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Da Hyun Lee

Yonsei University · Biochemistry, Genetics and Molecular Biology

About the Lab

Professor Da Hyun Lee's research lab focuses on the molecular mechanisms underlying liver diseases, particularly nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). The lab investigates key cellular pathways such as the KEAP1-NRF2 antioxidant system, autophagy, and endoplasmic reticulum stress in response to lipotoxicity induced by saturated fatty acids. Current research explores therapeutic strategies targeting the gut-liver axis, including dual GLP-1/GLP-2 receptor agonists, and evaluates natural compounds with cytoprotective and anti-tumor properties. The lab integrates preclinical disease models with molecular and cellular analyses to identify novel targets for metabolic liver disease treatment.

NAFLDNRF2 pathwaylipotoxicityautophagygut-liver axis

Research Overview

Papers
50
Total Citations
1,131
Papers (5y)
13
Primary Field
Biochemistry, Genetics and Molecular Biology

Research Output Trend

Figures are computed from collected data and may differ slightly.

Publications per year (5y)
13total
2022
2023
2024
2025
2026
Citations per year (5y)
116total
20222023202420252026

Selected Papers

15
1
Article|252 citations·2020
SQSTM1/p62 activates NFE2L2/NRF2 via ULK1-mediated autophagic KEAP1 degradation and protects mouse liver from lipotoxicity
Da Hyun Lee, Jeong Su Park, Yu Seol Lee, Jisu Han, Dong‐Kyu Lee, Sung Won Kwon, Dai Hoon Han, Yong‐ho Lee, Soo Han Bae
SJR Q1AutophagyOA

Lipotoxicity, induced by saturated fatty acid (SFA)-mediated cell death, plays an important role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). The KEAP1 (kelch like ECH associated protein 1)-NFE2L2/NRF2 (nuclear factor, erythroid 2 like 2) pathway is a pivotal defense mechanism against lipotoxicity. We previously reported that SQSTM1/p62 has a cytoprotective role against lipotoxicity through activation of the noncanonical KEAP1- NFE2L2 pathway in hepatocytes. However, the unde

Molecular BiologyBiochemistry, Genetics and Molecular Biology
2
Article|91 citations·2016
Ezetimibe, an NPC1L1 inhibitor, is a potent Nrf2 activator that protects mice from diet-induced nonalcoholic steatohepatitis
Da Hyun Lee, Dai Hoon Han, Ki Taek Nam, Jeong Su Park, Soo Hyun Kim, Milim Lee, Gyuri Kim, Byung Soh Min, Bong Soo, Yu Seol Lee, Su Haeng Sung, Haengdueng Jeong
SJR Q1Free Radical Biology and MedicineOA
Molecular BiologyBiochemistry, Genetics and Molecular Biology
3
Article|75 citations·2021
A GLP‐1/GLP‐2 receptor dual agonist to treat NASH: Targeting the gut‐liver axis and microbiome
Eun Ran Kim, Jeong Su Park, Jin Hee Kim, Ji Young Oh, In Jeong Oh, Da Hyun Choi, Yu Seol Lee, Yu seol Lee, I Seul Park, SeungWon Kim, Da Hyun Lee, Jae Hee Cheon
SJR Q1HepatologyOA

BACKGROUND AND AIMS: Currently there is no Food and Drug Administration-approved drug to treat NAFLD and NASH, the rates of which are increasing worldwide. Although NAFLD/NASH are highly complex and heterogeneous conditions, most pharmacotherapy pipelines focus on a single mechanistic target. Considering the importance of the gut-liver axis in their pathogenesis, we investigated the therapeutic effect of a long-acting dual agonist of glucagon-like peptide (GLP)-1 and GLP-2 receptors in mice with

Endocrinology, Diabetes and MetabolismMedicine
4
Article|50 citations·2019
Dual roles of ULK1 (unc-51 like autophagy activating kinase 1) in cytoprotection against lipotoxicity
Jeong Su Park, Da Hyun Lee, Yu Seol Lee, Eunji Oh, Kwang‐Hee Bae, Kyoung‐Jin Oh, Hyun-Mi Kim, Soo Han Bae
SJR Q1AutophagyOA

