Research

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1. Epigenetic mechanisms underlying transgenerational effects of dietary stress

We investigate how diet-induced obesity leads to metabolic dysregulation in next generations. We reported that F2 females to HFD founders had a reduced bodyweight relative to F2 to CD founders and exhibited an early onset of impaired glucose homeostasis. The changes in females were linked to hepatic ER stress, leading to suppressed insulin signaling. Also, DNA methylation analysis revealed that the Nr1h3 locus was sensitive to HFD at founder germ cells and the alteration was also detected in the liver of F2 female (Park JH et al., 2018, IJO). We continue to work on identification of mechanisms underlying the transgenerational effects (Park JH et al., 2019, Nutr Res). We also investigate how epigenetic gene regulation responses to metabolic changes during cellular changes such as differentiation. For example, we recently showed that DNA hydroxymethylation is involved in adipogenic differentiation (Yoo Y et al., 2017, IJO & Cho M et al., 2020, BBA-MCL). TET2 is required for initiation of adipogenesis by modulating DNA methylation and expression of PPARγ and DDX5. Moreover, nutrients such as vitamin C and metabolites such as fumarate influence adipogenesis by enhancing and inhibiting TET activities, respectively.


2. Identification of functional compounds targeting epigenetic modulators in disease models including cancer

We identify epigenetic patterns specific for diseases as potential biomarkers and search metabolic or functional compounds targeting epigenetic modulators, which can reverse the altered epigenetic patterns as preventive and therapeutic agents. For examples, Oldenlandia diffusa extract promoted cell death of cisplatin-resistant ovarian cancer cells via modulating histone demethylase (KDM1B) and its transcriptional target, DCLRE1B (Lee et al., IJMS, 2019).


3. Nutrigenomics and Personalized nutrition

We identify genetic and epigenetic variations that modulate the susceptibility to incidence of metabolic diseases in response to environmental stimuli. Recently, we investigated the effects of genetic variants of ADORA gene family on the incidence of chronic disorders such as diabetes, dyslipidemia, and osteoarthritis, and how the effects can be modulated by dietary intakes, using KOGES data (Han et al., 2020, Nutrients). In addition, we try to understand function of candidate genes using genomic analysis of multuple mouse models (Chang et al., 2018, Obesity(Lon)).