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Dr. Robert Gerszten

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!

 

Comments

Name
Joseph Nashed

Tue, 09/24/2019 - 11:33

I thought Dr. Gerszten's talk was really interesting, and although I am just being introduced to the field of metabolomics, one of the things that really stood out to me from Dr. Gerszten's talk was how metabolomics and proteomics could be used in personalized medicine - specifically predict the future development of this diseases like DM and CVD. Dr. Gerszten emphasized the importance of these tools and how they could be used to place people in prognostic categories, which could eventually lead to more specific treatment plans and interventions. In our discussion, Dr. Gerszten easily convinced me of the importance of one day having metabolomic and proteomic profiles similar to the human genome project, and how valuable that would be in medicine.

Thank you again Dr. Gerszten!

Name
Joseph Nashed

Yes this stood out to me as well! Will be interesting to see how these types of technologies become incorporated into everyday clinical practise.

One thing that Dr. Gerszten mentioned in his publication, "Application of Metabolomics to Cardiovascular Biomarker and Pathway Discovery," was the idea of pattern recognition analysis. In practise, this means recognizing a pattern of peaks without necessarily knowing the underlying metabolites, and comparing this pattern with patterns known to represent disease states. A limitation of this type of analysis is that there isn't enough data yet to define the baseline pattern of a healthy individual versus someone living with CVD or DM, for example.

If metabolomics and proteomics do eventually become a part of your routine checkup, I could see that baseline quickly becoming established and the power of this type of pattern recognition could make it a common diagnostic protocol!

Name
Austin Read

Name
Madison MacKinnon

Tue, 09/24/2019 - 11:43

I found our discussion with Dr. Gerszten on the publics tendency to distort the impact of research findings to be very pertinent and echoed what we talked about in a previous TMED class of ours. We previously discussed the "War on Cancer" in the 1970's and the disillusionment the public felt from the lack of cure or visible effect of the research. This caused a translational gap of knowledge between the public and scientists , with communication between the two being the main factor. Therefore, I commend Dr. Gerszten for raising this point and having this discussion in-depth with us to address these issues. Hopefully, we can all take steps to prevent situations like this from happening in the future, and promote communication and knowledge between scientists and the public.

Thank you Dr. Gerszten for your time and for your incredibly interesting talk!

Name
Madison MacKinnon

Name
Sophia Linton

Thu, 09/26/2019 - 09:12

In reply to by Madison MacKinnon (not verified)

Great point Madison. Antibiotics and the Golden Age of Medicine also afford a similar example!

Name
Sophia Linton

Name
Quentin Tsang

Tue, 09/24/2019 - 13:23

During Grand Rounds, Dr. Gerszten touches on cardiorespiratory fitness and cardiovascular disease and this stuck with me most throughout his lecture and our post-rounds discussion. Perhaps I am biased, coming from a kinesiology background, but I think the most compelling data presented in Dr. Gerszten's presentation was the ability of cardiorespiratory fitness to be a strong, independent marker of cardiovascular health as well as morbidity and mortality. The improvement of 1 MET unit (a measure of cardiorespiratory fitness) is able to reduce all-cause morbidity and mortality in adults by 15-17%! As Dr. Gerszten is extremely interested in metabolomics, I am extremely interested to see if there is a changed metabolomic profile in those with low vs. high CRF.

I also believe that this grand rounds lecture reminds us that health sciences research and knowledge translation is interdisciplinary in nature and requires collaboration from all health professions, not just physicians. Dr. Robert Ross (who happened to be my undergraduate thesis supervisor) is a faculty member in the School of Kinesiology and Health Studies and a Registered Kinesiologist. His collaboration with Dr. Gerszten brings new perspective about cardiovascular health that a physician may not have. Furthermore, he brings new insight that will allow novel treatment methods to be brought from bench to bedside. This is an excellent example that demonstrates that translational medicine requires the collaboration of all key stakeholders in order to be effective and improve patient outcomes.

Name
Quentin Tsang

I would agree, and it does seem likely that metabolomic and proteomic analysis is translatable across a variety of disciplines in medicine.

In relation to your research interest, it would be interesting seeing how these types of analytical techniques may elucidate key differences in circulating metabolites and expressed proteins in those with low vs high CRF.

