초록

고아핵수용체에 의해 발현이 조절되는 각종 대사관련 신규 타깃유전자의 발굴과 함께 고아핵수용체를 제어함으로써 대사관련 유전자의 발현 및 기능 조절에 대한 연구

(출처 : 보고서 요약서 3p)

Abstract ▼

Purpose
Although several drugs for metabolic disease are clinically used, these drugs have limited positive effects and side effects because they are developed without pathological investigation and the detailed molecular mechanism for action. To dissolve these problems, it is required to develop

Purpose
Although several drugs for metabolic disease are clinically used, these drugs have limited positive effects and side effects because they are developed without pathological investigation and the detailed molecular mechanism for action. To dissolve these problems, it is required to develop new drugs based on novel molecular mechanism. Here, we will investigate molecular mechanisms by which nuclear receptor regulates metabolism and provide a key technology for new drug development associated with metabolic liver diseases.

contents
(1) Investigation of regulatory mechanism of glucose and lipid metabolism by nuclear receptor.
▷ Investigation of regulatory mechanism of gluconeogenesis by nuclear receptor: We will identify cellular signaling pathways and transcriptional regulation of nuclear receptor by glucagon or insulin. We will investigate target genes of nuclear receptor and a molecular mechanism by which nuclear receptor regulates hepatic gluconeogenesis.
▷ Investigation of control mechanism of lipid metabolism by nuclear receptor: We will examine cellular signaling pathways and transcriptional regulation of nuclear receptor in ASH (alcoholic steatohepatitis) and NASH (non-alcoholic steatohepatitis). We will analyze target genes of nuclear receptor and a molecular mechanism by which nuclear receptor regulates hepatic lipid metabolism.
▷ Development of new control approaches of target genes using ligand of nuclear receptor: We will confirm the regulatory mechanism for nuclear receptor-mediated target gene expression by its ligand. We will also validate whether the regulation of nuclear receptor by its ligand could ameliorate metabolic liver diseases.
(2) Functional analysis of nuclear receptor and establishment of control technique of its target genes in animal models.
▷ Investigation of the role of nuclear receptor and validation of ligand's function for downstream target genes of nuclear receptor: We will analyze the expression of metabolic disease-related genes and nuclear receptor in animal models, and investigate the possibility to ameliorate diabetes and fatty liver by treatment of ligand in vivo.
▷ Analysis of the pathophysiological role of nuclear receptor in liver metabolism using genetic mutants: We will confirm the susceptibility of nuclear receptor liver-specific transgenic and knockout mice to insulin resistance and fatty liver and identify the possibility to improve diabetes and fatty liver via ligand of nuclear receptor in genetic mouse models.

Developement results
We identified new target genes which are regulated by orphan nuclear receptor and elucidated the molecular mechanism of its expression.
We also confirmed that inhibition of the orphan nuclear receptor by inverse agonist or shRNA can control its target gene function.

Expected Contribution
(1) This project would contribute to the establishment of new therapy to ameliorate metabolic liver disease and provide academic base in cell biology and medical phamacology fields.
(2) Control of orphan nuclear receptor by its ligand would be a potential therapeutic approach for the treatment of metabolic liver disease and provide a new paradigm for new drug development without side effects.
(3) This project would promote new researches in the field of endocrinology and provide a patent for novel molecular mechanism which is comparable to leading groups in nuclear receptor research fields. It would also provide a dominant position for intellectual property rights in new drug development.

(출처 : SUMMARY 5p)

목차 Contents

• 표지 ... 1
• 제 출 문 ... 2
• 보고서 요약서 ... 3
• 국 문 요 약 문 ... 4
• SUMMARY ... 5
• 목차 ... 6
• 1. 연구개발 목표 및 내용 ... 7
• 가. 최종목표 ... 7
• 나. 단계목표 ... 7
• 다. 당초 목표의 수정·보완(중요 연구변경) 사유 ... 7
• 라. 2단계 연차별 연구목표 및 내용 ... 8
• 2. 연구 추진전략 및 방법 ... 9
• 3. 주요 연구개발결과 ... 12
• 가. 계획대비 달성도 ... 12
• 나. 대표적 연구업적 ... 49
• 다. 현 단계 달성된 연구결과의 세계적 연구 위상 ... 50
• 라. 기타 계획하지 않은 연구성과 ... 53
• 마. 연구역량 향상 정도 ... 53
• 바. 세계적 연구리더로서 연구책임자의 성장 정도 ... 53
• 4. 연구수행에 따른 문제점 및 개선방향 ... 54
• 5. 연구개발성과 현황 ... 55
• 6. 국가과학기술종합정보시스템에 등록한 연구시설·장비 현황 ... 60
• 7. 기타사항 ... 60
• 끝페이지 ... 61