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Department of Molecular Pharmacology

Members

Director Mikiya Miyazato
Laboratory chiefs Kazuki Sasaki, Tomohiro Aoki

Research activity in the Department of Molecular Pharmacology

In the cardiovascular system biologically active substances and metabolic enzymes are important players in maintaining homeostatic balance, the dysregulation of which is associated with cardiovascular diseases. Our research goal is to develop diagnostics and therapeutics for the disorders by genetic and biochemical means.

In the Laboratory of Signal Regulation, we are focused on biologically active peptides, an important class of cell-to-cell signaling molecules in the cardiovascular system. Being produced in vivo from translated proteins, endogenous peptides are virtually free from adverse effects when administered to our body. We have used mass spectrometry to identify novel biologically active peptides, which are subsequently studied to elucidate the potential biological role in health and disease.

Cardiovascular diseases are also associated with defects in cell fate control of human vascular and blood cells, and it is important to discover novel mechanisms and drugs regulating cell fate of these cells. In Laboratory of Drug Action and Metabolism, we found that nuclear peroxisome proliferator-activated receptors as well as G-protein-coupled receptors for vasoactive peptides and prostanoids play important roles in cell fate regulation. Regulators of these receptors and related new regulatory principles can be applied to the control of vascular and blood cells in the pathogenesis of atherosclerosis.

Dyslipidemia is also an important target of this department, which is a major risk factor for atherosclerosis causing coronary and cerebral artery diseases. Laboratory of Molecular Structure and Function aims at the establishment of tailor-made-medicine for hypertriglyceridemia. Hypertriglyceridemia is one of risk factors for cardiovascular disease. Catabolism of plasma triglyceride is mainly regulated by lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL). We established methods for the quantification of LPL and HTGL, and then identified LPL gene mutations in the patients with low LPL levels. Our established quantification methods and catalogue of the LPL gene mutations identified in Japanese promote an early diagnosis of causes leading to hypertriglyceridemia.

Major research subjects

Laboratory of Signal Transduction

  1. Mass spectrometry-based profiling of secretory peptides for bioactive peptide discovery
  2. Peptidomics for studying limited proteolysis

Laboratory of Drug Action and Metabolism

  1. Studies on novel mechanism for cell fate regulation in human vascular and blood cells
  2. Investigation of the novel method for regulation of cardiovascular diseases via prevention of monocyte migration

Laboratory of Molecular Structure and Function

  1. Tailor-made medicine for hypertriglyceridemia through developing an early diagnostic method for identifying genetic mutations
  2. Studies on physiological roles of hepatic triglyceride lipase and its contribution to atherogenic lipoprotein production
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