呂世正

Shr-Jeng Leu

聯絡方式

☏ 02-2826-7150 (Office);

02-2826-7000 轉65830 (Lab)

✉ sjleu@nycu.edu.tw

〒 研究大樓2樓R209

經歷

Current: Associate Professor, Department of Biotechnology and laboratory Science in Medicine, National Yang-Ming University
 
2003-2005: Postdoc training, Department of Microbiology and Immunology, Vanderbilt University School of Medicine
 
1996-2003: Ph.D., Department of Molecular Genetics, University of Illinois
 
1995-1996: Medical Technologist, Cheng-Hsin Rehabilitation Medical Center
 
1994-1995: T.A., Faculty of Medical Technology, National Yang-Ming University
 
1992-1994: M.S., Institute of Biochemistry, National Yang-Ming University
 
1988-1992: B.S., Faculty of Medical Technology, National Yang-Ming University
 
 
 

研究方向

  1. Recombinant protein expression and purification technologies
  2. The CCN protein family and diseases
  3. Cellular niches for hematopoietic cell development
  4. Cancer immunobiology
  My research interests focus on the roles of CCN protein family in angiogenesis, cancer biology, and tumor immunology—- Angiogenesis, the sprouting of new blood capillaries from the pre-existing vessels, is fundamental to a wide spectrum of physiological and pathological processes. Uncontrolled angiogenesis underlies a variety of human diseases including diabetic retinopathy, arthritis, atherosclerosis, and cancers. During tumor development, the change of surrounding micro-environment is crucial for the growth of tumor cells. The components in extracellular matrix (ECM) and stromal cells provide a productive micro-environment that help tumor growth, undergo angiogenic switch, and escape immune surveillance. In contrast to general ECM components that serve in maintenance of tissue integrity, many ECM-associated proteins can be placed in the category of matricellular proteins, including the CCN family. In light of the inducible pattern of their expression, as well as their multiple interactions with cell surface receptors and matrix proteins, matricellular CCN proteins can participate in the control of many essential biological processes including angiogenesis, hematopoiesis, inflammation, embryonic development, tissue remodeling, wound healing, and tumor growth.
 
    We are generating recombinant bioactive CCN proteins, testing their biological activities by cancer cells, dissecting their structure-function relationships, mapping active peptide motives of these factors, and searching their targeting receptors/molecules. We also plan to exploit genetically engineered mice to answer their in vivo roles. Ultimately, we hope the results may help to define roles of CCNs in cancer biology as well as develop useful tools for tumor diagnoses and therapies, including bioactive protein fragments, peptide mimetics, monoclonal antibodies, and uncovering novel cell surface receptors for tumor targeting. In addition, we are also setting up experiments to characterize functional roles of CCNs in blood cell development.
 
    We are also interested in developing the novel protein expression systems. Currently, we have established several baculovirus-expression systems, which allow the production of bioactive recombinant proteins by the eukaryotic insect cells. The proteins are expressed with the newly-designed tag sequences for sequential affinity column purifications. We have successfully achieved the affinity purification of several bioactive recombinant proteins that are previously challenging to be produced. We are currently using these recombinant proteins for many studies including biochemical analyses, development of monoclonal antibodies, bioimaging, and proteomic screenings.

