Laboratory of Tae Jin Lee, Ph.D.

OVERVIEW

Lee laboratory focuses on basic and translational studies on a role of deregulated microRNAs in tumorigenesis and developing a strategy to treat brain tumors using cutting edge RNA-based nanoparticles. Brain tumors are the second-leading cause of cancer-related death with limited options of treatment. Dr. Lee’s research mainly involves novel nanoparticle based on pRNA derived from the DNA packaging motor of bacteriophage Phi29 for successful delivery of therapeutic microRNAs into brain tumors. They developed a new RNA nanoparticle loaded with various siRNA or microRNA by engineering pRNA from phi29, and further modified them to fit for tumor cell recognition, internalization and delivery of cargo RNA molecule. First batch of RNA nanoparticle has shown to successfully penetrate the blood brain barrier and deliver a cargo siRNA of Luciferase reporter gene in mice model system bearing intracranial tumor, provided a proof-of-concept for efficient delivery of therapeutic RNAs for the treatment of brain tumors. When the anti-miR-21 carrying RNA nanoparticles were systemically administered, growth of glioblastoma xenograft in mouse brain was significantly reduced through reactivation of multiple tumor suppressors released from suppression by the elevated miR-21. The series of work was published in peer-reviewed journals, Oncotarget, Methods in Molecular Biology and Molecular Therapy. Dr. Lee also actively participates in several other studies that examined the role of oncogenic or tumor suppressive microRNAs in various type of human cancers, which were published in well-known peer-reviewed journals including Cancer Cell, Proceedings of the National Academy of Sciences (PNAS), Journal of Experimental Medicine, Clinical Cancer Research, and Oncotarget. Dr. Lee has a long-term goal in his research to make a visible impact on the development of reliable strategy for cancer therapy by reprograming deregulated microRNAs in cancer patients by designing novel and innovative RNA nanoparticles that can be applied to future human clinical trials.

 

CURRENT MEMBERSimage of lab work

Tae Jin Lee, Ph.D., Assistant professor
Margaret Yeh, B.S., Research assistant
Christina Cho, Volunteer student research assistant

CONTACT

Email: [email protected]
Phone: 713-500-6380
Administrative: [email protected]

