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BioLab
BioLab
Univ. of Arkansas for Medical Sciences, Lab of Cancer Epitranscriptomics and Therapeutics
김경현 교수
- 등록2025.02.12
- 조회1750
연구실 소개
연구실 홈페이지
Kyounghyun Kim, Ph.D. (김경현)
Assistant Professor, Department of Pharmacology and Toxicology, Univ. of Arkansas for Medical Sciences, AR, USA
Education
1998 – 2004 Ph.D., Molecular Toxicology, Texas A&M University
1995 – 1997 M.S. Cell & Developmental Biology Rutgers Univ (New Brunswick)
1988 – 1993 B.S. Genetic Engineering Hallym University (Chuncheon)
Academic Experience
2022 – present Assistant Professor, University of Arkansas
2022 – present Assistant Professor, University of Arkansas
2013 – 2021 Assistant Professor, University of Cincinnati College of Medicine
2007 – 2012 Research Scientist, Institute of Biosciences and Technology, Houston.
2005 – 2006 Postdoctoral Fellow, University of California San Diego
2005 – 2006 Postdoctoral Fellow, University of California San Diego
아칸소 대학 의과대학 (University of Arkansas for Medical Sciences, UAMS)은 1879년 아칸소주에서 설립되어 주의 유일한 의학 과학 대학의 핵심 기관으로서, 아칸소 내 대부분의 의사 및 연구자를 양성하는 중요한 역할을 수행해 왔습니다. 아칸소 의과대학의 뛰어난 교수진들은 UAMS 메디컬 센터, 아칸소 아동병원, 센트럴 아칸소 재향군인 의료 시스템, UAMS 지역 센터 및 주 전역과 전 세계 환자들에게 의료 서비스를 제공하며 14,000명 이상의 의료 종사자 및 연구자들이 클리닉 및 바이오 클러스터 연구 단지를 형성해 활동하고 있습니다. 또한, 많은 기초과학 교수진들은 UAMS 대학원에도 임용되어 미래 과학자들을 교육하고 있습니다. 그리고 다학제적 협력을 강조하는 활기차고 세계적 수준의 연구 활동을 통해, 의과대학의 연구자들과 임상의들은 의학 발전의 최전선에서 활약하고 있습니다
아칸소 대학 의과대학 위치해 있는 리틀 록(Little Rock)은 아칸소주 주도이며 클린턴 대통령 도서관(Clinton Presidential Library) 아칸소 미술관 및 로빈슨 센터 등의 문화공간이 있으며 피나클 마운틴 주립공원(Pinnacle Mountain State Park,) 아칸소 리버 트레일(Arkansas River Trail), 빅 댐 브리지(Big Dam Bridge) 및 근처 핫스프링 온천 등이 있어 야외 및 레크리에이션 활동이 용이합니다. 주택, 식료품, 교통, 의료비 등이 상대적으로 낮아 생활에 이점이 있으며 여러 다른 주립 및 사립대학들도 위치해 있어 공립 및 사립학교의 교육 수준도 우수합니다.
연구분야
- 1. Role of Nuclear Receptor NR2E3 in Human Diseases and Cancers
Approximately 16% of FDA-approved drugs target nuclear receptors (NRs), including estrogen receptor (ER), androgen receptor (AR), peroxisome proliferator-activated receptor (PPAR), and Farnesoid X receptor (FXR), for the treatment of various diseases and cancers. Our lab focuses on the novel role of NR2E3 in liver disease and cancer, a nuclear receptor whose biological function remains largely unknown among the 48 human NRs.
Our long-term goal is to develop precision medicine for liver disease and cancer through mechanism-based, gene-targeted epigenetic therapy. Specifically, we aim to: (1) Define the role of NR2E3 in epigenetic alterations driving the sex-dependent progression of liver disease and cancer; (2) Establish NR2E3 as a molecular target for precision medicine.
