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| Biography of Dr. Sheng-Xiang Lin |
 Sheng-Xiang Lin is a professor in Oncology and Molecular Endocrinology Research Center, Laval University Medical Center, Quebec, Canada. He received his Bachelor and Master's degrees in Shanghai Fu-Dan University and Shanghai Institute of Biochemistry, Academia Sinica, and then completed his doctoral degree with D.Sc. in CNRS and Louise-Pasteur University, France.
In his early research carrier, Professor Lin extensively studied the discrimination of amino acids by aminoacyl-tRNA synthetase by fast kinetics and binding studies. His results demonstrated a sophisticated multiple proofreading mechanism contributing to the fidelity of protein biosyntheses.
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In recent years, he developed a combined study of structure biology and enzymology, and resulted in novel findings in endocrinology and biochemistry. The latter is exemplified by the crystallization and structure determination of the first human steroid-converting enzyme, the 17beta-hydroxysteroid dehydrogenase 1, and its detailed structure-function study. Dr. Lin has demonstrated that the pseudo-symmetry of androgen structure made it possible to bind in the enzyme substrate site with alternative orientations and led to the inactivation of androgen hormones, notably, the most potent androgen DHT.
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More recently Prof. Lin is using the quantitative physico-biochemistry to integrate structural biology, enzymology, cell biology and proteomics together. The has proved that the dual activity of 17beta-HSD1 toward both estrogen and androgen is playing critical roles in human breast cancer cells, the increase of the former and the decrease of the later by 17beta-HSD1 stimulated the proliferation of the cancer cells (Mol Endocrinol, 2010, 24, 832-845).
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The above study laid down a novel basis for 17beta-HSD1 targeting against breast cancer. Moreover, estrogen is synthesized in a combined sulphatase and aromatase pathway, whose targeting is necessary to the cancer treatment. The candidate's proposal "Sulfatase and aromatase pathways for estradiol synthesis in human breast cancer cells, tissues and animal models: identifying a combinatory therapy" has been approved by CIHR. A review "Molecular Therapy of breast cancer: progress and future directions" summarized the cancer therapy in last decades and proposed new molecular therapy, is published very recently (Nature Reviews Endocrinology, 2011, 6, 485-493).
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Since the initiation of the first structural biology laboratory at Laval University in 1990, Prof. Lin has provided extensive collaboration to his colleagues in the university. A good number of protein structures have been determined with their structure-function analyzed in details, such as human 17beta-HSD1, 5 and 7, 3alpha-HSD3 and DHEA sulfotransferase in collaboration with other members of CIHR group in molecular endocrinology at Laval University Medical Center, in which several enzyme inhibitors have been rationally designed, and Chloramphenicol Acetyltransferase B2 from Tn2424 in collaboration with Prof. J. Lapointe and P. Roy, Proteo. The collaboration with Dr. G. Boivin from the center of infectiology has resulted in lead compounds against Herpes Simplex viruses RNA polymerase, demonstrating strong inhibitory capacity against the virus.
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Crystallography has provided the most entity of macromolecular structures to date (more than 86%) in PDB (protein data bank) since more than one century, but its pre-determining step, the crystallization, remains rate-limiting. Since the micro methods by A. Macpherson, and detailed analysis of crystallization parameters by R. Gieg¨¦ who proposed the new idea of crystallogenesis, of which the importance of the crystallization mechanism study has been received widely. Prof. Lin has worked intensively to improve this methodology, proposed the use of strong magnetic field to grow high quality crystals, the methods of crystallizing membrane associated proteins in complex with their hydrophobic ligands, and more recently a novel measurement of protein crystallizability. He chaired the ICCBM11 in Laval University in 2006. In his scientific career, Prof. Lin has also received the Commemorative Medal of 125th Anniversary of Canadian Confederation (1993), Special Award for international renowned scientists by University Laval, Junnior, senior and career scientist awards from FRSQ (1990-2004), Bai Yu Lan Prize for Outstanding Scientists nominated by the Shanghai municipality (1999). Prof. Lin has published more than 110 scientific articles, mostly in high level international journals, resulting in about 2800 citations.
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