Research
중점연구분야 (Research focuses): 뇌과학 연구 및 뇌질환 치료제 개발 (Scientific & therapeutic approaches to brain diseases)
(1) 뇌염증 분야: 알츠하이머, 파킨슨, 뇌졸중, 다발성경화증, 만성통증 등과 같은 다양한 뇌신경질환의 근본적인 발병기전 연구 및 치료약물/진단법 개발
(1-1) Neuroinflammation: Study of disease mechanisms and development of therapeutics/diagnostics against neurological diseases such as Alzheimer's disease, Parkinson's disease, stroke, multiple sclerosis, or chronic pain.
본 연구실에서는 알츠하이머, 파킨슨 등과 같은 퇴행성뇌질환의 주범으로 생각되는 “글리아세포”와 “뇌염증반응”을 주로 연구하고 있다. 글리아세포는 신경세포의 기능을 도와주는 좋은 역할도 하지만, 과도하게 지속적으로 활성화된 글리아세포는 신경독성을 나타내기도 한다. 이 경우 신경세포 및 조직보호를 목적으로 글리아세포의 활성 및 뇌염증을 제어할 필요가 있고, 이를 위하여 글리아세포가 활성화되는 경로를 정확히 이해해야 한다. 이러한 배경 하에 글리아세포의 활성화 신호전달과 퇴행성뇌질환의 발병기전 규명이 본 연구실의 주요 연구주제이며, 이와 더불어 과도한 글리아세포의 활성을 조절하는 치료약물 개발과 뇌질환의 조기 진단 표지자 발굴이 또 다른 관심사이다.
Our lab is studying glial cells and neuroinflammation, which are thought to be the major causes of neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. In addition to their beneficial roles, glial cells also show neurotoxic activities when chronically over-activated. In this case we need to downregulate the glial activation as well as neuroinflammation in order to protect neural tissues. Therefore, we need to understand the precise pathways whereby glial activation takes place. Over this background our lab's major research subject would be elucidating the signal pathways involved in glial activation, and as a result finding the pathological mechanisms of neurodegenerative diseases. In addition, we are also interested in the development of therapeutic agents to control glial activation and molecular biomarkers to detect brain diseases in the early stage.
(1-2) Glia secretome: Study of glia-secreted proteins. The Gliome Database 1.0
글리아세포는 다양한 단백질을 분비하여 신경세포 및 다른 글리아세포와 신호를 주고받는다. 이러한 글리아세포 유래의 분비단백을 동정하고 이의 특성을 규명하여 신경염증반응 및 글리아세포의 기능 조절이 가능함.
Neuroinflammation is mainly driven by non-neuronal glial cells in the brain. Glia are heterogeneous and multi-functional cells, which mediate many supportive functions for the brain homeostasis. Recently, paradigm shift from the neurocentric to the gliocentric view of the brain has been proposed, and the complexity of the brain has been revealed by the recent studies on the novel functions of glia in the brain homeostasis as well as neuronal functions. Glia (namely, microglia and astrocytes) also participate in neuroinflammation, which is a common component of many brain disorders. Proteins secreted from glial cells execute much of the important functions of glia under neuroinflammatory condition, and they can be a fundamental source for diagnostic biomarkers and therapeutic targets for the neuroinflammatory diseases. Over the last decade, we investigated the role of astrocyte-secreted proteins such as LCN2, L-PGDS, PTX3, and HMGB in CNS health and disease. In particular, a pathological role of LCN2 has been investigated in a variety of animal models of CNS disorders, including stroke, chronic pain, Parkinson’s disease, vascular dementia, multiple sclerosis, etc.
(2) 분자세포생물학 분야: 세포사멸, 세포이동 및 포식작용의 조절기전 연구
(2) Molecular cell biology: Studying the mechanisms of cell death, migration and phagocytosis
세포의 사멸, 이동, 포식작용 등의 다양한 세포현상은 인체질환에서 중요한 역할을 하며 여러 가지 유전자들에 의해 복잡한 기전으로 조절되는데, 이러한 조절기전을 이해하려는 시도로서, 관련된 유전자를 RNAi screen 등의 방법을 통해 무작위로 선별해내고 이들의 기능을 통합적으로 연구한다. 시스템생물학적 기법을 이용하여 다수의 유전자를 대상으로 그 기능 및 상호작용 네트워크를 밝히고자 한다.
Cell behaviors such as cell death, migration, and phagocytosis play important roles in human diseases, and they are regulated by complex mechanisms and a variety of genetic interactions. To understand these regulatory mechanisms, we are employing systems approaches toward their functions by using unbiased methods such as RNAi screening, in an attempt to discover functional interactive networks of multiple genes.
Publications
- Yeast genetic interaction screen of human genes associated with amyotrophic lateral sclerosis: identification of MAP2K5 kinase as a potential drug target. Genome Res. 2017 Sep;27(9):1487-1500.
- Role of the p55-gamma subunit of PI3K in ALK-induced cell migration: RNAi-based selection of cell migration regulators. Cell Adh Migr. 2017 May 4;11(3):205-210.
- RNAi-based functional selection identifies novel cell migration determinants dependent on PI3K and AKT pathways. Nat Commun. 2014 Oct 28;5:5217.