079, 7483

  • Mail

    akiras2i*med.tohoku.ac.jp (Please convert "*" into "@".)

*Concurrent Position

Research Theme

  • Innovation of novel diagnostic tools and medications for resistant hypertension by targeting adrenal aldosterone synthase (CYP11B2) .
  • Elucidation of the etiology and innovation of novel therapeutics for ACTH-dependent Cushing’s syndrome (Cushing’s disease).
  • Elucidation of the etiology and innovation of novel drugs for diabetic nephropathy by targeting specific transcription factors.
Research Keywords:

Nuclear hormone receptor, Aldosterone synthase (CYP11B2), Cushing's disease, Diabetic nephropathy, Resistant hypertension

Technical Keywords:

Epigenetic analysis, Gene regulation analysis, High-throughput screening (HTS), Cre-loxP system, CRISPR-Cas9 system

Laboratory Introduction

Our department has been focusing on the elucidation of the etiology and the innovation of novel diagnostic tools and therapeutics of the metabolic syndrome X and refractory endocrine/metabolic disorders using molecular biology techniques and genetically modified mice. As shown in Figures 1 and 2, we have clarified novel pleiotropic effects of PPARγ, retinoic acid receptor (RAR), and retinoid X receptor (RXR) against hypertension and atherosclerosis. Recently, we are focusing on the following projects. 1) Innovation of novel anti-hypertensive drugs against resistant hypertension by targeting adrenal aldosterone synthase (CYP11B2) using high-throughput screening (HTS). 2) Innovation of novel diagnostic biomarkers for obesity-related hypertension by the identification of novel adipocyte-derived humoral factors. 3) Elucidation of the etiology of diabetic nephropathy by targeting heparin sulfate of glomerular basement membrane. 4) Innovation of novel drugs against diabetic nephropathy by targeting specific transcription factors using HTS. 5) Innovation of novel drugs against Cushing’s disease by targeting pituitary ACTH-secreting cells. 6) Identification of co-factors and post-translational modifications of nuclear hormone receptors by LC/MS/MS. We are eager to feedback our obtained results to the health and welfare of patients. Students and doctors who are interested in our field are very welcome.

Figure 1. Novel pleiotropic effects of PPARγ

Figure 1. Novel pleiotropic effects of PPARγ

Figure 2. Novel effects of retinoid receptors

Figure 2. Novel effects of retinoid receptors

Recent Publications

  • Saito-Hakoda A, et al. Effects of RXR agonists on cell proliferation/apoptosis and ACTH secretion/Pomc expression. PLoS One. 10(12):e0141960, 2015
  • Yokoyama A, et al. Identification of myelin transcription factor 1 (MyT1) as a subunit of the neural cell type-specific lysine-specific demethylase 1 (LSD1) complex. J Biol Chem. 289(26):18152-18162, 2014
  • Matsuda K, et al. Angiotensin II receptor blockers differentially affect CYP11B2 expression in human adrenal H295R cells. Mol Cell Endocrinol. 383(1-2):60-68, 2014
  • Uruno A, et al. All-trans retinoic acid and a novel synthetic retinoid tamibarotene (Am80) differentially regulate CD38 expression in human leukemia HL-60 cells: possible involvement of protein kinase C-delta. J Leukoc Biol. 90(2):235-247, 2011
  • Uruno A, et al. Peroxisome proliferator-activated receptor-{gamma} suppresses CYP11B2 expression and aldosterone production. J Mol Endocrinol. 46(1):37-49, 2011