research
Research Interest
Elucidationof endo-exogenous stimuli-induced pathological alteration contributing to human chronic diseases including cardiovascular diseases, stroke and diabetes
- - Pathogenesis of ischemic stroke; Neuronal dysfunction induced by exo-/endogenous stimuli
- - Dysregulation of endothelial regeneration after xenbiotic exposure
- - Alteration of endothelial progenitor cells in chronic disorders including diabetes mellitus, hypertension, and atherosclerosis
- - Protective mechanism for xenobiotic-induced acute kidney injury
- - Human health effects induced by xenobiotics including hearvy metals
Research Goal
The goal of research in my lab is to characterize the contribution of endogenous/exogenous stimuli to development of human chronic diseases including cardiovascular diseases, stroke and diabetes. My lab also has a great interest in elucidation of the molecular mechanisms of pathological alteration, to suggest potential preventive approaches against these diseases.
Major research areas
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1. Role of endothelial progenitor cells in diabetic cardiovascular complications
- Impaired angiogenesis is a key feature of many cardiovascular complications in diabetes, including in refractory wounds that result in amputation. Recently, several reports have shown that the function of endothelial progenitor cell (EPC), which plays a key role in endothelial regeneration and neovascularization, are impaired in cardiovascular diseases (CVDs) including diabetes, suggesting that EPC dysfunction may be a major contributor for development and progression of CVDs. Both EPC number and function are decreased in diabetic patients. However, the molecular mechanismsm underlying the impaired EPC function in diabetes poorly understood. We have tried to identify the molecular and cellular mechanisms responsible for diabetic EPC dysfunction.
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2. Elucidation of molecular mechanisms for preconditioning-medaited endogenous neuroprotection against ischemic brain damage
- Stroke is the main leading cause of mortality and also the largesst cause of adult disability. Thrombolysis using tissue plasminogen activator is the only FDA approved therapy for acute stroke but only 2-5% of all stroke patients are treated with thrombolytic therapy. An urgent need exists for the development of new therapies. Recent studies suggest that brain exhibit reduced injury after pre-exposure to sub-lethal levels of a noxious stimulus. This endogenous protection known as preconditioning (PC) may serve as a potential therapeutic option. However, the mechanism by which the brain have the ability to protect themselves during ischemia and other noxious stimuli are not well understood. Our logn-term goal is to identify the molecular and cellular mechanisms responsible for preconditioning and then to use these insights to develop new therapies for stroke
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3. Integrated research for stroke risk assessment
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4. Protective mechanism for xenobiotic-induced acute kidney injury
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5. Human health effects induced by xenobiotics including heavy metals
Lab Technique
In vitro study
- -Isolated primary cells: eurons/astrocytes, bone-marrow derived endothelial progenitor cells
- Cell lines: renal tubular epithelial cells (NRK52e), brain endothelial cells (bEND3), macrophages (RAW 264.7)
- Study of molecular alteration of cells:
- -Apoptosis – Caspase activation, change of mitochondria permeability transition ( ), and cytochrome Crelease from mitochondria
- -Cytotoxicity – PI stainig, MTT assay, LDH assay
- -ROS generation – Chemiluminescence, DCF/DHE staining in flow cytometry, detection of NADPH oxidase activity
- -Alteration of intracellular mediators – Cytosolic Ca2+ determination, protein thiol level, ATP level
- -Change in gene/protin expression level – miRNA/mRNA isolation, mRNAarray with raal-time PCR, Western blot
- Examination of functional change in specific cells (tissue):
- -Primary cortical neurons/astrocytes – NMDA-induced cytotoxicity, Oxygen glucose deprivation-in-duced cyto toxicity, ROS generation, Ca signaling, mitochondrial function
- -Isolated blood vessels – Monitoring of blood vessel tone in organ bath systems
- -Endothelial progenitor cells -Matrigel tube formation assay, adhesion assay, and migration
- -Platelets – aggregation, secretion, phosphatidylserine exposure, microparticle generation and pro-coagulant
activity
- Analytical techniques:
- -Flow cytometry, real-time PCR, western blot, UV-spectrophotometry, fluorimetry, fluorescence microscopy
and confocal microscopy
- Determination of anti-inflammatory activity:
- -nitric oxide synthase (NOS) activity, Cyclooxygenase (COX-2) activity
- Gelatin zymography for detection of MMP-2/9 activity
- DNA isolation and genotyping
Journal Club
(Last 5 years)
Matrix Metalloproteninase-2-Mediated Occludin Degradation and Caveolin-1-Mediated Claudin-5 Redistribution Contribute to Blood-Brain Barrier Damage in Early Ischemic Stroke Stage, Neurobiology of Disease, 32(9):3044-3057, 2012, 신영준 발표
Cadmium-Induced Atutophagy in Rat Kidney: An Early Biomarker of Subtoxic Exposure, Toxicological Sciences, 121(1):31-42, 2011, 김은선 발표
Induction of autophagy contributes to the neuroprotection of nicotinamide phosphoribosyltransferase in cerebral ischemic stroke, Autophagy, 8(1):77-87, 2012, 김경아 발표
Autophagy regulates endoplasmic reticulum stress in ischemic preconditioning, Autophagy, 8(3):310-325, 2012, 노아름 발표