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Yong Sun LEE

Name
Yong Sun LEE(full-time professor)
Faculty Appointment
(title, department)
Professor, Department of Cancer Biomedical Science

Area of Expertise
non-coding RNAs
E-mail
yslee@ncc.re.kr, lee.yongsun.go@gmail.com
Work Experience
Assistant Professor (tenure track), Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX (01/2009-06/2017)
Research Associate (Dr. Anindya Dutta’ lab), Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA (07/2003-12/2008 )
Research Associate (Dr. Anindya Dutta’ lab), Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (04/2002-07/2003)
Educational Background
03/1995-08/1998
Department of Microbiology, Seoul National University, Seoul, Korea
Advisor: Dr. Deog Su Hwang
(Ph.D. thesis: Interaction of DnaA and IciA Protein with dnaA Gene Promoter from Escherichia coli)

03/1993-02/1995
Department of Microbiology Seoul National University, Seoul, Korea
Advisor: Dr. Deog Su Hwang
(M.S. thesis: Transcriptional Activation of dnaA Gene by IciA Protein)

03/1988-02/1993
Department of Microbiology, Seoul National University, Seoul, Korea
Research Interests (Please place in paragraph form)
My long-term goal is to expand the knowledge of ncRNAs. Particularly, small ncRNAs of “regulatory” function are one of the most important discoveries in recent years and the focus of the current research, as exemplified by two representative classes - miRNAs and siRNAs. These regulatory RNAs are involved in almost all fundamental aspects of biology – cancer, development, proliferation and apoptosis, immune responses, etc. Besides miRNAs and siRNAs, several other types of ncRNAs have also been (and are still being) identified. I have identified two novel types of ncRNAs: tRFs (tRNA-derived RNA Fragments) and nc886 (non-coding RNA 886). At the present time my main focus is on nc886. nc886 is a potent tumor suppressor and immune modulator. It has a significant impact on cell proliferation and plasticity by interacting with several proteins such as PKR (protein kinase R), Dicer, -catenin, etc and by modulating the fundamental pathways in which they are involved. nc886’s expression pattern in diverse types of cancer (so far including esophageal cancer, gastric cancer, liver cancer, and breast cancer) indicates its diagnostic utility in those tumors. Both tRFs and nc886 are highly novel molecules and have a potential to become breakthrough discoveries with future clinical applications.
International Collaboration
- Dr. Xiaoyong Bao at Department of Pediatrics (The role of miRNAs and tRFs in respiratory syncytial virus infection)
- Dr. Bin Gong at Department of Pathology (The role of miRNAs and tRFs in pathogenesis of Rickettsia conorii)
- Dr. Thomas G Ksiazek at Sealy Center for Vaccine Development and Dr. Bin Gong at Department of Pathology (The role of miRNAs and tRFs in BSL4 viruses)
- Dr. Minkyung Yi at Department of Microbiology and Immunology (The role of nc886 in HCV infection)
- Dr. Junji Iwahara at Department of Biochemistry and Molecular Biology (Protein NMR in tissue culture fluids)
- Dr. Robert A. Waterland at Baylor College of Medicine (epigenetic regulation of nc886 and its impact on PKR)
- Dr. Robert G. Roeder at the Rockefeller University (in vitro study on nc886 expression)
- Dr. Suebpong Tanasanvimon and Dr. Milind Javle at MD Anderson Cancer Center (nc886 in cholangiocarcinoma)
- Dr. Hyun-Sung Lee at Baylor College of Medicine (nc886 in esophageal cancer and hepatoma)
- Ju-Seog Lee at MD Anderson Cancer Center (nc886 in esophageal cancer and hepatoma)
- Dr. Inhan Lee at miRcore, MI (miBridge model for miRNA-target interaction)
- Dr. Stacy Horner at Duke University (nc886 and HCV)
- Dr. Thomas Westbrook at Baylor College of Medicine (nc886 in the MYC pathway)
- Dr. Chanvit Leelayuwat at Khon Khan University, Thailand (nc886 in cholangiocarcinoma)
- Dr. Zdenko Herceg at International Agency for Research on Cancer, France (epigenetic regulation of nc886 in cholangiocarcinoma)
- Dr. Amonrat Jumnainsong at Khon Khan University, Thailand (nc886 in Dengue virus infection)
Achievements
A. ARTICLES IN PEER-REVIEWED JOURNALS:
[journal impact factor; # cited as of Oct 31, 2018]

1. Im WR, Lee HS, Lee YS, Lee JS, Jang HJ, Kim SY, Park JL, Lee Y, Kim MS, Lee JM, Kim IH, Jeon SH*, Lee YS* (2020) A regulatory noncoding RNA, nc886, suppresses esophageal cancer by inhibiting the AKT pathway and cell cycle progression. Cells (* co-corresponding authors) [5.656; 0]

