Professor and ChairPh.D., Friedrich-Alexander University in Erlangen, Germany
Toronto Medical Discovery Tower
101 College Street, Room 9-807
Toronto, Ontario M5G 1L7
Lab Phone: 416-581-7644
Email Dr. Thomas Kislinger
Link to personal website
At A Glance:• Focus of the lab includes proteomics, mass spectrometry and cancer biology
• Integration of multiple omics technology and focus on proteogenomics
• Development of novel technologies for identification and quantification of novel surface proteins (membrane proteomics)
• Translational research and close collaboration with clinicians to develop relevant biomarker signatures
• Development of highly multiplexed proteomics quantification strategies for biomarker verification
Thomas Kislinger received his MSc in Analytical Chemistry from the University of Munich, Germany (1998). He completed his PhD in 2001, investigating the role of Advanced Glycation Endproducts in diabetic vascular complications at the University of Erlangen, Germany and Columbia University, New York. Between 2002 and 2006 he completed a post-doctoral fellowship at the University of Toronto using shotgun proteomics to investigate organelle dynamics in mouse models of human disease. In 2006 he joined the Princess Margaret Cancer Center as an independent investigator. Dr. Kislinger holds positions as Senior Scientist at the Princess Margaret Cancer Center and as Associate Professor at the University of Toronto in the Department of Medical Biophysics. He is a Tier 2 Canadian Research Chair in Proteomics in Cancer Research. The research interests in the Kislinger lab are focused on the application of proteomics and computational tools to cancer biology and biomarker discovery. We are particularly interested in combining in-depth proteomics with chemistry, biochemistry and cell & molecular biology to gain novel insights into the function of poorly studied membrane proteins.
Organelle Proteomics: Since 2002 I have been actively developing and applying methods that combine the isolation of organelles with in-depth proteomics analyses (Cell, 2006). Since starting my own research group at the Princess Margaret Cancer Center, we have continued to work on this topic. In 2009 my lab published the first direct comparison of an analogous human and mouse tissue, on the proteome level. Carefully microdissected human villous tissue was compared to mouse labyrinth, both by organellar proteomics and microarray analysis. We were able to detect approximately 7,000 orthologous genes and demonstrate 70% co-expression in both species (Molecular Systems Biology, 2009). We are now interested in applying our expertise in cellular fractionation, proteomics and multi-omic integration to the emerging field of onco-proteogenomics (Nature Methods, 2014).
Cell Surface Mapping: Plasma membrane proteins are essential mediators of cell signalling and cellular communication. Due to their hydrophobicity and low abundance they have been traditionally underrepresented in proteomic analyses. For the last ten years, my group has been developing proteomics methods for the comprehensive analysis of the “surfaceome” (Nature Communications, 2015; Developmental Cell, 2012; Molecular & Cellular Proteomics, 2011). We have initiated a number of programs that comprehensively map the surfaceome of relevant cancer models with the goal to identify novel targets for antibody-drug conjugates and for functional investigations.
Cancer Biomarker Discovery & Targeted Quantification: My lab has been among the first to utilize expressed prostatic secretions (EPS), a tissue proximal fluid, for the discovery of novel prostate cancer biomarkers. We rationalized that this fluid contains prostate secreted/shed proteins are in a significantly higher concentration as compared to blood, hence enabling the detection of novel protein biomarker candidates. To date we have published a number of proof-of-concept studies providing a detailed description of these clinically relevant fluids (Journal of Proteome Research 2010 & 2012; Molecular & Cellular Proteomics, 2012; Proteomics, 2013). We are currently validating a large number of candidate proteins in richly annotated EPS-urines by targeted proteins (i.e. Selected Reaction Monitoring Mass Spectrometry - SRM-MS). In addition, we are actively implementing a novel quantification approach, termed Parallel Reaction Monitoring Mass Spectrometry (PRM-MS) for future biomarker discovery/verification projects.
List of Key Publications:
1. Kim Y, Jeon J, Mejia S, Yao CQ, Ignatchenko V, Nyalwidhe JO, Gramolini AO, Lance RS, Troyer DA, Drake RR, Boutros PC, Semmes OJ & Kislinger T. Targeted proteomics identifies liquid-biopsy signatures for extracapsular prostate cancer. Nat Commun 2016 June 28;7:11906
2. Sharma P, Bousette N, Lazic S, Abbasi C, Dubois N, Ignatchenko A, Ignatchenko V, Teng A, Wilson A, Liu J, Noronha M, Wong V,Araki T, Massé S, Nanthakumar K, Tiburcy M, Zimmermann WH, Hamilton R, Liu PP, Backx PH, Keller G, Stagljar I, Scott IC, Kislinger T* & Gramolini AO*. Evolutionarily conserved intercalated disc protein Tmem65 regulates cardiac conduction and connexin 43 function. Nat Commun. 2015 Sep 25;6:8391. *co-senior authors
3. Alfaro JA, Sinha A, Kislinger T* & Boutros PC*. Onco-proteogenomics: Cancer Proteomics Joins Forces with Genomics. Nat Methods 2014; 11 (11): 1107-1113. *co-senior authors
4. Sepiashvili L, Waggott D, Hui A, Shi W, Su S, Ignatchenko A, Ignatchenko V, Laureano M, Huang SH, Xu W, Weinreb I, Waldron J, O’Sullivan B, Irish JC, Boutros PC, Liu FF & Kislinger T. Integrated Omic Analysis of Oropharyngeal Carcinomas Reveals HPV-dependent Regulation of the AP-1 Pathway. Mol Cell Proteomics 2014 Dec;13(12):3572-3584
5. Kim Y, Ignatchenko V, Yao C, Nyalwidhe JO, Boutros P, Kalatskaya I, Lance RS, Gramolini AO, Troyer DA, Semmes OJ, Medin JA, Drake RR & Kislinger T. Identification of differentially expressed proteins in direct expressed prostatic secretions of men with organ-confined versus extracapsular prostate cancer. Mol Cell Proteomics 2012; 11: 1870-1884.
6. Sepiashvili L, Hui A, Ignatchenko V, Shi W, Su S, Xu W, Huang SH, O'Sullivan B, Waldron J, Irish JC, Perez-Ordonez B, Liu FF & Kislinger T. Potentially Novel Candidate Biomarkers for Head and Neck Squamous Cell Carcinoma Identified Using an Integrated Cell Line-based Discovery Strategy. Mol Cell Proteomics 2012; 11: 1404-1415.
7. Rugg-Gunn P, Cox BJ, Lanner F, Sharma P, Ignatchenko V, Garner J, Gramolini AO, Rossant J, & Kislinger T. Cell surface proteomics identifies lineage-specific markers of embryo-derived stem cells. Dev Cell 2012; 22: 887-901.
8. Cox B, Sharma P, Evangelou AI, Whiteley K, Ignatchenko V, Ignatchenko A, Baczyk D, Czikk M, Kingdom J, Rossant J, Gramolini AO, S. Adamson SL, & Kislinger T. Translational analysis of mouse and human placental protein and mRNA reveals distinct molecular pathologies in human preeclampsia. Mol Cell Proteomics 2011 Dec; 10(12): M111.012526
9. Cox B, Kotlyar M, Evangelou A, Ignatchenko V, Ignatchenko A, Whiteley K, Jurisica I, Adamson SL, Rossant J & Kislinger T. Comparative systems biology of human and mouse as a tool to guide the modeling of human placental pathology. Molecular Systems Biology 2009; 5: 279
- Javier Alfaro (co-supervised with Paul Boutros)
- Ankit Sinha