Research Discipline(s): Basic, Translational
Primary Title: Professor, Department of Internal Medicine
Additional Titles & Affiliations: Director, Manitoba Centre for Proteomics and Systems Biology
RESEARCH TOPICS
Blood Disorders, Proteomics, Proteogenomics, Assay Development
University of Manitoba
715 McDermot Ave, 799 John Buhler Research Centre
Winnipeg, MB R3E 3P4
Canada
Protein mass spectrometry is a key technology not only to identify markers of disease and drug response but, moreover, to detect these markers in patient samples for improving precision medicine and consequently patient outcomes.
Research Summary
A major focus of my research program is developing novel and improved methods for the quantitative analysis of protein expression and post-translational modifications (PTMs) such as phosphorylation, nitrosylation, or proteolytic cleavage, in clinical samples using state-of-the-art protein mass spectrometry (MS). We have previously used MS to study signaling in different cancers, leading for instance to the identification of MARCKS as a marker of response to BTK inhibitors in chronic lymphocytic leukemia patients (Beckmann et al, Blood 2020). We have established robust workflows to analyze the proteome of fresh frozen and formalin-fixed paraffin-embedded tissue samples, using minimum sample input (e.g., 3-µm slides or <1 mm3 cores), and we have used these methods for the proteogenomic analysis of colorectal cancer metastases. To analyze the more and more complex multi-omics datasets, we are increasingly making use of artificial intelligence and machine learning approaches.
Goals
Using state-of-the-art protein mass spectrometry methods, my goal is to make precision medicine more precise by detecting prognostic and predictive markers of disease as well as potentially novel vulnerabilities in individual patients.
Research Biography
I received my master's degree in biochemistry from the University of Bochum/Germany in 2004 and my PhD in Chemistry from the University of Wuerzburg/Germany in 2008. After two years as a postdoctoral fellow at the Leibniz-Institute for Analytical Sciences (ISAS) in Germany, I became an independent junior principal investigator for Signaling Proteomics in 2014 and a permanent senior principal investigator for Protein Dynamics in 2014.
In 2018, I became Associate Director of the Segal Cancer Proteomics Centre at the Jewish General Hospital in Montreal and an associated member of McGill’s Centre for Translational Research in Cancer. In 2022, I joined the University of Manitoba’s department of internal medicine and became Director of the Manitoba Centre for Proteomics and Systems Biology.
I have published >150 peer-reviewed scientific articles, including pioneering work on using quantitative proteomics of human platelets and studied the dynamics of platelet activation and inhibition through temporal phosphoproteomics. I have developed novel and improved methods for the sensitive analysis of post-translational modifications (PTMs) such as protein phosphorylation, proteolytic cleavage, and redox modifications, as well as the combination thereof to study PTM-crosstalk.
In 2021 I was elected as member of the board of the Canadian National Proteomics Network (CNPN).
Achievements
- List coming soon
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Featured Publications
- Mitsa G, Guo Q, Goncalves C, Preston SEJ, Lacasse V, Aguilar-Mahecha A, Benlimame N, Basik M, Spatz A, Batist G, Miller WH Jr, Del Rincon SV, Zahedi RP*, Borchers CH*. A Non-Hazardous Deparaffinization Protocol Enables Quantitative Proteomics of Core Needle Biopsy-Sized Formalin-Fixed and Paraffin-Embedded (FFPE) Tissue Specimens. Int J Mol Sci. 2022 Apr 18;23(8):4443. doi: 10.3390/ijms23084443. PMID: 35457260; PMCID: PMC9031572.
- Beckmann L, Berg V, Dickhut C, Sun C, Merkel O, Bloehdorn J, Robrecht S, Seifert M, da Palma Guerreiro A, Claasen J, Loroch S, Oliverio M, Underbayev C, Vaughn L, Thomalla D, Hülsemann MF, Tausch E, Fischer K, Fink AM, Eichhorst B, Sickmann A, Wendtner CM, Stilgenbauer S, Hallek M, Wiestner A, Zahedi RP*, Frenzel LP*. MARCKS affects cell motility and response to BTK inhibitors in CLL. Blood. 2021 Aug 19;138(7):544-556. doi: 10.1182/blood.2020009165. PMID: 33735912; PMCID: PMC8377477.
- Ibrahim S, Lan C, Chabot C, Mitsa G, Buchanan M, Aguilar-Mahecha A, Elchebly M, Poetz O, Spatz A, Basik M, Batist G, Zahedi RP*, Borchers CH*. Precise Quantitation of PTEN by Immuno-MRM: A Tool To Resolve the Breast Cancer Biomarker Controversy. Anal Chem. 2021 Aug 10;93(31):10816-10824. doi: 10.1021/acs.analchem.1c00975. Epub 2021 Jul 29. PMID: 34324311.
- Mnatsakanyan R, Markoutsa S, Walbrunn K, Roos A, Verhelst SHL, Zahedi RP. Proteome-wide detection of S-nitrosylation targets and motifs using bioorthogonal cleavable-linker-based enrichment and switch technique. Nat Commun. 2019 May 16;10(1):2195. doi: 10.1038/s41467-019-10182-4. PMID: 31097712; PMCID: PMC6522481.
- Shema G, Nguyen MTN, Solari FA, Loroch S, Venne AS, Kollipara L, Sickmann A, Verhelst SHL, Zahedi RP. Simple, scalable, and ultrasensitive tip-based identification of protease substrates. Mol Cell Proteomics. 2018 Apr;17(4):826-834. doi: 10.1074/mcp.TIR117.000302. Epub 2018 Jan 22. PMID: 29358340; PMCID: PMC5880100.
- Plenker D, Riedel M, Brägelmann J, Dammert MA, Chauhan R, Knowles PP, Lorenz C, Keul M, Bührmann M, Pagel O, Tischler V, Scheel AH, Schütte D, Song Y, Stark J, Mrugalla F, Alber Y, Richters A, Engel J, Leenders F, Heuckmann JM, Wolf J, Diebold J, Pall G, Peifer M, Aerts M, Gevaert K, Zahedi RP, Buettner R, Shokat KM, McDonald NQ, Kast SM, Gautschi O, Thomas RK, Sos ML. Drugging the catalytically inactive state of RET kinase in RET-rearranged tumors. Sci Transl Med. 2017 Jun 14;9(394):eaah6144. doi: 10.1126/scitranslmed.aah6144. PMID: 28615362; PMCID: PMC5805089.
- Beck F, Geiger J, Gambaryan S, Solari FA, Dell'Aica M, Loroch S, Mattheij NJ, Mindukshev I, Pötz O, Jurk K, Burkhart JM, Fufezan C, Heemskerk JW, Walter U, Zahedi RP*, Sickmann A*. Temporal quantitative phosphoproteomics of ADP stimulation reveals novel central nodes in platelet activation and inhibition. Blood. 2017 Jan 12;129(2):e1-e12. doi: 10.1182/blood-2016-05-714048. Epub 2016 Nov 9. PMID: 28060719; PMCID: PMC5248936.
- Gonczarowska-Jorge H, Loroch S, Dell'Aica M, Sickmann A, Roos A, Zahedi RP. Quantifying Missing (Phospho)Proteome Regions with the Broad-Specificity Protease Subtilisin. Anal Chem. 2017 Dec 19;89(24):13137-13145. doi: 10.1021/acs.analchem.7b02395. Epub 2017 Nov 28. PMID: 29136377.