2. Kunkeaw N, Lee YS, Im WR, Jang JJ, SongMJ, Yang B, Park JL, Kim SY, Ku Y, Kim Y, Kang S, Jo H, Jeong JH, Lee HS, Lee JS, Kim HP, Johnson BH, Kim IH*, Lee YS* (2019) Mechanism mediated by a noncoding RNA, nc886, in the cytotoxicity of a DNA-reactive compound. Proc. Natl. Acad. Sci. U. S. A. 116(17):8289-8294. doi: 10.1073/pnas.1814510116. Epub 2019 Apr 4 (* co-corresponding authors) [9.504; 0]

3. Ahn JH, Lee HS, Lee JS, Lee YS, Park JL, Kim SY, Hwang JA, Kunkeaw N, Jung SY, Kim TJ, Lee KS, Jeon SH, Lee I, Johnson BH, Choi JH*, Lee YS* (2018) nc886 is induced by TGF-β and suppresses the microRNA pathway in ovarian cancer. Nat Commun 9(1): 1166. doi: 10.1038/s41467-018-03556-7 (* co-corresponding authors) [12.353; 0]

4. Park JL, Lee YS, Song MJ, Hong SH, Ahn JH, Seo E, Shin SP, Lee SJ, Johnson BH, Stampfer MR, Kim HP*, Kim SY*, Lee YS* (2017) Epigenetic regulation of RNA polymerase III transcription in early breast tumorigenesis. Oncogene 36(49): 6793-6804 (* co-corresponding authors) [7.932; 4]

5. Zhou J, Liu S, Chen Y, Fu Y, Silver AJ, Hill MS, Lee I, Lee YS, Bao X (2017) Identification of two novel functional tRNA-derived fragments induced in response to respiratory syncytial virus infection. J Gen Virol 98: 1600-1610 [2.838; 8]

6. Jang HJ, Lee HS, Burt BM, Lee GK, Yoon KA, Park YY, Sohn BH, Kim SB, Kim MS, Lee JM, Joo J, Kim SC, Yun JS, Na KJ, Choi YL, Park JL, Kim SY, Lee YS, Han L, Liang H, Mak D, Burks JK, Zo JI, Sugarbaker DJ, Shim YM, Lee JS (2017) Integrated genomic analysis of recurrence-associated small non-coding RNAs in oesophageal cancer. Gut 66: 215-225 [14.921; 7]

7. Lee EK, Hong SH, Shin S, Lee HS, Lee JS, Park EJ, Choi SS, Min JW, Park D, Hwang JA, Johnson BH, Jeon SH, Kim IH, Lee YS, Lee YS (2016) nc886, a non-coding RNA and suppressor of PKR, exerts an oncogenic function in thyroid cancer. Oncotarget 7(46): 75000-75012 [5.008; 5]

8. Deng J, Ptashkin RN, Chen Y, Cheng Z, Liu G, Phan T, Deng X, Zhou J, Lee I, Lee YS*, Bao X* (2015) Respiratory syncytial virus utilizes a tRNA fragment to suppress antiviral responses through a novel targeting mechanism. Mol Ther 23(10):1622-1629 (* co-corresponding authors) [6.227; 28]

9. Silver MJ, Kessler NJ, Hennig BJ, Dominguez-Salas P, Laritsky E, Baker MS, Coarfa C, Hernandez-Vargas H, Castelino JM, Routledge MN, Gong YY, Herceg Z, Lee YS, Lee K, Moore SE, Fulford AJ, Prentice AM, Waterland RA (2015) Independent genomewide screens identify the tumor suppressor VTRNA2-1 as a human epiallele responsive to periconceptional environment. Genome Biol 16: 118 [10.810; 74]

10. Lee HS, Lee K, Jang HJ, Lee GK, Park JL, Kim SY, Kim SB, Johnson BH, Zo JI, Lee JS*, Lee YS* (2014) Epigenetic silencing of the non-coding RNA nc886 provokes oncogenes during human esophageal tumorigenesis. Oncotarget 5(11): 3472-3481 (* co-corresponding authors) [6.627; 26]

11. Lee KS, Park JL, Lee K, Richardson LE, Johnson BH, Lee HS, Lee JS, Kim SB, Kwon OH, Song KS, Kim YS, Ashktorab H, Smoot DT, Jeon SH*, Kim SY*, Lee YS* (2014) nc886, a non-coding RNA of anti-proliferative role, is suppressed by CpG DNA methylation in human gastric cancer. Oncotarget 5(11): 3944-3955 (* co-corresponding authors) [6.627; 26]

12. Deng J, Ptashkin RN, Wang Q, Liu G, Zhang G, Lee I, Lee YS, Bao X (2014) Human metapneumovirus infection induces significant changes in small noncoding RNA expression in airway epithelial cells. Molecular therapy Nucleic acids 3: e163 [4.512; 10]

