Office: Cancer Institute, CI3329 Rm 316
Lab: CI3329, Rm 308
Education and Training
- M.S. Rutgers University (New Brunswick, NJ) (1996 – 1998)
- Ph.D. – Texas A&M University (College Station, TX) (1998 – 2004)
- Post-doctoral training – University of San Diego, Dr. Michael Karin’s Lab (2004 – 2006)
- Postdoctoral training – University of Texas MD Anderson Cancer Center, Dr. Lin Shiaw-Yih’s Lab (2006 – 2008)
- Research Scientist – Institute of Biosciences and Technology in Texas A&M Health Science Center (2008-2012)
Our lab has focused on the novel role of nuclear receptor NR2E3 in liver diseases and cancer. Among 48 human nuclear receptors, the biological roles of NR2E3 remain largely unknown. Our long-term goal is to develop precision medicine for liver disease and cancer based on mechanism-based, gene-oriented epigenetic therapy. Our immediate objectives are to determine the roles of nuclear receptor NR2E3 in the epigenetic alterations that drive the sex-dependent development of liver diseases and cancer and to develop NR2E3 as a prognostic marker and molecular target for precision medicine. Low NR2E3 expressions are strongly correlated with poor clinical outcomes in liver cancer in multiple data sets (see research statement). Surprisingly, our unpublished results showed that the ablation of NR2E3 in mice drives epigenetic reprogramming, increasing liver fibrosis and tumor formation using NR2E3 knockout mice we generated. Around 16 % of FDA-approved drugs target nuclear receptors (NRs), including PPAR, FXR, etc.; we think our NR2E3 research program has high translational application potential.
Secondly, our research has focused on the role of long noncoding RNAs and aryl hydrocarbon receptor (AHR), an environmental sensor and ligand-activated transcription factor, in pancreatitis and pancreatic cancer. Recently, our lab has identified that environmental toxicant activated AHR induced a pro-oncogenic long noncoding RNA MALAT1. The AHR ligands contain microbiome-derived metabolites, phytochemicals, and environmental toxicants. Typically, AHR can be activated or inhibited, depending on ligand type. This feature makes it an attractive selective molecular target. We previously received an impact score of 36 (19%) of R21 related to the AHR project (see attached CV). Overall, these research projects are innovative and impactful, and if time and resources are given, I am confident that the projects will be successful.
- 07/2022 – UAMS COM Startup funds
- College of Medicine Faculty Research Cost Support Award at University of Cincinnati (2019-2020).
“A role of NR2E3 in liver injury and cancer”
- NIEHS P30 ES006096 Center Environmental Genetics Innovator Award (2019-2020). “A role of environmental toxicant-induced long noncoding RNA in pancreatic disease and cancer”
- College of Medicine Innovative Research Grant. (04/2020-05/2021)
“A role of NR2E3 in liver injury and cancer”.
- 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.
- 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. (2020) Biochem Biophys Res Commun. 532(4):563-569. PMID: 32900487; PMCID: PMC7572814. [Cited 4 times in Scopus].
- Khanal T, Leung YK, Wang J, Timchenko N, Ho SM, Kim K. (2019) NR2E3 is a key component in p53 activation by regulating a long noncoding RNA DINO in acute liver injuries. FASEB J. 33(7):8335-8348. PubMed PMID: 30991008.
- Khanal T, Choi K, Leung YK, Wang J, Kim D, Janakiram V, Cho SG, Puga A, Ho SM, Kim K. (2017) Loss of NR2E3 represses AHR by LSD1 reprogramming, is associated with poor prognosis in liver cancer. Sci Rep. 7(1):10662. PubMed Central PMCID: PMC5587550.
- Khanal T, Kim D, Abby J, Choubey D, Kim K. (2015) 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. Toxicology Letters. 2015 Sep 17;237(3):228-36. PMID:26149760.
- Yang WS, Chadalapaka G, Cho SG, Lee SO, Jin UH, Jutrooru I, Leung YK, Ho SM, Safe S, Kim K. (2014) The transcriptional repressor ZBTB4 regulates EZH2 through a microRNA-ZBTB4-Specificity protein signaling axis. Neoplasia 16(12):1059-69. PMID: 25499219.
- Kim K, Jutooru I, Chadalapaka G, Johnson G, Frank J, Burghardt R, Safe S. (2013) HOTAIR is a negative prognostic factor and exhibits pro-oncogenic activity in pancreatic cancer. Oncogene. 28; 32(13):1616-25. PMID: 22614017.
- Kim K, Chadalapaka G, Lee SO, Yamada D, Sastre-Garau X, Defossez PA, Park YY, Lee JS, Safe S. (2012) Identification of oncogenic microRNA-17-92/ZBTB4/specificity protein axis in breast cancer. Oncogene. 23: 31(8):1034-44. PMID: 21765466.
- Park YY*, Kim K*, Kim SB, Hennessy B, Kim SM, Park ES, Lim JY, Li J, Lu Y, Ana Gonzalez-Anguo , Jeong WJ, Mills GB, Safe S, Lee JS. (2012) Reconstruction of nuclear receptor network reveals that NR2E3 is a novel upstream regulator of ESR1 in breast cancer. EMBO Mol Med. 4(1):52-67. * Co-first Author.
- Naugler, W.E., Sakurai, T., Kim, S., Maeda, S., Kim, K., Elsharkwy, A.M. and Karin, M. (2007) Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. Science., 317:121-24. PMID: 17615358.
- Kim, K., Thu, N., Saville, B., Safe, S. (2003). 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., 17: 804-817. PMID: 12576490.
- Kim, K., Barhoumi, R., Burghardt, R. and Safe, S. (2005) Analysis of estrogen receptor α-Sp1 interactions in breast cancer cells by fluorescence resonance energy transfer. Mol. Endocrinol., 19:843-854. PMID: 15637147. [Cited 54 times in Scopus].