Name
Austin Read

Name
Sophia Linton

Tue, 09/24/2019 - 16:14

Thank you, Dr. Gerszten, for a fantastic post-rounds discussion. Thank you, Austin, for a well-written summary of the presentation and our talk.

Metabolomics studies have produced significant breakthroughs in biomarker discovery and the identification of novel metabolites. However, many factors have hindered translation of the research outcomes into clinical tests and user-friendly interfaces.
One limitation of metabolomics discussed in our talk was the lack of information in the databases. In an untargeted analysis, for example, only 10-20 percent of the readout is identifiable through databases and other searches. More research is needed to identify the additional 80-90 percent not to mention their potential as biomarkers for disease.

One could argue, the current field of metabolomics affords an excellent example of the reality of translational research - it's a long journey from lab to clinic.

Name
Sophia Linton

I couldn’t have said it better myself, Sophia! A major take-away I got from Dr. Gerszten’s presentation was that yes, there is huge potential for ground-breaking discoveries within these transient molecules, but how realistic is it to actually pinpoint exactly which ones are pathologically important in addition to variability in testing populations? It may be a little naïve for me to say that our post-discussion gave me a rather chilling awakening regarding the complexity of diseases, but as an old colleague of mine used to say, “If it isn’t hard, someone would’ve done it already!”

It was a pleasure to hear Dr. Gerszten speak and well written Austin!

Name
Thalia Hua

Name
Daniel Rivera

Tue, 09/24/2019 - 19:09

Doing research in a field quite different from cardiovascular metabolomics, I was unsure of what I may take away from Dr. Gerszten's Grand Rounds presentation. After his engaging presentation and the following small group discussion, I can say I am leaning towards the stance that metabolomics may be be the next big thing in biomedical science, leaving me more convinced about its potential applications in a variety of fields. An interesting discussion took place between Dr. Gerszten and a fellow student and member of the research unit I am based out of, discussing the potential application of metabolomics in predicting risk of IBS or IBD. Dr. Gerszten was cautious about asserting that the work already done via metabolomics and such a disease/disease models would hold up, but shed light on various challenges the field must overcome (controlling for various experimental variables) in order improve reproducibility of such metabolomic experiments. Despite his caution, his comments were encouraging and suggested that meaningful application of metabolomics in such a field can be achieved.

As the scientific community, researchers and funding agencies alike, begin to reinvigorate their interest in the applications of metabolomics in the study of various diseases (as Dr. Gerszten had suggested is already taking place), I believe metabolomics will come to be an important clinical diagnostic and prognostic tool. We're not quite yet there - there are obstacles that must be overcome in a number of fields and perhaps with the technology itself - but Dr. Gerszten's presentation and the work he presented have made be a believer that we may just be on the precipice of a breakthrough that will radiate clinical and basic science specialties/fields. Dr. Gerszten compared the metabolomics/proteomics movement to the Human Genome Project (HGP). Like the HGP, I hope collaboration and public and scientific interest drive further exploration of metabolomics such that it may, if it holds up, revolutionize clinical practice.

It was a pleasure to attend this Grand Rounds - thank you, Dr. Gerszten!

Name
Daniel Rivera

You're right Daniel, it does seem like there are quite a few barriers which may impact our ability to apply these types of technologies in everyday medicine. Will be interesting to see how soon these types of techniques become common in clinics, and if any major breakthroughs in these types of instruments may be first required.

Name
Austin Read

Name
Edwin Ocran

Tue, 09/24/2019 - 23:04

Thank you Dr. Gerszten for the great presentation and for having a more in-depth discussion about your research with us during the post-round group session. One of the things I found interesting was how metabolomics could potentially predict the development of conditions like cardiovascular disease in individuals who would have otherwise been overlooked based on traditional risk factors and testing such as age, smoking, high blood pressure, and high cholesterol. This is a very promising field and I am eager to see the advancement it brings to clinical care in the near future.

