Laboratory Introduction - Overview - Seoul National University Cancer Research Institute

Lab of Regulation of Cellular Functions

The "Lab of Regulation of Cellular Functions" was opened at CRI, SNU in 2001 and moved to Department of Pharmacy, SNU in 2009. Currently, we keep studying on a tetraspanin, TM4SF5, with regards to liver disease with purposes of therapeutic development of anti-TM4SF5 small synthetic compound and antibody. The effors involve collaboration with clinical MD and antibody-enginnering partners in other domestic institutes. The liver diseases include nonalcoholic fatty liver, NASH, fibrosis, and HCC. Recently, our research interests become to expand to immuno-metabolism, inflammation, and immunocheck point regulation, in addition to nutrient metabolisms.

Related Researcher

Jung Weon Lee Professor

Email : jwl@snu.ac.kr
Laboratory Homepage

Research topics

We have kept the research interests as followings. 1. Cross-talks between integrin and TGFb signaling pathways. 2. Identification of TM4SF5 gene upon hepatocyte adhesion and relevance to cancer cell behaviors 3. Dynamics and Mechanisms of Cellular Functions (adhesion, morphology, migration, and invasion) in 2D or 3D environment. 4. Communication between (tumor) cells and microenvironments 5. 3D ECM-embedded cell culture or mouse models for TM4SF5-mediated fibrosis and metastasis 6. Nature of TM4SF5-mediated hepatic extracellular matrix (ECM) remodeling 7. Dynamics and nature of tetraspan(in) TM4SF5-enriched microdomains (T5ERMs) 8. Cellular and organellar cross-talks for nutrient homeostasis via T5ERM-mediated immuno-metabolic regulation 9. Dynamics and metabolic significance of intra- and inter-cellular T5ERMs 10. Nature of TM4SF5-mediated regulation of immune response during NAFLD and HCC 11. Study on TM4SF5-dependent immuno-metabolic regulation in non-alcholoic fatty (metabolic) liver disease 12. Study on clinical relevance of TM4SF5 to liver diseases 13. Investigation of TM4SF5 gene-engineered (TG and KO) animal models 14. Mechanistic regulation of TM4SF5 as an immune checkpoint for immune exhaustion 15. Development of diagnostic platforms for TM4SF5-dependent liver diseases 16. Development of anti-TM4SF5 reagents against liver diseases: anti-NASH, fibrosis, or tumor small compound or antibody?

Research goals

Research achievements

1. HE Song*, Y Lee*, E Kim*, CY Cho, O Jung, D Lee, SH Nam, M Kang, S JY Macalino, JE Kim, JW Jung, S Choi& and Lee JW& (Co-corresponding author) N-terminus-independent activation of c-Src via binding to a tetraspan(in) TM4SF5 in hepatocellular carcinoma is abolished by the TM4SF5 C-terminal peptide application. Theranostics. 2021. 11(16):8092-8111. 2. J. Ryu*, E. Kim*, M-K Kang, D-G Song, JW Jung, SH Nam, JE Kim, H-J Kim, J-H Lee, J-H Yoon, S Kim, and Lee JW (Corresponding author). Differential TM4SF5-mediated SIRT1 modulation and metabolic signaling in nonalcoholic steatohepatitis progression. Journal of Pathology. 2021. 253(1):55-67. 3. JW Jung, SJY. Macalino, M Cui, JE Kim, H-J Kim, D-G Song, SH Nam, S Kim, S Choi*, JW Lee* (Co-corresponding author). (2019). TM4SF5 Transmembrane 4 L six family member 5 senses arginine for mTORC1 signaling. Cell Metabolism. 29(6):1306-1319. 4. Nam, SH, Kim, D, Lee, D, Rhu J, Lee, H-M, Song, D-G, Jung, JW. Kim, JE, Kim, H-J, Kwon, NH, Jo,E-K, Kim, S, and Lee JW (Corresponding author). (2018). Lysyl-tRNA synthetase-expressing colon spheroids induce M2 macrophage polarization to promote metastasis. Journal of Clinical Investigation, 128(11):5034-5055. 5. H-M Ahn, J Ryu, JM Song, Y Lee, H-J Kim, I Choi, SJ Kim, Lee JW (Co-corresponding author), and S Kim. (2017). Anti-cancer Activity of Novel TM4SF5-Targeting Antibodies through TM4SF5 Neutralization and Immune Cell-Mediated Cytotoxicity. Theranostics. 7(3): 594 -613. 6. D Lee, JW Jung, M Kang, SH Nam, J Ryu, MS Lee, HJ Kim, HE Song, J Choi, GH Lee, TY Kim, SH Kim, H Kim, P Kim, and Lee JW (Corresponding author). (2015). TM4SF5/CD44 interaction-mediated self-renewal and circulating capacities of hepatocellular cancer cells. Hepatology. 61(6): 1978-1997. 7. S Choi, S-A Lee, TK Kwak, HJ Kim, MJ Lee, S-K Ye, S-H Kim, S Kim, and J.W. Lee (corresponding author). (2009). Cooperation between integrin 5 and tetraspan TM4SF5 regulates VEGF-mediated angiogenic activity Blood 113(8):1845-1855. 8. S-A Lee, H.W. Ryu, Y.M. Kim, S Choi, M Lee, T-G Gwak, H.J. Kim, M. Cho, K H Park, and J. W. Lee (corresponding authors). (2009). Blockade of tetraspan TM4SF5-mediated tumorigenic activity in hepatocytes by a synthetic compound. Hepatology, 49(4):1316-1325. 9. S-A Lee*, S-Y Lee*, I-H Cho, M-A Oh, E-S Kang, Y-B Kim, W D Seo, S Choi, J-O Nam, M T-Adachi, S Kitajima, S-K Ye, S Kim, Y-J Hwang, I-S Kim, K H Park, and J.W. Lee (corresponding author). (2008). Tetraspanin TM4SF5 mediates loss of contact inhibition through epithelial-mesenchymal transition in human hepatocarcinoma Journal of Clinical Investigation. 118(4): 1354-1366. * equally contributed

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