Yonsei University · Medicine
Professor Sungsoon Fang's research lab focuses on nuclear receptor signaling and its role in metabolic regulation, particularly in liver metabolism, lipid homeostasis, and energy balance. The lab investigates transcriptional mechanisms involving nuclear receptors such as RORα, FXR, and PPARγ, as well as coregulators like SHP, SMRT, and p300, in the context of metabolic diseases including nonalcoholic fatty liver disease (NAFLD), obesity, and insulin resistance. Key research directions include chromatin remodeling, post-translational modifications (e.g., acetylation, methylation), and metabolic reprogramming in cancer and liver disease. The lab employs mouse models, transcriptomics, and molecular biology to dissect gene regulatory networks underlying metabolic homeostasis and disease progression.
Figures are computed from collected data and may differ slightly.
The retinoic acid receptor-related orphan receptor-α (RORα) is an important regulator of various biological processes, including cerebellum development, circadian rhythm and cancer. Here, we show that hepatic RORα controls lipid homeostasis by negatively regulating transcriptional activity of peroxisome proliferators-activated receptor-γ (PPARγ) that mediates hepatic lipid metabolism. Liver-specific Rorα-deficient mice develop hepatic steatosis, obesity and insulin resistance when challenged wit
SHP has been implicated as a pleiotropic regulator of diverse biological functions by its ability to inhibit numerous nuclear receptors. Recently, we reported that SHP inhibits transcription of CYP7A1, a key gene in bile acid biosynthesis, by recruiting histone deacetylases (HDACs) and a Swi/Snf-Brm complex. To further delineate the mechanism of this inhibition, we have examined whether methylation of histones is also involved and whether a functional interplay between chromatin-modifying enzyme
The primary bile acid receptor farnesoid X receptor (FXR) maintains lipid and glucose homeostasis by regulating expression of numerous bile acid-responsive genes, including an orphan nuclear receptor and metabolic regulator SHP. Using SHP as a model gene, we studied how FXR activity is regulated by p300 acetylase. FXR interaction with p300 and their recruitment to the SHP promoter and acetylated histone levels at the promoter were increased by FXR agonists in mouse liver and HepG2 cells. In cont
The ligand-dependent competing actions of nuclear receptor (NR)-associated transcriptional corepressor and coactivator complexes allow for the precise regulation of NR-dependent gene expression in response to both temporal and environmental cues. Here we report the mouse model termed silencing mediator of retinoid and thyroid hormone receptors (SMRT)(mRID1) in which targeted disruption of the first receptor interaction domain (RID) of the nuclear corepressor SMRT disrupts interactions with a sub
Serine is a key contributor to the generation of one-carbon units for DNA synthesis during cellular proliferation. In addition, it plays a crucial role in the production of antioxidants that prevent abnormal proliferation and stress in cancer cells. In recent studies, the relationship between cancer metabolism and the serine biosynthesis pathway has been highlighted. In this context, 3-phosphoglycerate dehydrogenase (PHGDH) is notable as a key enzyme that functions as the primary rate-limiting e
Nonalcoholic fatty liver disease (NAFLD) is one of the causes of fatty liver, occurring when fat is accumulated in the liver without alcohol consumption. NAFLD is the most common liver disorder in advanced countries. NAFLD is a spectrum of pathology involving hepatic steatosis with/without inflammation and nonalcoholic steatohepatitis with accumulation of hepatocyte damage and hepatic fibrosis. Recent studies have revealed that NAFLD results in the progression of cryptogenic cirrhosis that leads
Increased incidence of type I and type II diabetes has been prevailed worldwide. Though the pathogenesis of molecular mechanisms remains still unclear, there are solid evidence that disturbed immune homeostasis leads to pancreatic β cell failure. Currently, autoimmunity and uncontrolled inflammatory signaling pathways have been considered the major factors in the pathogenesis of diabetes. Many components of immune system have been reported to implicate pancreatic β cell failure, including helper
Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with inferior outcomes owing to its low treatment response and high invasiveness. Based on abundant cancer-associated fibroblasts (CAFs) and frequent mutation of breast cancer-associated 1 (BRCA1) in TNBC, the characteristics of CAFs in TNBC patients with BRCA1 mutation compared to wild-type were investigated using single-cell analysis. Intriguingly, we observed that characteristics of inflammatory CAFs (iCAFs) were enri
Cancer is heterogeneous among patients, requiring a thorough understanding of molecular subtypes and the establishment of therapeutic strategies based on its behavior. Gastric cancer (GC) is adenocarcinoma with marked heterogeneity leading to different prognoses. As an effort, we previously identified a stem-like subtype, which is prone to metastasis, with the worst prognosis. Here, we propose FNBP1 as a key to high-level cell motility, present only in aggressive GC cells. FNBP1 is also up-regul
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has posed a serious threat to global public health. A novel vaccine made from messenger RNA (mRNA) has been developed and approved for use at an unprecedented pace. However, an increased risk of myocarditis has been reported after BNT162b2 mRNA vaccination due to unknown causes. In this study, we used single-cell RNA sequencing and single-cell T cell receptor sequencing analyses of peripheral blood mononuclear cells (PBMCs
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been the most dangerous threat to public health worldwide for the last few years, which led to the development of the novel mRNA vaccine (BNT162b2). However, BNT162b2 vaccination is known to be associated with myocarditis. Here, as an attempt to determine the pathogenesis of the disease and to develop biomarkers to determine whether subjects likely proceed to myocarditis after vaccination, we conducted a time series analysis of
A series of fexaramine analogs were synthesized and evaluated to develop an intestine-selective/specific FXR partial agonist. Introduction of both a CN substituent at the C-2 in the biphenyl ring and a fluorine at the C-5 in the aniline ring in fexaramine markedly increased FXR agonistic activity. <b>27c</b> showed 53 ± 3% maximum efficacy relative to GW4064 in an FXR agonist assay. A substantial amount of <b>27c</b> was absorbed in the intestine after oral administration in rats, and then it wa
Alterations of bile acid (BA) metabolism in type II diabetes (T2D) have revealed a link between BAs and metabolic homeostasis.The BA receptors farnesoid X receptor (FXR) and G-protein coupled BA receptor 1 (TGR5) both have shown to regulate lipid, glucose, and energy metabolism, rendering them potential therapeutic targets for T2D therapy.Astonishingly, BA signaling is vital as it has known to be a positive factor for beneficial improvements in vertical sleeve gastrectomy surgery, in turn making
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