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Translational Mass Spectrometry in Clinical Chemistry

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Translational Mass Spectrometry in Clinical Chemistry Expert opinion About us needs, analytical chemists support us with the assay development The clinical chemistry lab at the Leiden University Medical Center (LUMC) for molecular phenotyping of disease and health using MS-based works closely together with researchers at the Center for Metabolomics technology. Together we attempt to bring promising biomarkers and Proteomics (CPM) to develop new bioanalytical tests. The goal from the research field into the clinical arena. We believe that this is to contribute to Precision Medicine through improved, molecular collaboration should lead to a more robust and effective pipeline for characterization of health and disease, for the sake of better patient developing medical tests. We also support research from various clinical management and patient outcome. groups at the LUMC, especially in the domains of Cardiovascular Diseases, Cancer Diagnosis and Kidney Diseases.” Christa Cobbaert heads the Department of Clinical Chemistry and Laboratory Medicine at LUMC, which encompasses clinical chemistry, hematology, coagulation and blood transfusion. Improving effectiveness Van der Burgt: “One of the main activities at CPM is the elucidation “In addition to regular patient diagnostics, our department also has of modifications on existing protein biomarkers, with emphasis on responsibility for the hospital-wide central receipt of patient and glycosylation analysis. As we want to make sure that these biomarkers research specimens. Our department supports research and biobanking can be of use for the clinic, we do not only report discoveries, but from a large variety of clinical groups that want to use our services. rather aim for further development of our findings into something Another core task is training and education of lab specialists and clinically useful. Therefore we first make an inventory of the unmet medical technicians. needs from the clinicians, and what is actually needed for improved patient care. Hence, the clinical need guides our -omics research. And “Some current numbers? Our routine lab works 24/7, we do about it is my task to bring these two worlds together. My goal is not just to 4000 specimens per day, and produce over 4 million tests per year. publish papers on new discoveries, but to contribute to finding more We have 180 employees, about 140 full time equivalents. The majority effective solutions: clinically effective, cost effective and safe tests are phlebotomists, who collect blood, and medical technologists, who for patient care.” Translational run the analyses. We have an academic staff encompassing multiple laboratory specialists, who are responsible for the lab policy, lab Cobbaert: “The current pipeline and the current process of financing organization, for state-of-the-art test menus, clinical consulting and research is in my perception a wasteful process because there is post-academic training of lab specialists. Head medical technicians, insufficient attention to the downstream consequences (utility) of mass spectrometry in quality control officers, as well as information and communication the research findings for patient care. Currently the number of papers technology specialists and administrative personnel are a coaching and citation indices are rewarded, rather than the impact for patient layer between the academics and the operational co-workers. care. Subsidizers should stimulate the translation and implementation of newly discovered biomarkers by making the funding of translation clinical chemistry “Since we are an academic institute, we are responsible for the and implementation research inclusive. traineeship of new lab specialists. We also contribute to the education of medical doctors. Teaching future medical doctors about the targeted “To counteract this inefficient pipeline from discovery to application use of lab diagnostics is key because approximately 70% of medical researchers, clinicians, biostatisticians and lab specialists should decisions in hospitals are based on lab results. We further provide collaborate closely. The clinical needs should be the driver of the Professor Cobbaert heads the Department of Clinical Chemistry and Laboratory Medicine at Leiden University Medical Center (LUMC), Leiden, The Netherlands teaching contributions in new disciplines such as clinical technology, test development process, rather than the technological push. and contribute to different Masters programmes.” Once these needs are identified a more informed decision can be made with regard to priorities: ‘This is what we are setting up Expert opinions from Prof. Christa Cobbaert and Dr Yuri van der Burgt Dr Yuri van der Burgt is an associate professor at the