Sachdev S. Sidhu 博士

发布者:免疫所发布时间:2019-11-14浏览次数:49

  Sachdev S. Sidhu 博士

Distinguished Adjunct Professor

Principal Investigator
Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University
Email: sssidhu@@shanghaitech.edu.cn
Director and Founder, The Centre for the Commercialization of Antibodies and Biologics (a Centre of Excellence for Commercialization and Research Program, Networks of Centres of Excellence of Canada), University of Toronto;
Professor, Banting and Best Department of Medical Research, University of Toronto;
sachdev.sidhu@gmail.com
sachdev.sidhu@utoronto.ca
Fax: (203) 785-4305

Laboratory: Lab of Antibody Engineering

Positions and Employment
2014-present Director and Founder, The Centre for the Commercialization of Antibodies and Biologics (a Centre of Excellence for Commercialization and Research Program, Networks of Centres of Excellence of Canada), University of Toronto
2013-present Professor, Banting and Best Department of Medical Research, University of Toronto
2008-2013 Associate Professor, Banting and Best Department of Medical Research, University of Toronto
2004-2008 Senior Scientist, Department of Protein Engineering, Genentech, Inc.
1998-2004 Scientist, Department of Protein Engineering, Genentech, Inc.

Additional Affiliations
2008-present Principal Investigator, The Donnelly Centre, University of Toronto 
2008-present Senior Investigator - Ontario Institute for Cancer Research
2008-present Professor, Department of Molecular Genetics, University of Toronto


Academic and Training Background
1996-1998 Postdoctoral Fellow, Department of Protein Engineering, Genentech, Inc.
1996 Ph.D. Biochemistry, Simon Fraser University 
1990 B.Sc. Biochemistry, First Class Honours, Simon Fraser University

Selected Accomplishments and Honours
1996-1998 Postdoctoral Fellow, Department of Protein Engineering, Genentech, Inc.
1996 Ph.D. Biochemistry, Simon Fraser University 
1990 B.Sc. Biochemistry, First Class Honours, Simon Fraser University

Dr. Sachdev Sidhu is an expert in phage display technology and structure-based and combinatorial protein engineering. In 2008, after spending a decade as a principal investigator in the Department of Protein Engineering at Genentech, Inc., Dr. Sidhu joined the University of Toronto to start his academic lab.

At Genentech, Dr. Sidhu led the development of phage-displayed synthetic antibody libraries that have since proven to be a rich source of valuable reagents for basic research and potential therapeutics. In addition to antibody engineering, Dr. Sidhu has extensive experience with phage display of other diverse polypeptides, including peptides, peptide-binding domains, hormones and antibody mimics.

The Sidhu lab’s talented scientists, students, technicians and others contribute to several projects, and Dr. Sidhu has a successful track record of collaborations with both academic and industry partners, including Drs. Moffat, Kossiakoff, Koide, Boone, Neel, Rottapel, Shoichet and Reilly and Integrated BioTherapeutics, Genentech, GlaxoSmithKline, Merrimack and Alnylam Pharmaceuticals, respectively. Research in the lab is supported by extensive funding from both public and private sources, including large team grants from Genome Canada and the Ontario Research Fund, to address specific unmet medical needs using protein binders.

In 2011, Dr. Sidhu expanded his laboratory by launching the Toronto Recombinant Antibody Centre (TRAC), an integrated laboratory with a state-of-the-art, high throughput antibody research platform that has been applied to the generation of therapeutic-grade antibodies against hundreds of antigens.

The Sidhu lab is located in the Terrence Donnelly Centre for Cellular and Biomolecular Research (The Donnelly Centre) as well as in the Best Institute, and Dr. Sidhu is a Professor in the Banting and Best Department of Medical Research (BBDMR) at the University of Toronto. The Donnelly Centre provides a highly motivating collaborative environment, as well as access to state-of-the-art equipment, technology, expertise and services. The Sidhu lab is well outfitted with all the equipment necessary for phage display and for protein purification and analysis, including customized robotics for expediting phage selections and screens.