13. Gong B*, Lee YS*, Lee I, Shelite TR, Kunkeaw N, Xu G, Lee K, Jeon SH, Johnson BH, Chang Q, Ha T, Mendell NL, Cheng X, Bouyer DH, Boor PJ, Ksiazek TG, Walker DH (2013) Compartmentalized, functional role of angiogenin during spotted fever group rickettsia-induced endothelial barrier dysfunction: evidence of possible mediation by host tRNA-derived small noncoding RNAs. BMC Infect Dis 13: 285 (* co-corresponding authors) [3.025; 17]

14. Zandarashvili L, Sahu D, Lee K, Lee YS, Singh P, Rajarathnam K, Iwahara J (2013) Real-time kinetics of high-mobility group box 1 (HMGB1) oxidation in extracellular fluids studied by in situ protein NMR spectroscopy. J Biol Chem 288(17): 11621-11627 [4.651; 31]

15. Wang Q, Lee I, Ren J, Ajay SS, Lee YS*, Bao X* (2013) Identification and functional characterization of tRNA-derived RNA fragments (tRFs) in respiratory syncytial virus infection. Mol Ther 21(2): 368-379 (* co-corresponding authors) [7.041; 108]

16. Kunkeaw N, Jeon SH, Lee K, Johnson BH, Tanasanvimon S, Javle M, Pairojkul C, Chamgramol Y, Wongfieng W, Gong B, Leelayuwat C, Lee YS (2013) Cell death/proliferation roles for nc886, a non-coding RNA, in the Protein Kinase R pathway in cholangiocarcinoma. Oncogene 32(32): 3722–3731 [7.357; 38] - featured on www.MDLinx.com

17. Jeon SH, Lee K, Lee KS, Kunkeaw N, Johnson BH, Holthauzen LM, Gong B, Leelayuwat C, Lee YS (2012) Characterization of the direct physical interaction of nc886, a cellular non-coding RNA, and PKR. FEBS Lett 586(19): 3477–3484 [3.538; 23]

18. Gong B, Ma L, Liu Y, Gong Q, Shelite T, Bouyer D, Boor PJ, Lee YS, Oberhauser A (2012) Rickettsiae induce microvascular hyperpermeability via phosphorylation of VE-Cadherins: evidence from atomic force microscopy and biochemical studies. PLoS Negl Trop Dis 6(6): e1699 [4.716; 13]

19. Lee K, Kunkeaw N, Jeon SH, Lee I, Johnson BH, Kang GY, Bang JY, Park HS, Leelayuwat C, Lee YS (2011) Precursor miR-886, a novel noncoding RNA repressed in cancer, associates with PKR and modulates its activity. RNA 17(6): 1076-1089 [6.051; 72]

20. Sun D, Lee YS, Malhotra A, Kim HK, Matecic M, Evans C, Jensen RV, Moskaluk CA, Dutta A (2011) miR-99 family of microRNAs suppresses the expression of prostate-specific antigen and prostate cancer cell proliferation. Cancer Res 71(4): 1313-1324 [8.234; 194]

21. Lee YS*, Shibata Y*, Malhotra A, Dutta A (2009) A novel class of small RNAs: tRNA-derived RNA fragments (tRFs). Genes Dev 23(22): 2639-2649
(* co-first authors) [13.623; 540]

22. Lee YS, Dutta A (2007) The tumor suppressor microRNA let-7 represses the HMGA2 oncogene. Genes Dev 21(9): 1025-1030 [15.050; 1184]
- Highlighted in Genes and Dev. Vol. 21, No.9 (Perspectives in this issue “Oncogenic HMGA2: short or small?” page 1005-1009)

23. Jeon Y, Lee KY, Ko MJ, Lee YS, Kang S, Hwang DS (2007) Human TopBP1 participates in cyclin E/CDK2 activation and preinitiation complex assembly during G1/S transition. J Biol Chem 282(20): 14882-14890 [5.808; 37]

24. Kim HK*, Lee YS*, Sivaprasad U, Malhotra A, Dutta A (2006) Muscle-specific microRNA miR-206 promotes muscle differentiation. J Cell Biol 174(5): 677-687
(* co-first authors) [10.951; 698]
- Cover image of J. Cell Biol. Vol. 174, No.5
- Highlighted in J. Cell Biol. Vol. 174, No.5 (News in this issue “miRNAs halt cell cycle” page 608)
- Highlighted in Nature Vol. 443, No.7107 (Research highlights in this issue “Cell Biology: Muscle building made easy” page 4)