Clinical data show that low NR2E3 expression correlates with poor prognosis in various cancers, including breast and liver cancers, supporting its tumor-suppressive role. Our published findings further demonstrate that NR2E3 ablation in mice impairs p53 activation, a key tumor suppressor, and promotes epigenetic reprogramming and tumorigenesis through enhanced Wnt/β-catenin signaling.
Notably, NR2E3 contains a ligand-binding pocket like other NRs, suggesting it can accommodate small molecules. This raises the possibility of modulating its tumor-suppressive function as a molecular switch. By characterizing NR2E3’s function and identifying suitable ligands, our research program holds translational potential for developing novel therapeutic strategies. Currently, together with NR2E3 knockout mice models, our lab has focused on the roles of NR2E3 in different cell context using single-cell RNA-seq and Visium spatial transcriptomics (10X Genomics). - 2. N6-methyladenosine (m6A) signaling pathway and Nanopore sequencing (Oxford, UK)
N6-methyladenosine (m6A) is the most prevalent RNA modification in eukaryotic messenger RNA (mRNA) and plays a critical role in post-transcriptional gene regulation. This dynamic and reversible modification influences RNA stability, splicing, translation, and degradation, impacting various physiological and pathological processes. Dysregulation of m6A-modifying enzymes—writers (methyltransferases), erasers (demethylases), and readers (binding proteins)—has been implicated in multiple diseases, including metabolic and neurological disorders, immune regulation, cardiovascular diseases and cancers. Given its context-dependent oncogenic or tumor-suppressive functions, targeting the m6A machinery offers promising therapeutic potential. 
Our lab has investigated the crosstalk between m6A signaling and ligand-activated transcription factors, including nuclear receptors. To better understand these interactions, we utilize Nanopore sequencing technology (Oxford, UK), which enables both sequencing and simultaneous detection of modifications, such as methylation. Nanopore sequencing is a next-generation sequencing (NGS) method that reads DNA or RNA in real-time as they pass through a nanopore. This process involves applying an electric field across the nanopore, causing nucleic acids to disrupt the current in a way that allows for the identification of both sequence and modifications. In addition, effects of ubiquitous or most potent environmental toxicants/carcinogens, including arsenic (a toxic metal), dioxins, and polycyclic aromatic hydrocarbons (PAHs) on the m6A signaling activation or inhibition is under investigation. - 3. Development of combinatorial epigenetic targeting therapies in liver and pancreatic cancers.
Liver and pancreatic cancers are among the most difficult to treat and have poor prognoses due to challenges such as late detection (lack of early biomarkers), tumor heterogeneity, drug resistance, immune evasion, a fibrotic tumor microenvironment, and metastasis, all compounded by significant epigenetic reprogramming. Addressing these obstacles remains a major challenge but is essential for improving outcomes. Given the involvement of multiple factors at various stages of cancer development, combination therapies that target multiple pathways are gaining attention, as they may offer more effective treatment compared to monotherapy targeting a single molecule.
Our lab is focused on developing a novel therapeutic strategy that targets key epigenetic reprogramming enzymes, such as EZH2 (Enhancer of Zeste Homolog 2, a histone methyltransferase), in combination with conventional therapies, including chemotherapy, radiation, and immune checkpoint inhibitors (e.g., PD-1 or PD-L1). EZH2 plays a critical role in epigenetic reprogramming and exhibits strong pro-oncogenic activity in liver and pancreatic cancers. To evaluate the potential of this approach, we will use xenograft and syngeneic tumor models.
연구성과
Selected Publications
Leung YK, Lee SG, Wang J, Guruvaiah P, Rusch NJ, Ho SM, Park C, Kim K. The Loss of an Orphan Nuclear Receptor NR2E3 Augments Wnt/β-catenin Signaling via Epigenetic Dysregulation that Enhances Sp1-β catenin-p300 Interactions in Hepatocellular Carcinoma. Adv Sci (Weinh). 2024 Aug;11(29):e2308539. doi: 10.1002/advs.202308539. Epub 2024 May 24. PMID: 38790135; PMCID: PMC11304255.