Name
Edwin Ocran

Name
Marty VandenBroek

Wed, 09/25/2019 - 07:40

Dr. Gerszten's presentation and discussion with our class was a great reminder about how science and medicine are so tightly intertwined, and how advancements in one field can have drastic impacts on another. The improvement in sensitivity and efficiency of mass spectrometry has incredible implications for the potential to bring a more personalized treatment to patients that could reveal aspects of their conditions that we may have never imagined before this technology. I found it striking how such a minute portion of a patients blood sample after it is processed to be usable in mass spec can reveal so many correlated factors to the development of disease. I can only imagine how much the technology may be able to advance to learn even more about a wide variety of diseases. The future of treatments looks very promising with people like Dr. Gerszten pushing the boundaries of our current knowledge!

Name
Marty VandenBroek

Great take away points Marty. The interaction particularly between the analytical chemistry field and the medical sciences is crucial to improving diagnostic methods. However, I think that the complexity of these technologies, particularly the new advances in mass spectrometry that Dr. Gerszten described in his Grand Rounds talk, and the unfamiliarity that many health care practitioners may have with these technologies could present a barrier to widespread clinical implementation. If implemented in a clinic, not only would there need to be someone who is able to successfully perform the mass spec, but there would also need to be established guidelines for how to integrate the results of this test into the diagnostic process. I agree with your assessment that this technology has the potential for many fascinating improvements in medicine, but I'm curious what you think about these barriers to implementation. Thanks again for your post!

Name
Matthew James

Name
Reem Alzafiri

Wed, 09/25/2019 - 19:35

Dr. Gerszten's MGR presentation and discussion with our class has given me much insight on the new technologies that will help us discover new biomarkers, proteomics, and metabolomic that could give rise to potential disease pathways thanks to translational research. These discoveries open doors to novel mechanisms, that have not been properly established before, can further lead us to potential therapeutic advances. For instance, Dr. Gerszten's group's discovery of the correlation of key amino acids and diabetes has led to further findings in regards to the underlying mechanism of diabetes which could potentially lead to novel therapies in the future. What I took from this presentation is that the impact of proteomics and metabolomics on biomedical research is not only relevant to disease states but is of most importance for novel discovery of mechanism pathways and potential therapeutics.

Name
Reem Alzafiri

Name
Jay Kataria

Sat, 09/28/2019 - 17:28

The discussion with Dr. Gerszten after Medical Grand Rounds last week was a fantastic experience. Dr. Gerszten discussed how a few protein markers have been approved for the diagnosis or screening of cardiovascular diseases. He mentioned how metabolomics and proteomics in personalized medicine have the potential to provide screening biomarkers and to elucidate biological pathways underlying disease states. This presentation was particularly interesting as he mentioned controversies and obstacles surrounding emerging techniques in this field - high variability amongst global populations and individuals with CVD fall into into different conventional high-risk groups.
The idea that proteomics may generate multiple novel biomarkers along new pathways to help improve diagnosis is very exciting.
In addition, it was great to emerge in a thoughtful discussion with Dr. Gerszten and Austin. In particular, discussing how prescribing patients to engage in cardiorespiratory fitness gave me a new perspective on how clinicians may treat patients. Finally, it was great to end with what his thoughts are on the US healthcare system and the obstacles surrounding it.

Thank you Dr. Gerszten for discussing your research with us. Thank you Austin for facilitating this discussion.

Name
Jay Kataria

Name
Jay Kataria

Sat, 09/28/2019 - 17:32

The discussion with Dr. Gerszten after Medical Grand Rounds last week was a fantastic experience. Dr. Gerszten discussed how a few protein markers have been approved for the diagnosis or screening of cardiovascular diseases. He mentioned how metabolomics and proteomics in personalized medicine have the potential to provide screening biomarkers and to elucidate biological pathways underlying disease states. This presentation was particularly interesting as he mentioned controversies and obstacles surrounding emerging techniques in this field - high variability amongst global populations and individuals with CVD fall into into different conventional high-risk groups.
The idea that proteomics may generate multiple novel biomarkers along new pathways to help improve diagnosis is very exciting.

In addition, it was great to emerge in a thoughtful discussion with Dr. Gerszten and Austin. In particular, discussing how prescribing patients to engage in cardiorespiratory fitness gave me a new perspective on how clinicians may treat patients. Finally, it was great to end with what his thoughts are on the US healthcare system and the obstacles surrounding it.

Thank you Dr. Gerszten for discussing your research with us. Thank you Austin for facilitating this discussion.

Name
Jay Kataria

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