25. Lee YS, Kim HK, Chung S, Kim KS, Dutta A (2005) Depletion of human micro-RNA miR-125b reveals that it is critical for the proliferation of differentiated cells but not for the down-regulation of putative targets during differentiation. J Biol Chem 280(17): 16635-16641 [6.355; 409]

26. Lee YS, Jeon Y, Park JH, Hwang DS, Dutta A (2004) Expression of PACT and EIF2C2, implicated in RNAi and microRNA pathways, in various human cell lines. Korean J Biol Sci 8: 213-220 [0.000; 0]

27. Lee YS, Lee J, Kim HK, Kang S, Han JS, Kim JB, Hwang DS (2003) Trigger factor interacts with DnaA protein to stimulate its interaction with DnaA box. Korean J Biol Sci 7: 81-87 [0.000; 0]

28. Jeon Y, Lee YS, Han JS, Kim JB, Hwang DS (2001) Multimerization of phosphorylated and non-phosphorylated ArcA is necessary for the response regulator function of the Arc two-component signal transduction system. J Biol Chem 276(44): 40873-40879 [7.368; 87]

29. Lee YS, Han JS, Jeon Y, Hwang DS (2001) The arc two-component signal transduction system inhibits in vitro Escherichia coli chromosomal initiation. J Biol Chem 276(13): 9917-9923 [7.368; 43]

30. Joe MK, Park SM, Lee YS, Hwang DS, Hong CB (2000) High temperature stress resistance of Escherichia coli induced by a tobacco class I low molecular weight heat-shock protein. Mol Cells 10(5): 519-524 [0.930; 32]

31. Han JS, Park JY, Lee YS, Thony B, Hwang DS (1999) PhoB-dependent transcriptional activation of the iciA gene during starvation for phosphate in Escherichia coli. Mol Gen Genet 262(3): 448-452 [2.766; 27]

32. Han S, Lee YS, Yim J-b, Hwang DS (1998) Purification and cloning of a protein secreted from Lactobacillus acidophilus. Korean J Biol Sci 2: 355-359 [0.000; 0]

33. Lee YS, Lee H, Yim J, Hwang D (1997) The binding of two dimers of IciA protein to the dnaA promoter 1P element enhances the binding of RNA polymerase to the dnaA promoter 1P. Nucleic Acids Res 25(17): 3486-3489 [4.488; 12]

34. Lee YS, Hwang DS (1997) Occlusion of RNA polymerase by oligomerization of DnaA protein over the dnaA promoter of Escherichia coli. J Biol Chem 272(1): 83-88 [7.452; 34]

35. Lee YS, Kim H, Hwang DS (1996) Transcriptional activation of the dnaA gene encoding the initiator for oriC replication by IciA protein, an inhibitor of in vitro oriC replication in Escherichia coli. Mol Microbiol 19(2): 389-396 [5.024; 31]

B. REVIEWS, COMMENTARIES, AND BOOK CHAPTERS:

1. Wu W, Choi EJ, Lee I, Lee YS, Bao X (2020) Non-coding RNAs and their role in Respiratory Syncytial Virus (RSV) and human Metapneumovirus (hMPV) infections Viruses 12(3), 345; doi:10.3390/v12030345 [3.811; 0]

2. Lee YS, Kunkeaw N, Lee YS (2019) Protein kinase R and its cellular regulators in cancer: An active player or a surveillant? Wiley Interdiscip Rev RNA Jun 23:e1558. doi: 10.1002/wrna.1558. [Epub ahead of print] [5.844; 0]

3. Park JL, Lee YS, Kunkeaw N, Kim SY, Kim IH, Lee YS (2017) Epigenetic regulation of noncoding RNA transcription by mammalian RNA polymerase III. Epigenomics 9: 171-187 [4.044; 4]

4. Fu Y, Lee I, Lee YS*, Bao X* (2015) Small non-coding transfer RNA-derived RNA Fragments (tRFs): their biogenesis, function and implication in human diseases. Genomics Inform 13(4): 94-101 [0.119; 17] (* co-corresponding authors)

5. Lee YS (2015) A novel type of non-coding RNA, nc886, implicated in tumor sensing and suppression. Genomics Inform 13(2): 26-30 [0.119; 7]

6. Jeon SH, Johnson BH, Lee YS (2012) A tumor surveillance model: a non-coding RNA senses neoplastic cells and its protein partner signals cell death. Int J Mol Sci 13(10): 13134-13139 [2.600; 11]

7. Comment in The Digest (2009) Tweaking tumors with microRNAs. Hum Gene Ther 20: 794

8. Lee YS, Dutta A (2009) MicroRNAs in cancer. Annu Rev Pathol 4: 199-227 [7.529; 707]

9. Lee YS, Dutta A (2006) MicroRNAs: small but potent oncogenes or tumor suppressors. Curr Opin Investig Drugs 7(6): 560-564 [3.324; 127]