研究著作

  1. Leu, S.J.*, Sung, J.S., Chen, M.Y., Chen, C.W., Cheng, J.Y., Wang, T.Y., and Wang, J.J. (*Corresponding author). (2013). The Matricellular Protein CCN1 Suppresses Lung Cancer Cell Growth by Inducing Senescence via the p53/p21 Pathway. J. Cell. Biochem.114(9): 2082-2093.
  2. Leu, S.J.*, Sung, J.S., Huang, M.L., Chen, M.Y., and Tsai, T.W. (*Corresponding author). (2013). A Novel Anti-CCN1 Monoclonal Antibody Suppresses Rac-Dependent Cytoskeletal Reorganization and Migratory Activities in Breast Cancer Cells. Biochem. Biophys. Res. Commun. 434(4): 885-891.
  3. Zhao, J.F.#, Leu, S.J.#, Shyue, S.K., Su, K.H., Wei, J., Lee, T.S.*(#equal contribution). (2013). Novel Effect of Paeonol on the Formation of Foam Cells: Promotion of LXRalpha-ABCA1-Dependent Cholesterol Efflux in Macrophages. American Journal of Chinese Medicine (in press).
  4. Lee, C.W., Leu, S.J., Tseng, R.Y., Wang, S.F., Tsai, S.C., Sun, K.H., Chen, R.H., and Huang, J.C. (2011). Latent membrane protein 1 of Epstein-Barr virus regulates death-associated kinase 1 in lymphoblastoid cell line. Virology 413: P.19-P.25.
  5. Ho, M.Y., Tang, S.J., Ng, W.V., Yang, W., Leu, S.J., Lin, Y.C., Feng, C.K., Sung, J.S., and Sun, K.H. (2010). The nucleotide-binding domain of phosphoglycerate kinase 1 reduces tumor growth by suppressing cyclooxygenase 2 expression. Cancer Sci. 101(11): 2411-2416.
  6. Ho, M.Y., Leu, S.J., Sun, G.H., Tao, M.H., Tang, S.J., and Sun, K.H. (2009). IL-27 Directly Restrains Lung Tumorigenicity by Suppressing Cyclooxygenase-2-Mediated Activities. J. Immunol. 183(10): P6217-6226.
  7. Lee, T.P., Leu, S.J., Huang, J.C., Song, Y.C., Jhou, R.S., Tang, S.J., Sun, K.H. (2008) Anti-ribosomal phosphoprotein autoantibody triggers interleukin-10 overproduction via phosphatidylinositol 3-kinase-dependent signalling pathways in lipopolysaccharide-activated macrophages. Immunology 127(1):91-102.
  8. Ho, M.Y., Sun, G.H., Leu, S.J., Ka, S.M., Tang, S.J., Sun, K.H. (2008). Combination of Fasl and GM-CSF confers synergistic antitumor immunity in an in vivo model of the murine Lewis lung carcinoma. Int. J. Cancer 123: P123-133.
  9. Lin, C.G., Chen, C.C., Leu, S.J., Grzeszkiewicz, T.M., and Lau, L.F.. (2005). Integrin-dependent functions of the angiogenic regulator CCN3 (NOV) in fibroblasts: implication in wound healing. J. Biol. Chem. 3(9):8229-8237.
  10. Chen, N., Leu, S.J., Todorovic, V., Lam, S.C.T., and Lau, L.F.. (2004). Identification of a Novel Integrin alphav beta3 Binding Site in CCN1(CYR61) Critical for Pro-angiogenic Activities in Vascular Endothelial Cells. J. Biol. Chem.1(42):44166-44176
  11. Leu, S.J., Chen, N., Chen, C.C., Todorovic V., Bai, T., Juric, V., Liu, Y., Yan, G., Lam, S.C.T., and Lau, L.F.. (2004). Targeted Mutagenesis of the Angiogenic Protein CCN1 (CYR61): Selective inactivation of integrin alpha6 beta1-heparan sulfate proteoglycan coreceptor-mediated cellular functions. J. Biol. Chem. 1(61):44177-44187
  12. Leu, S.J., Liu, Y., Chen, N., Chen, C.C., Lam, S.C.T., and Lau, L.F.. (2003). Identification of a novel integrin alpha6 beta1 binding site in the angiogenic inducer CCN1 (CYR61). J. Biol. Chem. 1(36):33801-33808
  13. Lin, C., Leu, S.J., Chen N., Tebeau, C.M., Lin, S.X., Yeung, C.Y., and Lau, L.F.. (2003). CCN3 (NOV) is a novel angiogenic regulator of the CCN protein family. J. Biol. Chem. 3(26):24200-24208
  14. Leu, S.J., Lam, S.C.T., and Lau, L.F. (2002). Pro-angiogenic activities of CYR61 (CCN1) mediated through integrins alphav beta3 and alpha6 beta1 in human umbilical vein endothelial cells. J. Biol. Chem. 277: 46248-46255.
  15. Leu, S.J., Chai, S.P., Kwok, C.F., and Fong, J.C. (1998). 4-Bromocrotonic acid enhances basal but inhibits insulin-stimulated glucose transport in 3T3-L1 adipocytes. Biochem. Biophys. Res. Commun. 244: 11-14. (M.S. thesis work).
  16. Fong, J.C., Leu, S.J., and Chai, S.P. (1997). Differential inhibition of lipolysis by 2-bromopalmitic acid and 4-bromocrotonic acid in 3T3-L1 adipocytes. Biochim. Biophys. Acta 1344: 65-73. (M.S. thesis work).
  17. Fong, J.C., Leu, S.J., and Hong, P.K. (1991). Enhanced lipolysis in 3T3-L1 adipocytes following prolonged exposure to tolbutamide. Biochem. Biophys. Res. Commun. 181: 1385-1391. (Undergraduate thesis work).

申請中或準備中的研究著作

  • The site-specific in vivo biotinylation of recombinant proteins using a dual BirA-acceptor peptide expression system. (submitted to Protein Expression and Purification).
  • Purification of bioactive CCN1 proteins using the dual FLAG/StrepII affinity chromatography scheme. (submitted to Protein Expression and Purification).
  • A monoclonal antibody specific for the matricellular CCN1 protein. (submitted to Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, formerly Hybridoma ).
  • The adipocytokine visfatin promotes breast cancer cell migration and invasion via the ERK-dependent pathway. (in preparation).
  • Vasohibin, an endothelium-derived angiogenesis inhibitor, is associated with the extracellular matrix and the cell surface. (in preparation).