SELECTED PUBLICATIONS

  1. Pi F, Binzel DW, Lee TJ, Li Z, Sun M, Rychahou P, Li H, Haque F, Wang S, Croce CM, Guo B, Evers BM, Guo P., Nat Nanotechnol (2018) 13(1):82-89
  2. Kim Y, Yoo JY, Lee TJ, Liu J, Yu J, Caligiuri MA, Kaur B, Friedman A., Complex role of NK cells in regulation of oncolytic virus-bortezomib therapy. Proc Natl Acad Sci U S A. (2018) 115(19):4927-4932
  3. Jaime-Ramirez AC, Yu JG, Caserta E, Yoo JY, Zhang J, Lee TJ, Hofmeister C, Lee JH, Kumar B, Pan Q, Kumar P, Baiocchi R, Teknos T, Pichiorri F, Kaur B, Old M. Reolysin and Histone Deacetylase Inhibition in the Treatment of Head and Neck Squamous Cell Carcinoma. Molecular Therapy Oncolytics. (2017)
  4. Lee JY, Park JH, Shin DH, Choi HJ, Won HY, Lee TJ, Croce CM, Kong G. LSD1 Triggers Interplay between Demethylation and Dehydroxylation of HIF1α Protein. Oncogene. (2017)
  5. Ahn J, Park YJ, Chen P, Lee TJ, Jeon YJ, Croce CM, Suh S, Hwang S, Kwon WS, Pang MG, Kim CH, Lee SS, Lee K. Comparative expression profiling of testis-enriched genes regulated during the development of testis. PLoS One. (2017) 12(4):e0175787.
  6. Lee TJ, Yoo JY, Shu D, Li H, Zhang J, Yu JG, Jaime-Ramirez AC, Acunzo M, Romano G, Cui R, Sun HL, Luo Z, Old M, Kaur B, Guo P, Croce CM. RNA nanoparticle based targeted therapy for glioblastoma through inhibition of oncogenic miR-21. Molecular Therapy. (2017). (Epub ahead of print)
  7. Sun HL, Cui R, Zhou J, Teng KY, Hsiao YH, Nakanishi K, Fassan M, Luo Z, Shi G, Tili E, Kutay H, Lovat F, Vicentini C, Huang HL, Wang SW, Kim T, Zanesi N, Jeon YJ, Lee TJ, Guh JH, Hung MC, Ghoshal K, Teng CM, Peng Y, Croce CM. ERK Activation Globally Downregulates miRNAs through Phosphorylating Exportin-5. Cancer Cell. (2016) 30(5):723-736.
  8. Yoo JY, Jaime-Ramirez AC, Bolyard C, Dai H, Nallanagulagari T, Wojton J, Hurwitz BS, Relation T, Lee TJ, Lotze MT, Yu JG, Zhang J, Croce CM, Yu J, Caligiuri MA, Old M, Kaur B. Bortezomib Treatment Sensitizes Oncolytic HSV-1-Treated Tumors to NK Cell Immunotherapy. Clinical Cancer Research. (2016) 22(21):5265-527
  9. Chung S, Lee TJ, Reader BF, Kim JY, Lee YG, Park GY, Karpurapu M, Ballinger MN, Qian F, Rusu L, Chung HY, Unterman TG, Croce CM, Christman JW, FoxO1 regulates allergic asthmatic inflammation through regulating polarization of the macrophage inflammatory phenotype. Oncotarget. (2016). 7(14):17532-46
  10. Cui R, Meng W, Sun HL, Kim T, Ye Z, Fassan M, Jeon YJ, Li B, Vicentini C, Peng Y,Lee TJ, Luo Z, Liu L, Xu D, Tili E, Jin V, Middleton J, Chakravarti A, Lautenschlaeger T, Croce CM., MicroRNA-224 promotes tumor progression in nonsmall cell lung cancer. Proceedings of the National Academy of Sciences U S A. (2015) 112(31):E4288-97.
  11. LeeTJ, Haque F, Vieweger M, Yoo JY, Kaur B, Guo P, Croce CM., Functional assays for specific targeting and delivery of RNA nanoparticles to brain tumor. Methods in Molecular Biology. (2015)1297:137-52.
  12. LeeTJ, Haque F, Shu D, Yoo JY, Li H, Yokel RA, Horbinski C, Kim TH, Kim SH, Kwon CH, Nakano I, Kaur B, Guo P, Croce CM., RNA nanoparticle as a vector for targeted siRNA delivery into glioblastoma mouse model. Oncotarget. (2015) 6(17):14766-76.
  13. Kim T,Cui R, Jeon YJ, Lee JH, Lee JH, Sim H, Park JK, Fadda P, Tili E, Nakanishi H, Huh MI, Kim SH, Cho JH, Sung BH, Peng Y, Lee TJ, Luo Z, Sun HL, Wei H, Alder H, Oh JS, Shim KS, Ko SB, and Croce C. M., Long-range interaction and correlation between MYC enhancer and oncogenic long noncoding RNA CARLo-5. Proceedings of the National Academy of Sciences U S A. (2014) 111(11):4173-8.
  14. Peng Y,Dai Y, Hitchcock C, Yang X, Kassis ES, Liu L, Luo Z, Sun HL, Cui R, Wei H, Kim T, Lee TJ, Jeon YJ, Nuovo GJ, Volinia S, He Q, Yu J, Nana-Sinkam P, and Croce C. M., Insulin growth factor signaling is regulated by microRNA-486, an underexpressed microRNA in lung cancer. Proceedings of the National Academy of Sciences U S A. (2013) 110(37):15043-8.
  15. Suh, S., Yoo, J., Nuovo, G., Jeon, Y., Kim, S., Lee, T., Kim, T., Bakàcs, A., Alder, H, Kaur, B., Aqeilana, R., Pichiorri, F., and Croce, C. M., MicroRNAs/TP53 feedback circuitry in glioblastoma multiforme, Proceedings of the National Academy of Sciences U S A. (2012) 109(14):5316-5321.
  16. Kim, T., Veronese, A., Pichiorri, F., Lee, T., Jeon, Y., Volinia, S., Pineau, P., Marchio, A., Palatini, J., Suh, S., Alder, H., Liu, C., Dejean, A. and Croce C. M., p53 regulates epithelial–mesenchymal transition through microRNAs targeting ZEB1 and ZEB2, Journal of Experimental Medicine (2011) 208(5):875-83.
  17. Lee, T., Zhang, H. Chang, C., Savran C. and Guo, P., Engineering of Fluorescent Energy Conversion Arm of Phi29 DNA Packaging Motor for Single Molecule Studies, Small (2009) 21, 2453-2459.
  18. Wendell, D., Jing, P., Geng, J., Subramarium, V., Lee, T., Montemagno, C. and Guo, P., Double-stranded DNA translocation through a novel phi29 motor-based pore incorporated in lipid membranes, Nature Nanotechnology. (2009) 11, 765-772.
  19. Lee, T., Schwartz, C. and Guo, P., Construction of Bacteriophage Phi29 DNA Packaging Motor and Its Applications in Nanotechnology and Therapy, Annals of Biomedical Engineering. (2009) 10, 2064-2081.
  20. Lee, T., Zhang, H., Liang D. and Guo, P., Strand and nucleotide-dependent ATPase activity of gp16 of bacterial virus phi29 DNA packaging motor, Virology (2008) 380, 69-74.
  21. Guo, P. and Lee, T., Viral nanomotors for packaging of dsDNA and dsRNA, Molecular Microbiology (2007) 64(4), 886–903, Review.
  22. Lee, T. and Guo, P., Interaction of gp16 with pRNA and DNA for genome packaging by the motor of bacterial virus phi29, Journal of Molecular Biology (2006) 356(3):589-599.