Kim K. The Role of Endocrine Disruption Chemical-Regulated Aryl Hydrocarbon Receptor Activity in the Pathogenesis of Pancreatic Diseases and Cancer. Int J Mol Sci. 2024 Mar 29;25(7):3818. doi: 10.3390/ijms25073818. PMID: 38612627; PMCID: PMC11012155.
McDermott A, Kim K, Kasper S, Ho SM, Leung YK. The androgen receptor inhibits transcription of GPER1 by preventing Sp1 and Sp3 from binding to the promoters in prostate cancer cells. Oncotarget. 2022 Jan 7;13:46-60. doi: 10.18632/oncotarget.28169. PMID: 35018219; PMCID: PMC8741193.
Lee JE, Cho SG, Ko SG, Ahrmad SA, Puga A, Kim K. Regulation of a long noncoding RNA MALAT1 by aryl hydrocarbon receptor in pancreatic cancer cells and tissues. Biochem Biophys Res Commun. 2020 Nov 19;532(4):563-569. doi: 10.1016/j.bbrc.2020.08.053. Epub 2020 Sep 6. PMID: 32900487; PMCID: PMC7572814.
Khanal T, Leung YK, Jiang W, Timchenko N, Ho SM, Kim K. NR2E3 is a key component in p53 activation by regulating a long noncoding RNA DINO in acute liver injuries. FASEB J. 2019 Jul;33(7):8335-8348. doi: 10.1096/fj.201801881RR. Epub 2019 Apr 16. PMID: 30991008; PMCID: PMC6593879.
Khanal T, Choi K, Leung YK, Wang J, Kim D, Janakiram V, Cho SG, Puga A, Ho SM, Kim K. Loss of NR2E3 represses AHR by LSD1 reprogramming, is associated with poor prognosis in liver cancer. Sci Rep. 2017 Sep 6;7(1):10662. doi: 10.1038/s41598-017-11106-2. PMID: 28878246; PMCID: PMC5587550.
Khanal T, Kim D, Johnson A, Choubey D, Kim K. Deregulation of NR2E3, an orphan nuclear receptor, by benzo(a)pyrene-induced oxidative stress is associated with histone modification status change of the estrogen receptor gene promoter. Toxicol Lett. 2015 Sep 17;237(3):228-36. doi: 10.1016/j.toxlet.2015.06.1708. Epub 2015 Jul 3. PMID: 26149760; PMCID: PMC4524348.
Yang WS, Chadalapaka G, Cho SG, Lee SO, Jin UH, Jutooru I, Choi K, Leung YK, Ho SM, Safe S, Kim K. The transcriptional repressor ZBTB4 regulates EZH2 through a MicroRNA-ZBTB4-specificity protein signaling axis. Neoplasia. 2014 Dec;16(12):1059-69. doi: 10.1016/j.neo.2014.09.011. PMID: 25499219; PMCID: PMC4309261.
Kim K, Jutooru I, Chadalapaka G, Johnson G, Frank J, Burghardt R, Kim S, Safe S. HOTAIR is a negative prognostic factor and exhibits pro-oncogenic activity in pancreatic cancer. Oncogene. 2013 Mar 28;32(13):1616-25. doi: 10.1038/onc.2012.193. Epub 2012 May 21. PMID: 22614017; PMCID: PMC3484248.
Park YY*, Kim K*, Kim SB, Hennessy BT, Kim SM, Park ES, Lim JY, Li J, Lu Y, Gonzalez-Angulo AM, Jeong W, Mills GB, Safe S, Lee JS. Reconstruction of nuclear receptor network reveals that NR2E3 is a novel upstream regulator of ESR1 in breast cancer. EMBO Mol Med. 2012 Jan;4(1):52-67. doi: 10.1002/emmm.201100187. Epub 2011 Dec 15. PMID: 22174013; PMCID: PMC3376834.