In addition to his primary appointment as a professor in the BBDMR and principal investigator at CCBR, Dr. Sidhu is also an associate investigator at the Ontario Institute for Cancer Research (OICR) and is cross-appointed in the Department of Molecular Genetics at the University of Toronto.

Research Interest
The Sidhu Lab interests lie in the field of protein engineering and technologies that explore and shape protein structure and function. The lab uses in vitro evolution to recreate Darwinian selections inside a test tube. We investigate the function of natural proteins and design changes to improve function and reverse the effects of disease.

Going further, we can also construct synthetic proteins designed to target proteins inside cells, in much the same as the immune system produces antibodies to target infectious invaders.

Significance
Better understand the molecular basis of cellular function and to use this knowledge to develop therapies for cancer, diabetes and other diseases.

Selected publications
· Ernst, A., Appleton, B. A., Ivarsson, Y., Zhang, Y., Gfeller, D., Wiesmann, C & Sidhu, S. S. (2014) A structural portrait of the PDZ domain family. J. Mol. Biol. 426(21):3509-19
· Chen, G., Koellhoffer, J. F., Zak, S. E., Frei, J. C., Liu, N., Long, H., Yi, W., Nagar, K., Pan, G., Chandran, K., Dye, J. M., Sidhu, S. S. & Lai, J. R. (2014) Synthetic Antibodies with a Human Framework that Protect Mice from Lethal Sudan Ebolavirus Challenge. ACS Chem Biol. 9(10):2263-73
· Shukla, A. K., Westfield, G. H., Xiao, K., Reis, R. I., Huang, L. Y., Tripathi-Shukla, P., Qian, J., Li, S., Blanc, A., Oleskie, A. N., Dosey, A. M., Su, M., Liang, C. R., Gu, L. L., Shan, J. M., Chen, X., Hanna, R., Choi, M., Yao, X. J., Klink, B. U., Kahsai, A. W., Sidhu, S. S., Koide, S., Penczek, P. A., Kossiakoff, A. A., Woods Jr, V. L., Kobilka, B. K., Skiniotis, G. & Lefkowitz, R. J. (2014) Visualization of arrestin recruitment by a G-proteincoupled receptor. Nature 512, 218-22.
· Ni, Z., Xu, C., Guo, X., Hunter, G. O., Kuznetsova, O. V., Tempel, W., Marcon, E., Zhong, G., Guo, H., Kuo, W. H., Li, J., Young, P., Olsen, J. B., Wan, C., Loppnau, P., El Bakkouri, M., Senisterra, G. A., He, H., Huang, H., Sidhu, S. S., Emil, A., Murphy, S., Mosley, A. L., Arrowsmith, C. H., Min, J. & Greenblatt, J. F. (2014) RPRD1A and RPRD1B are human RNA polymerase II C-terminal domain scaffolds for Ser5 dephosphorylation. Nat. Struct. Mol. Biol. 21, 686-95.
· Murciano-Calles, J., McLaughlin, M. E., Erijman, A., Hooda, Y., Chakravorty, N., Martinez, J. C., Shifman, J. M., Sidhu, S. S. (2014) Alteration of the C-terminal ligand specificity of the Erbin PDZ domain by allosteric mutational effects. J. Mol. Biol. 426(21):3500-8· Gfeller, D., Ernst, A., Jarvik, N., Sidhu, S. S. & Bader, G. D. (2014) Prediction and experimental characterization of nsSNPs altering human PDZ-binding motifs. PLoS One 9, e94507.
· Adams, J. J. & Sidhu, S. S. (2014) Synthetic antibody technologies. Curr. Opin. Struct. Biol. 24C, 1-9.
· Abu-Odeh, M., Bar-Mag, T., Huang, H., Kim, T., Salah, Z., Abdeen, S. K., Sudol, M., Reichmann, D., Sidhu, S. S., Kim, P. M. & Aqeilan, R. I. (2014) Characterizing WW Domain Interactions of Tumor Suppressor WWOX Reveals its Association with Multiprotein Networks. J. Biol. Chem. 28, 8865-80.
