Dr. Pelech’s research involves mapping of the architecture of protein phosphorylation-based cell signaling networks to define phosphoprotein biomarkers for diagnosis and protein kinases and phosphatases as therapeutic targets. His team is using a combination of high throughput proteomics with protein microarrays and advanced bioinformatics to develop predictive algorithms for quantitative proteomics for studying protein expression and phosphorylation, and protein-protein and protein-drug interactions.
protein kinases, protein phosphorylation, protein phosphatases, signal transduction; cell signaling; Alzheimer’s disease; neurological disorders; cancer; diabetes; high throughput proteomics; microarrays; bioinformatics
The human genome appears to encode about 21,300 different proteins that feature around 1 million phosphosites, which are phosphorylated by ~568 protein kinases and dephosphorylated by ~156 protein phosphatases. Over 250 human diseases, including cancer, diabetes and a wide range of neurological and immunological disorders, appear to arise from defective protein phosphorylation from gene mutations and environmental toxins. Dr. Pelech’s research is using novel protein microarrays, immunoblotting and mass spectrometry to track thousands of phosphosites and hundreds of kinases to reconstruct the architecture of complex molecular communication networks that operate in cells that mediate cell survival, proliferation and function. His group is also producing novel computer programs that provide quantitative predictions of protein kinase and phosphosite interactions to define critical connections that when defective cause disease. This information has been used to create over 1200 antibody probes and 1600 synthetic peptide to serve as molecular diagnostic tools to facilitate personalized medicine. Kinetek Pharmaceuticals, Inc. (acquired by QLT, Inc.) and Kinexus Bioinformatics Corporation are two biotech companies that have spun-out of his UBC research program that have directly enabled cell communication research in more than 2000 academic and industrial laboratories world-wide in over 35 countries.
Dr. Pelech has a broad range of interests that include the study of molecular, cellular and social intelligence systems, evolution, history, archeology, sociology, geology and space sciences as well as the arts, including fine arts, graphic arts and photography.
- Binukumar, B.K., Shukla, V., Amin, N.D., Bhaskar, M., Skuntz, S., Steiner, J., Winkler, D., PELECH, S.L., and Pant, H.C. Analysis of the inhibitory elements in the p5 peptide fragment of the CDK5 activator, p35, CDKR1 Protein. J. Alzheimers Dis. 48(4):1009-17 (2015).
- Binukumar, B.K., PELECH, S.L., Sutter, C., Shukla, V., Amin, N.D., Grant, P., Bhaskar, M., Skuntz, S., Steiner, J., and Pant, H.C. Profiling of p5, a 24 amino acid inhibitory peptide derived from the CDK5 activator, p35 CDKR1 against 70 protein kinases. J. Alzheimers Dis. 54(2):525-33 (2016).
- Lai, S., and PELECH, S.L. Regulatory roles of conserved phosphorylation sites in the activation T-loop of the MAP Kinase ERK1. Mol. Biol. Cell 27(6):1040-50 (2016).
- Lai, S., Safaei, J., and PELECH, S.L. Eukaryotic protein kinases and choline kinases share a common ancestor related to ancient glutaminyl-tRNA synthetase. J. Biol Chem. 291(10):5199-205 (2016).
- Zhang, H., Shi, X., and PELECH, S. Monitoring protein kinase expression and phosphorylation in cell lysates with antibody microarrays. Protein kinase screening and Profiling. Edited by Hicham Zegzouti and Said Goueli. Humana Press USA. Methods in Molecular Biology 1360:107-22 (2016).
- Lai, S., Winkler, D.F.H., Zhang, H. and PELECH, S. Determination of the substrate specificity of protein kinases with peptide micro- and macroarrays. Protein kinase screening and Profiling. Edited by Hicham Zegzouti and Said Goueli. Humana Press USA. Methods in Molecular Biology 1360:183-202 (2016).
- Bhargava, A., PELECH, S.L., Woodard, B., Kerwin, J., Maherali, N., Reproducibility Project: Cancer Biology (Iorns, E., Gunn, W., Tan, F., Lomax, J., Perfito, N., Errington, T.). Registered Report: RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth. eLife 5. pii: e09976. doi: 10.7554/eLife.09976 (2016).
- Yue, L., Sam, C., Arora, N., Winkler, D.F.H., and PELECH, S. Antibody microarray and immunoblotting analyses of the EGF signaling phosphorylation network in human A431 epidermoid carcinoma cells. Clin. Proteom. Bioinform. 2(1): 1-10 (2017). DOI: 10.15761/CPB.1000119.
- Yue, L., and Pelech, S. Applications of high content antibody microarrays for biomarker discovery and tracking cellular signaling. Advances in Proteomics and Bioinformatics 1: 1-24 (2018). DOI: 10.29011/APBI -107. 100007.
- Fardilha, M., Esteves, S.L.C., Korrodi-Gregorio, L., PELECH, S., Cruz e Silva, O.A.B., and Cruz e Silva, E. Protein phosphatase 1 complexes modulate sperm motility and present novel targets for male infertility. Mol Hum Reprod. 17(8):466-77 (2011).