Saturated fatty acid (SFA)-induced lipotoxicity is caused by the accumulation of reactive oxygen species (ROS), which is associated with damaged mitochondria. Moreover, lipotoxicity is crucial for the progression of nonalcoholic steatohepatitis (NASH). Autophagy is required for the clearance of protein aggregates or damaged mitochondria to maintain cellular metabolic homeostasis. The NFE2L2/NRF2 (nuclear factor, erythroid 2 like 2)-KEAP1 (kelch like ECH associated protein 1) pathway is essential

Molecular BiologyBiochemistry, Genetics and Molecular Biology
5
Article|42 citations·2015
A synthetic chalcone, 2'-hydroxy-2,3,5'-trimethoxychalcone triggers unfolded protein response-mediated apoptosis in breast cancer cells
Da Hyun Lee, You Jung Jung, Dongsoo Koh, Yoongho Lim, Young Han Lee, Soon Young Shin
SJR Q1Cancer Letters
Cell BiologyBiochemistry, Genetics and Molecular Biology
6
Article|41 citations·2016
The natural flavone eupatorin induces cell cycle arrest at the G2/M phase and apoptosis in HeLa cells
Kyung Ho Lee, Da Hyun Lee, You Jung Jung, Soon Young Shin, Young Han Lee
SJR Q2Applied Biological ChemistryOA

Eupatorin (5,3′-dihydroxy-6,7,4′-trimethoxyflavone) is a natural flavone exhibiting antiproliferative activity in diverse cancer cell lines. In the present study, we characterized the cytotoxic effect of eupatorin in HeLa cervical carcinoma cells. Treatment with eupatorin induced cell cycle arrest at the G2/M phase within 12 h, followed by the induction of apoptosis. Eupatorin down-regulated cyclin D1 within 3 h, whereas up-regulated cyclin B1 levels after 12 h. Eupatorin also accumulated p53, p

OncologyMedicine
7
Article|41 citations·2022
PERK prevents hepatic lipotoxicity by activating the p62-ULK1 axis-mediated noncanonical KEAP1-Nrf2 pathway
Da Hyun Lee, Jeong Su Park, Yu Seol Lee, Soo Han Bae
SJR Q1Redox BiologyOA

Hepatic lipotoxicity is a crucial factor in nonalcoholic steatohepatitis resulting from excessive saturated fatty acid-induced reactive oxygen species (ROS)-mediated cell death, which is associated with the accumulation of endoplasmic reticulum (ER) stress in the liver. The unfolded protein response (UPR) alleviates ER stress by restoring ER protein folding homeostasis. However, whether UPR contributes ROS elimination under lipotoxicity remains unclear. The Kelch like ECH-associated protein 1 (K

Molecular BiologyBiochemistry, Genetics and Molecular Biology
8
Article|37 citations·2018
CB1 receptor blockade ameliorates hepatic fat infiltration and inflammation and increases Nrf2-AMPK pathway in a rat model of severely uncontrolled diabetes
Eugene Chang, Dae‐Hee Kim, Hyekyung Yang, Da Hyun Lee, Soo Han Bae, Cheol‐Young Park
SJR Q1PLoS ONEOA

Previous studies have shown that the CB1 receptor antagonist reverses steatohepatitis and its related features of metabolic syndrome, such as obesity and type 2 diabetes. However, the beneficial effects of CB1 receptor blockade on hepatic steatosis and inflammation have not been investigated independently of its effects on body weight and glycemic control. At 32 weeks of age, OLETF rats were administered with rimonabant (10 mg·kg-1·day-1) by oral gavage for 6 weeks. No significant changes in bod

PharmacologyMedicine
9
Article|37 citations·2019
Implantable Vascularized Liver Chip for Cross‐Validation of Disease Treatment with Animal Model
Jung Bok Lee, Jeong Su Park, Young Min Shin, Da Hyun Lee, Jeong‐Kee Yoon, Dae‐Hyun Kim, Ung Hyun Ko, YongTae Kim, Soo Han Bae, Hak‐Joon Sung
SJR Q1Advanced Functional MaterialsOA

Abstract Artificial liver models have been extensively developed for pathological modeling and toxicological studies. However, the prediction of existing in vitro liver models rarely corresponds to what is consequently observed in vivo owing to the structural and functional complexity of the liver. Here, a new liver model designed to enable the implantation and maintenance of liver buds in perfusable 3D hydrogels where a microvascular network develops within a 200 µm diffusion limit is developed