· Ivarsson, Y., Arnold, R., McLaughlin, M., Nim, S., Joshi, R., Ray, D., Liu, B., Teyra, J., Pawson, T., Moffat, J., Li, S.-S., Sidhu, S. S. & Kim, P. M. (2014) Large-scale interaction profiling of PDZ domains through proteomic peptide-phage display using human and viral phage peptidomes. Proc. Natl. Acad. Sci. USA 111, 2542-7.
· Chen, G. & Sidhu, S. S. (2014) Design and generation of synthetic antibody libraries for phage display. Methods Mol. Biol. 1131, 113-31.
· Liu, P., Cai, Z., Kang, J. W., Boyle, A. J., Adams, J., Lu, Y., Mbong, G. N., Sidhu, S. S., Reilly, R. M. & Winnik, M. A. (2014) Intracellular Routing in Breast Cancer Cells of Streptavidin-Conjugated Trastuzumab Fab Fragments Linked to Biotinylated Doxorubicin-Functionalized Metal Chelating Polymers. Biomacromolecules 15, 715-25.
· Yu, C. G., Tonikian. R., Felsensteiner, C., Jhingree, J. R., Desveaux, D., Sidhu, S. S. & Harris, T. J. (2014) Peptide binding properties of the three PDZ domains of bazooka (Drosophila par-3). PLoS One 9, e86412.
· Rojas, G., Pupo, A., Leon, K., Avellanet, J., Carmenate, T. & Sidhu, S. (2013) Deciphering the molecular bases of the biological effects of antibodies against Interleukin-2: a versatile platform for fine epitope mapping. Immunobiology 218, 105-13.
· Persson, H., Ye, W., Wernimont, A., Adams, J. J., Lam, R. & Sidhu, S. S. (2012) CDR-H3 Diversity is Not Required For Antigen Recognition by Synthetic Antibodies. J. Mol. Biol. 425, 803-11.
· Ahmed, S. M., Thériault, B. L., Uppalapati, M., Chiu, C. W., Gallie, B. L., Sidhu, S. S. & Angers, S. (2012) KIF14 negatively regulates Rap1a-Radil signaling during breast cancer progression. J. Cell Biol. 199, 951-67.
· Miersch, S. & Sidhu, S. S. (2012) Immunology: Evolving superkines for selectivity. Nat. Chem. Biol. 8, 955-6.
· Koellhoffer, J. F., Chen, G., Sandesara, R. G., Bale, S. Saphire, E. O., Chandran, K., Sidhu, S. S. & Lai, J. R. (2012) Two synthetic antibodies that recognize and neutralize distinct proteolytic forms of the Ebola virus envelope glycoprotein. Chembiochem. 13, 2549-57.
· Orava, E. W., Jarvik, N., Shek, Y. L., Sidhu, S. S. & Gariepy, J. (2013) A short DNA Aptamer that Recognizes TNFαand blocks its activity in vitro. ACS Chem. Biol. 8, 170-8.
· Kaneko, T., Huang, H., Cao, X., Li, X., Li, C., Voss, C., Sidhu, S. S. & Li, S. S. (2012) Superbinder SH2 domains act as antagonists of cell signaling. Sci. Signal. 5, ra68.
· Mandal, K., Uppalapati, M., Ault-Riche, D., Kenney, J., Lowitz, J., Sidhu, S. S., Kent, S. B. (2012) Chemical synthesis and X-ray structure of a heterochiral {D-protein antagonist plus vascular endothelial growth factor} protein complex by racemic crystallography. Proc. Natl. Acad. Sci. USA 109, 14779-84.
· Miller, K. R, Koide, A., Leung, B., Fitzsimmons, J., Yoder, B., Yuan, H., Jay, M., Sidhu, S. S., Koide, S. & Collins, E. J. (2012) T cell receptor-like recognition of tumor in vivo by synthetic antibody fragment. PLoS One 7, e43746.
· Tonikian, R. & Sidhu, S. S. (2012) Selecting and purifying autonomous human variable heavy (VH) domains. Methods Mol. Biol. 911, 327-53. · Zalatan, J. G, Coyle, S. M., Rajan, S., Sidhu, S. S. & Lim, W. A. (2012) Conformational control of the Ste5 scaffold protein insulates against MAP kinase misactivation. Science 337, 1218-22.
