Holger Alexander Ebhardt
Theme: using proteomics (LC-MS/MS) to address critical questions in cancer biology Keywords: - proteomics (MALDI, ESI, LC-MS/MS) - systems biology - computational data analysis Prostate cancer: - why is it important to develop higher order drug combinations (Root et al. https://doi.org/10.1002/pros.23694 ) - how systems pharmacology and proteomics lead to new insight into disease progression (Ebhardt et al. https://doi.org/10.1038/s41540-018-0064-1 ) - testing of new therapy lead (Root et al. https://doi.org/10.1186/s12943-018-0905-y ) Cancer cachexia: - part of the puzzle on physiological changes of skeletal muscles in cancer cachexia (Ebhardt et al. https://doi.org/10.1002/jcsm.12188 ) - more research is needed to understand this complex disease. Detailed background: H. Alexander Ebhardt obtained his Ph.D. in Molecular Biology and Biochemistry from Simon Fraser University, B.C., Canada investigating endogenous and exogenous small RNAs in a virally infected system (PNAS 2005). While annotating DNA sequencing data, he noticed that not all small RNA sequences perfectly match to their genome of origin. Further investigation into this peculiar phenomena revealed, that these 'sequencing errors' often coincide with post-transcriptional modifications of the RNA base (NAR 2009) and can impact argonate effector complex association of small RNAs (Silence 2010).During a RiboClub meeting in Sherbrook, Q.C., Canada a question was posed to the audience: How did the RNA World end? Alex hypothesized: With the arrival of RNase A. This in turn underlined the importance of not only studying RNA, but also proteins. Hence, he expanded his expertise to quantitative mass spectrometry and developed a method to rapidly quantify kinetics of conjugating single amino acids to proteins using MALDI (Anal Chem 2009). Depending on the conjugated amino acid, this post-translational modification can also improve fragmentation of peptides in LC-ESI-MS/MS (RCMS 2014). As protein networks are comprised of multiple protein entities, Alex used targeted proteomics (or selected reaction monitoring SRM-MS) to quantify proteins in undepleted human cell lysates (Proteomics 2012). Currently most SRM-MS publications are linked to clinical studies (Proteomics 2015) while the proteomics research community is moving towards SWATH-MS (Sci Data. 2014). Using SWATH-MS, Alex quantified various biological systems and is in the process of publishing the results. His research group at SBI focuses on addressing fundamental questions in biochemistry and unmet clinical needs using targeted proteomics (LC-ESI-MS/MS). His latest research findings were submitted to the EAU17 (European Association of Urology annual congress) and the thematic session highlighted in the daily conference news and in URO TODAY.
- PhDSimon Fraser University BC