HepatologyMedicine
10
Article|37 citations·2017
The hypertension drug, verapamil, activates Nrf2 by promoting p62-dependent autophagic Keap1 degradation and prevents acetaminophen-induced cytotoxicity
Da Hyun Lee, Jeong Su Park, Yu Seol Lee, Su Haeng Sung, Yong‐ho Lee, Soo Han Bae
SJR Q1BMB ReportsOA

Nuclear factor erythroid 2-related factor 2 (Nrf2) provides a cellular defense against oxidative stress by inducing the expression of antioxidant and detoxification enzymes. The calcium antagonist, verapamil, is an FDA-approved drug prescribed for the treatment of hypertension. Here, we show that verapamil acts as a potent Nrf2 activator without causing cytotoxicity, through degradation of Kelch-like ECH-associated protein 1 (Keap1), a Nrf2 repressor. Furthermore, verapamilinduced Keap1 degradat

Molecular BiologyBiochemistry, Genetics and Molecular Biology
11
Article|36 citations·2015
Concerted action of p62 and Nrf2 protects cells from palmitic acid-induced lipotoxicity
Jeong Su Park, Dong Hoon Kang, Da Hyun Lee, Soo Han Bae
SJR Q2Biochemical and Biophysical Research CommunicationsOA
Molecular BiologyBiochemistry, Genetics and Molecular Biology
12
Article|34 citations·2017
C-C motif chemokine receptor 1 (CCR1) is a target of the EGF-AKT-mTOR-STAT3 signaling axis in breast cancer cells
Soon Young Shin, Da Hyun Lee, Ji Shin Lee, Chan Choi, Jiyoung Kim, Jeong‐Seok Nam, Yoongho Lim, Young Han Lee
SJR Q2OncotargetOA

// Soon Young Shin 1, 2 , Da Hyun Lee 1 , Jishin Lee 3 , Chan Choi 3 , Ji-Young Kim 4 , Jeong-Seok Nam 5 , Yoongho Lim 6 and Young Han Lee 1, 2 1 Department of Biological Sciences, Sanghuh College of Life Sciences, Konkuk University, Seoul, Republic of Korea 2 Cancer and Metabolism Institute, Konkuk University, Seoul, Republic of Korea 3 Department of Pathology, Chonnam National University Medical School, Gwangju, Republic of Korea 4 Laboratory Animal Resource Center, Gwangju Institute of Scienc

OncologyMedicine
13
Article|32 citations·2015
Fenofibrate activates Nrf2 through p62-dependent Keap1 degradation
Jeong Su Park, Dong Hoon Kang, Da Hyun Lee, Soo Han Bae
SJR Q2Biochemical and Biophysical Research CommunicationsOA
Molecular BiologyBiochemistry, Genetics and Molecular Biology
14
Article|31 citations·2015
Anti-invasive effect of β-myrcene, a component of the essential oil from Pinus koraiensis cones, in metastatic MDA-MB-231 human breast cancer cells
Jeong‐Ho Lee, Kicheol Lee, Da Hyun Lee, Soon Young Shin, Yeonjoong Yong, Young Han Lee
Journal of the Korean Society for Applied Biological ChemistryOA
Molecular BiologyBiochemistry, Genetics and Molecular Biology
15
Article|21 citations·2018
Downregulation of α-Melanocyte-Stimulating Hormone-Induced Activation of the Pax3-MITF-Tyrosinase Axis by Sorghum Ethanolic Extract in B16F10 Melanoma Cells
Da Hyun Lee, Sung Shin Ahn, Jung-Bong Kim, Yoongho Lim, Young Han Lee, Soon Young Shin
SJR Q1International Journal of Molecular SciencesOA

Ultraviolet irradiation-induced hyperpigmentation of the skin is associated with excessive melanin production in melanocytes. Tyrosinase (TYR) is a key enzyme catalyzing the rate-limiting step in melanogenesis. TYR expression is controlled by microphthalmia-associated transcription factor (MITF) expression. Sorghum is a cereal crop widely used in a variety of foods worldwide. Sorghum contains many bioactive compounds and is beneficial to human health. However, the effects of sorghum in anti-mela

Cell BiologyBiochemistry, Genetics and Molecular Biology

Research Areas

Molecular BiologyOncologyEpidemiologyBiochemistryMaterials ChemistryEndocrinology, Diabetes and Metabolism

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