· Miersch, S. & Sidhu, S. S. (2012) Synthetic antibodies: concepts, potential and practical considerations. Methods 57, 486-98.
· Nelson, B. & Sidhu, S. S. (2012) Synthetic antibody libraries. Methods Mol. Biol. 899, 27-41.
· Geyer, C. R., McCafferty, J., Dübel, S., Bradbury, A. R. & Sidhu, S. S. (2012) Recombinant antibodies and in vitro selection technologies. Methods Mol. Biol. 901, 11-32.
· Mandal, K., Uppalapati, M., Ault-Riche, D., Kenney, J., Lowitz, J., Sidhu, S. S., Kent, S. B. (2012) Chemical synthesis and X-ray structure of a heterochiral {D-protein antagonist plus vascular endothelial growth factor} protein complex by racemic crystallography. Proc. Natl. Acad. Sci. USA 109, 14779-84.
· Miller, K. R, Koide, A., Leung, B., Fitzsimmons, J., Yoder, B., Yuan, H., Jay, M., Sidhu, S. S., Koide, S. & Collins, E. J. (2012) T cell receptor-like recognition of tumor in vivo by synthetic antibody fragment. PLoS One 7, e43746.
· Tonikian, R. & Sidhu, S. S. (2012) Selecting and purifying autonomous human variable heavy (VH) domains. Methods Mol. Biol. 911, 327-53.
· Zalatan, J. G, Coyle, S. M., Rajan, S., Sidhu, S. S. & Lim, W. A. (2012) Conformational control of the Ste5 scaffold protein insulates against MAP kinase misactivation. Science 337, 1218-22.
· Miersch, S. & Sidhu, S. S. (2012) Synthetic antibodies: concepts, potential and practical considerations. Methods 57, 486-98.
· Nelson, B. & Sidhu, S. S. (2012) Synthetic antibody libraries. Methods Mol. Biol. 899, 27-41.
· Geyer, C. R., McCafferty, J., Dübel, S., Bradbury, A. R. & Sidhu, S. S. (2012) Recombinant antibodies and in vitro selection technologies. Methods Mol. Biol. 901, 11-32.
· Teyra, J., Sidhu, S. S. & Kim, P. M. (2012) Elucidation of the binding preferences of peptide recognition modules: SH3 and PDZ domains. FEBS Lett. 586, 2613-7.
· Sidhu, S. S. (2012) Antibodies for All: The Case for Genome-wide Affinity Reagents. FEBS Lett. 586, 2778-9.
· Karauzum, H., Chen, G., Abaandou, L., Mahmoudieh, M., Boroun, A. R., Shulenin, S., Devi, V. S., Stavale, E., Warfield, K. L., Zeitlin, L., Roy, C. J., Sidhu, S. S. & Aman, M. J. (2012) Synthetic human monoclonal antibodies towards staphylococcal enterotoxin B (SEB) protective against toxic shock syndrome. J. Biol. Chem. 287, 25203-15.
· Laver, J. D., Ancevicius, K., Sollazzo, P., Westwood, J. T., Sidhu, S. S., Lipshitz, H. D. & Smibert, C. A. (2012) Synthetic antibodies as tools to probe RNA-binding protein function. Molec. Biosyst. 8, 1650-7.
· Kim, T., Tyndel, M. S., Huang, H., Sidhu, S. S., Bader, G. D., Gfeller, D. & Kim, P. M. (2012) MUSI: an integrated system for identifying multiple specificity from very large peptide or nucleic acid data sets. Nucl. Acids Res. 40, e47.
· McCluskey, A. J., Bolewska-Pedyczak, E., Jarvik, N., Chen, G., Sidhu, S. S. & Gariépy, J. (2012) Charged and hydrophobic surfaces on the a chain of shiga-like toxin 1 recognize the C-terminal domain of ribosomal stalk proteins. PLoS One 7, e31191.
· Rajan, S. & Sidhu, S. S. (2012) Simplified synthetic antibody libraries. Methods Enzymol. 502: 3-23.