Kim K, Chadalapaka G, Pathi SS, Jin UH, Lee JS, Park YY, Cho SG, Chintharlapalli S, Safe S. Induction of the transcriptional repressor ZBTB4 in prostate cancer cells by drug-induced targeting of microRNA-17-92/106b-25 clusters. Mol Cancer Ther. 2012 Sep;11(9):1852-62. doi: 10.1158/1535-7163.MCT-12-0181. Epub 2012 Jun 29. PMID: 22752225; PMCID: PMC3632183.
Kim K, Chadalapaka G, Lee SO, Yamada D, Sastre-Garau X, Defossez PA, Park YY, Lee JS, Safe S. Identification of oncogenic microRNA-17-92/ZBTB4/specificity protein axis in breast cancer. Oncogene. 2012 Feb 23;31(8):1034-44. doi: 10.1038/onc.2011.296. Epub 2011 Jul 18. PMID: 21765466; PMCID: PMC3288192.
Naugler WE, Sakurai T, Kim S, Maeda S, Kim K, Elsharkawy AM, Karin M. Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. Science. 2007 Jul 6;317(5834):121-4. doi: 10.1126/science.1140485. Erratum in: Science. 2009 Dec 4;326(5958):1346. PMID: 17615358.
Safe S, Kim K. Non-classical genomic estrogen receptor (ER)/specificity protein and ER/activating protein-1 signaling pathways. J Mol Endocrinol. 2008 Nov;41(5):263-75. doi: 10.1677/JME-08-0103. Epub 2008 Sep 4. Erratum in: J Mol Endocrinol. 2009 Apr;42(4):359. Kim, Kyoungkim [corrected to Kim, Kyounghyun]. PMID: 18772268; PMCID: PMC2582054.
Kim K, Barhoumi R, Burghardt R, Safe S. Analysis of estrogen receptor alpha-Sp1 interactions in breast cancer cells by fluorescence resonance energy transfer. Mol Endocrinol. 2005 Apr;19(4):843-54. doi: 10.1210/me.2004-0326. Epub 2005 Jan 6. PMID: 15637147.
Kim K, Thu N, Saville B, Safe S. Domains of estrogen receptor alpha (ERalpha) required for ERalpha/Sp1-mediated activation of GC-rich promoters by estrogens and antiestrogens in breast cancer cells. Mol Endocrinol. 2003 May;17(5):804-17. doi: 10.1210/me.2002-0406. Epub 2003 Feb 6. PMID: 12576490.
연구실 구성원
암생물학, 분자생물학 및 독성학에 관심이 있는 박사과정 학생을 모집합니다.
생물학 연관 학과 학사, 석사, 졸업자분들이 지원을 하실 수 있으며 아칸소주 유일의 의대 박사과정통합 프로그램 (Graduate Program in Interdisciplinary Biomedical Sciences)으로서 학비 및 생횔비 ($ 35,000 per year) 지원됩니다. Single cell RNA-seq, spatial transcriptomics (Visium, and Xeniun, 10X genomics), long-read Nanopore sequencing (Oxford, UK)등의 새로운 바이오기술 등을 활용해 현재 효과적인 치료 및 예방 방법이 없는 간/췌장 손상 및 암을 연구하고 있습니다. 새로이 발견된 Nuclear receptor 및 Noncoding RNAs등의 역할을 규명하고 분자약물타겟으로 개발하고자 하는게 목적입니다.
리들락은 아칸소주의 주도이여 아칸소 유일의 의대 및 병원, 아칸소 Veteran 병원, 아칸소 어린이 병원 등과 함께 바이오 단지를 형성하고 있습니다. 학위 취득 후 졸업생 각자 학계나, 미국 내 정부기관, 또는 제약 회사 등에서 일하고 있습니다. 관심있는 분들의 연락을 바랍니다.
Interested individuals should email a CV and a list of three references to Kyounghyun Kim, Ph.D.
Email: kkim@uams.edu
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