Novel technologies for cardiovascular biomarker discover: from a Chem 20 to a Chem 2000
Austin Read, MSc Candidate, Translational Medicine
At the Medical Grand Rounds this past week, Queens University had the pleasure of hosting Dr. Robert Gerszten, a Professor of Medicine at Harvard Medical School and the Director of Clinical and Translational Research for the MGH Heart Center. Dr. Gerszten’s presentation focused on the increasing role of metabolomics and proteomics in personalized medicine, and their potential to provide novel screening biomarkers and elucidate biological pathways underlying disease states.
As he mentioned in our post-round discussion, Dr. Gerszten became quickly aware of the gaps in available biomarkers for predicting and diagnosing cardiovascular disease once he began practising clinical cardiology. Despite the usefulness of traditional risk factors for developing cardiovascular disease (CVD), such as age, gender, elevated blood pressure, diabetes and smoking, not all individuals diagnosed with CVD fall into the conventional high-risk groups.
In the field of cardiology, genome-wide analysis has allowed for the identification of high-risk populations for CVD, however these methods suffer from poor resolving power and high variability amongst global populations. Novel high-throughput technologies, based on an individual’s circulating metabolites (metabolomics) and expressed proteins (proteomics), provide clinicians additional information which may prove useful in identifying novel disease biomarkers.
The applicability of these new technologies is evident in Dr. Gerszten’s work looking at metabolites and the development of diabetes mellitus (DM). Through metabolomic analysis, five amino acids have been found to be associated with risk of future diabetes. The prevalence of these amino acids in populations at risk of developing DM may imply that baseline metabolite measurements could predict the future development of this disease in high risk-populations. In addition, baseline levels of a specific type of cholesterol (C 18:2) was found to predict the greatest reduction in DM risk with lifestyle treatment.
Collectively, this demonstrates how metabolomics can predict future development of DM in high-risk populations, and can also predict risk for developing DM based on preventative treatment received. Although further validation is required, this work suggests that metabolite biomarkers have the potential of influencing clinical decisions and offering more personalized preventative strategies.
In addition to their potential to discover novel disease biomarkers, proteomic and metabolomic analysis may provide insight into biological pathways underlying disease. By identifying these mechanisms, this may lead to the discovery of novel metabolite receptors and proteins as potential therapeutic targets. The discovery of the correlation of certain amino acids and diabetes by Dr. Gerszten’s group has led to further work elucidating the role of an activator for an enzyme involved in the catabolism of those same metabolites. This type of information regarding the underlying mechanism of DM may led to novel therapies targeting this activator or enzyme, illustrating the impact that proteomics and metabolomics may have on biomedical research.
Both metabolomic and proteomic analysis rely on sophisticated instruments in order to accomplish the required separation of complex biological samples. In our discussion, Dr. Gerszten shared his opinions on the logistics of implementing these types of devices in clinical settings and shared what he felt were the most important barriers that needed to be overcome before these types of analysis are common place. Beyond the technical issues which may arise when dealing with these types of sophisticated equipment, Dr. Gerszten felt a larger barrier may be convincing clinicians of their practicality and applicability in everyday clinical scenarios.
Dr. Gerszten also shared his opinion on the media’s perception of research in the field of medicine, and the tendency of the public to overexaggerate the impact of novel research findings. As he mentioned in his Grand Rounds presentation, an article published by the New York Times, titled “Proteomics might have saved my mother’s life. And it may yet save mine,” was written to illustrate the novelty of proteomic screening markers. Based on his discussion with the author of the article, Dr. Gerszten shared how he believed clinicians may not be hesitant enough when prescribing medical interventions based on novel screening biomarkers, and how patients may be too accepting of these treatments.
On behalf of the Department of Medicine and Queens University, thank you Dr. Gerszten for sharing some of your work and thoughts on the growing field of personalized medicine!