- Davies, A.H., Barrett, I., Pambid, M.R., Hu, K., Stratford, A.L., Freeman, S., Berquin, I.M., PELECH, S., Hieter, P., Maxwell, C., Dunn, S.E. YB-1 evokes susceptibility to cancer through cytokinesis failure, mitotic dysfunction and HER2 amplification. Oncogene. 30(34):3649-60 (2011).
- Carter, C.A., Misra, M., PELECH, S. Proteomic analyses of lung lysates from short-term exposure of Fischer 344 rats to cigarette smoke. J Proteome Res. 10(8):3720-31 (2011)
- Rogers, L.D., Brown, N.F., Fang, Y., PELECH, S. and Foster, L.J. SopB is a master regulator of host signaling cascades during Salmonella infection. Sci Signal. 4(191):rs9 (2011).
- Safaei, J., Manuch, J., Gupta, A., Stacho, L. and PELECH, S. Prediction of 492 human protein kinase substrate specificities. Proteome Science 9(Suppl 1):S6; 1-13 (2011).
In addition to original scientific research articles, Dr. Pelech has produced over 300 blog commentaries as part of an outreach effort to inform the broader scientific community on a wide range of issues ranging from career development to genomics to biotechnology. Over 270 of these commentaries have appeared at the GenomeWeb website and are also featured at the www.kineticaonline.ca website under “Blog Commentaries”.
In recent years, Dr. Pelech’s laboratory in collaboration with Kinexus Bioinformatics Corporation has also developed and launched several open-access, on-line databases available in the SigNET KnowledgeBank, which features over 1.4 million webpages. KiNET-AM (www.kinet-am.ca) holds the results from over 3000 analyses of diverse cell and tissue lysates with antibody microarrays. The PhosphoNET KnowledgeBase (www.phosphonet.ca) contains annotated information on over 180,000 confirmed and 790,000 putative phosphorylation sites in over 21,000 human proteins, their evolutionary conservation in 22 other species, prediction of the top 50 human kinases that target each phosphosite, and identification of related phosphosites. Other specific knowledgebases include those for human protein kinases (www.kinasenet.ca), human gene expression (www.transcriptonet.ca), cancer-related proteins (www.onconet.ca), kinase-drug interactions (www.drugkinet.ca) and protein-drug interactions based on x-ray crystallographic data (www.drugpronet.ca)¬. Many protein-protein and kinase-drug interactions are graphically depicted in the KinATLAS website (www.kinatlas.ca:8080).
- 1988-1993 Medical Research Council of Canada Scholarship Award
- 1993-1996 Medical Research Council of Canada Scientist Award
- 1996-1998 Medical Research Council of Canada Industrial Scientist Award
- 1993 Canadian Society for Biochemistry & Molecular Biology Merck-Frosst Award for Outstanding Research
- 1993 Martin M. Hoffman Award – University of B.C. Hospital Site for Research in Dept. of Medicine
- 1996 Business in Vancouver Top Forty Under Forty Award for Business Achievement
- 2001 Faculty of Medicine 2001 Distinguished Lecturer, University of B.C.
Dr. Pelech has not received direct funding from granting agencies to his UBC research laboratory for the last 10 years. Previously, Dr. Pelech was the recipient of CDN$ 4,141,970 in grant funding from various agencies as sole principal investigator. His current research support is provided primarily through Kinexus Bioinformatics Corporation.
For the past 28 years, Dr. Pelech has been very active in the establishment of the Experimental Medicine (ExMed) Graduate Program and has worked closely with its six directors (i.e. Drs. Rabkin, Quamme, Wong, Duronio, Sly and Tang) on the ExMed executive committee since its inception. His aim has been to develop graduate level courses that would provide practical and useful skills to M.Sc. and Ph.D. students. In particular, the students should acquire a solid knowledge base, be able to read the scientific literature and on-line websites critically, adapt to new lab environments and assimilate new techniques, deliver clear oral presentations, and write competitive grants for funding. Dr. Pelech reviews admissions of students and faculty into the ExMed Graduate Program, and he also participates in judging scholarship awards submitted through the program.
Dr. Pelech currently coordinates and delivers all of the lectures (~46 hours) in the MEDI-590 course on advanced molecular regulation of cells, and a 1.5 hour lecture in the MEDI-501 core course in the Experimental Medicine Graduate Program. He also hosts one to two graduate students per year in the MEDI-502 course for their lab rotations. Through Kinexus Bioinformatics Corporation, Dr. Pelech has been a mentor and supervisor of over 160 undergraduate students from UBC and Simon Fraser University through their coop programs. He typically supervises two to four undergraduate students in full-time terms of 4 to 12 months. Dr. Pelech has also been the direct supervisor of one to three Ph.D. graduate students over the last four years. He also mentors one to two teams of three to five computer science students from the B.C. Institute of Technology in website development projects annually.