CPM. “Trained as a together and this is where we go for’. The European Federation of chemist, I did a PhD in bioorganic chemistry and moved to the clinical Laboratory Medicine (EFLM) Test Evaluation framework provides field. At the LUMC I joined pioneering ‘omics’ research for medical guidance and encompasses key elements for creating evidence Current mass-spectrometry-based strategies will allow us to understand the molecular care and patient research. For 50% of my time I work for the clinical regarding the clinical and cost-effectiveness of new medical tests. chemistry lab, and from that position I bridge to the CPM research phenotypes of disease, which will drastically improve the diagnostic power of new aiming for improved biomarker translation. CPM has approximately “Our mantra is that our re- clinical tests. In this interview, Professor Cobbaert [head of the Department of 50 researchers (PhD students postdocs, senior scientists, assistants search efforts should lead to and associates) and is headed by Manfred Wuhrer. We explore promising precision diagnostics and clini- Clinical Chemistry and Laboratory Medicine at the Leiden University Medical Center biomarkers that are discovered in basic research and aim to verify their cally effective medical tests. (LUMC), Leiden, The Netherlands] and Dr Van der Burgt (associate professor at the potential for translation to the clinic. Mass-spectrometry (MS)-based In our collaboration with CPM omics studies have reported a wide variety of biomarkers or signatures, we aim to contribute to better Center for Proteomics and Metabolomics, LUMC) give us their expert opinions on but only a few of these have been translated into a laboratory test. patient management and how a strong collaboration between biomarker researchers, clinicians and medical This limited translation is partly due to the lack of standardized patient outcome with a protocols, robustness and reproducibility, but more importantly targeted approach. As it is laboratory specialists is necessary to make the development process more efficient. ill-defined or flawed study designs.” essential to add value to Professor Cobbaert is driven to innovate the field of laboratory medicine: “The clinical clinical pathways and patient Cobbaert: “We are happy with the cooperation with CPM because management, we need lab will change from a care-relevant to a system-relevant cross-sectoral discipline which it’s very important to have analytical chemists connected to our lab. actionable results for will greatly affect the development of the entire healthcare system”. Once that lab specialists and clinicians have identified unmet clinical better patient care.” Samples ready for the mass spectrometer | 22 February/March 2020 23 | Expert opinion International initiatives Collaboration is key Cobbaert: “We try to educate stakeholders of the biomarkers-medical Van der Burgt: “An example of such a collaboration between CPM test pipeline about the usefulness of the Test Evaluation framework and clinical chemistry is our work on glycoprotein markers that we for guiding this development process. recently presented at the symposium on precision diagnostics, ‘Prime Dr van der Burgt is an associate time for precision diagnostics driven by unmet clinical needs’ professor at the Center for Proteomics “We have asked ourselves: Why is the process from research to appli- (LUMC, Leiden, The Netherlands, November 2019). and Metabolomics, LUMC, Leiden, The Netherlands cation such a wasteful process? What should we do? Last November we organized a precision diagnostics symposium in which we shared “Structure refinement of the biomarker for prostate cancer, the our experiences on quantitative proteomics and proposed our solutions prostate specific antigen (PSA) demonstrated the importance of glyco- The experts [‘Prime time for precision diagnostics driven by unmet clinical needs’ sylation for further development. We have worked on PSA at the CPM Professor Christa Cobbaert PhD, EuSpLM (LUMC, Leiden, The Netherlands, November 2019)]. We also shared together with the clinical chemistry lab and in that collaborative effort Department of Clinical Chemistry and Laboratory Medicine, our struggles: developing specific molecular tests for proteins is not we have seen that we can add extra information on the PSA test Leiden University Medical Center, Leiden, The Netherlands an easy road. Several barriers had to be alleviated. And that’s difficult readout. Additionally, we aim to discover novel biomarkers for early www.universiteitleiden.nl/en/staffmembers/christa-cobbaert#tab-1 to do, sometimes we failed, sometimes we felt that it doesn’t go quick detection of cancers. We see an enormous worldwide effort there enough. But we all are dedicated to make it a success together. and the result is hundreds, if not thousands, of new markers without
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