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Shr-Jeng Leu
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Shr-Jeng Leu,  Ph.D

Associate Professor


Department of Molecular Genetics,  University  of  Illinois  at  Chicago

Postdoc Training: Department of Microbiology and Immunology,  Vanderbilt   University   School  of Medicine

02-2826-7000 ext. 7150 (Office)

02-2826-7000 ext. 5830 (Lab)

Office Location: Research building R209

E-Mail: sjleu@ym.edu.tw 

       sjim.leu@gmail.com


Research interests:
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 a bacterial inducible system that allows the efficient expression of recombinant proteins that are readily secreted into bacterial culture media. The protocol permits convenient collection of recombinant proteins of a high purity. We have also constructed 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. Another setting of a designed tag sequence permits the biotin ligase-dependent coupling of one small biotin molecule (MW 244) onto one individual target protein. This ensures site-specific biotin labeling within the target proteins and minimally affects their protein structures. Since the robust biotin/avidin interaction is versatile to be applied for many biological detections and analyses, we are currently using these biotin-labeled recombinant proteins for many studies including quantitative detection, bioimaging, and proteomic screening analyses.


Education and Work Experience
2005-current Assistant 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


Fellowships and Honors
2003 Recruiting Incentive for Excellence Award, Vanderbilt University
2003 Travel Award, Graduate School of the University of Illinois
2003 Travel Award, Ministry of Education, Taiwanese Government
1997-1998 University Fellowship Award, University of Illinois at Chicago
1993 Graduate Scholarship (1st prize), National Yang-Ming University
1988-1992 Undergraduate Scholarships, Yang-Ming-Shan Bank of Taipei


Publish
1. Ho, M.Y., Tang, S.J., Ng, W.V., Yang, W., Leu, S.J., Lin, Y.C., Feng, C.K., Sung, J.S., Sun, K.H. The nucleotide-binding domain of phosphoglycerate kinase 1 reduces tumor growt by suppressing cyclooxygenase 2 expression. (2010) Cancer Sci. (In press)
2. Ho, M.Y., Leu, S.J., Sun, G.H., Tao, M.H., Tang, S.J., and Sun, K.H. IL-27 Directly Restrains Lung Tumorigenicity by Suppressing Cyclooxygenase-2-Mediated Activities. (2009) J. Immunol 183(10): 6217-6226.

3. Ho, M.Y., Sun G.H., Leu, S.J., Ka, S.M., Tang, S.J., and 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. Can. 123(1):123-133.

4. 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.

5. 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. 280: 8229-37.

6. 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 inducer CCN1 (CYR61) inactivating functions mediated through integrin alpha6beta1-heparan sulfate proteoglycan coreceptors. J. Biol. Chem. 279: 44177-87.

7. Chen, N., Leu, S.J., Todorovic, V., Lam, S.C.T., and Lau, L.F. (2004). A novel integrin alphaVbeta3 binding site in the angiogenic inducer CCN1 (CYR61) is critical for promoting endothelial cell proliferation and survival. J. Biol. Chem. 279: 44166-76.

8. Leu, S.J., Liu, Y., Chen, N., Chen, C.C., Lam, S.C.T., and Lau, L.F. (2003). Identification of a novel integrin alpha6beta1 binding site in the angiogenic inducer CCN1 (CYR61). J. Biol. Chem. 278: 33801-8.

9. 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. 278: 24200-8.

10. Leu, S.J., Lam, S.C.T., and Lau, L.F. (2002). Pro-angiogenic activities of CYR61 (CCN1) mediated through integrins alphaVbeta3 and alpha6beta1 in human umbilical vein endothelial cells. J. Biol. Chem. 277: 46248-46255.

11. 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).

12. 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).

13. 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).

Manuscripts under preparation and submission (as the corresponding author).
1. The adipocytokine visfatin promotes breast cancer cell migration and invasion via the ERK-dependent pathway.
2. The site-specific in vivo biotinylation of recombinant proteins using a dual BirA-acceptor peptide expression system.
3. Purification of bioactive CCN1 proteins using the dual FLAG/StrepII affinity chromatography scheme.
4. Vasohibin, an endothelium-derived angiogenesis inhibitor, is associated with the extracellular matrix and the cell surface.


Updated date: July, 2010