A surgeon and a statistician: Derek Klarin looks to combat cardiovascular disease on multiple fronts

Derek Klarin knows what it’s like to operate on patients with advanced cardiovascular disease. And like any good doctor, he wishes it never had to come to that. That’s why he’s also a researcher, working to uncover biological insights that might prevent cardiovascular disease from developing in the first place.

As a statistical geneticist finishing up his postdoctoral fellowship under Sek Kathiresan at Broad and at Massachusetts General Hospital (MGH), where he is a surgical resident, Klarin mines troves of genetic data from electronic health record collections from such sources as the Million Veteran Program and the UK BioBank in an effort to better understand how genes contribute to heart disease and other conditions of interest to vascular surgeons. Such insights may not only suggest who is at greater risk of developing disease, but might also reveal how these conditions work, possibly pointing to more effective treatments.

In a #WhyIScience Q&A, Klarin discusses the importance of biobanks to his work, and explains how his unusual perspective as a surgeon-scientist informs his research.

Q: Can you describe the work that you do at Broad and MGH?
A: In terms of my research interests, I study the genetics that underlie cardiovascular disease. This includes investigating the genes that cause these conditions, as well as the genes that influence risk factors linked to these diseases, such as blood lipid levels and cholesterol. Our team uses large datasets of genetic and health information to uncover associations between these genes, diseases, and risk factors with the hope that understanding those connections can help identify new treatments for patients.

Q: You’re also a general surgery resident. What is it like to balance research and clinical duties?
A: I am currently a chief resident in general surgery at MGH and, after completing my residency this year, I plan to pursue subspecialty training in vascular surgery. I enjoy balancing the demands of clinical surgical care and the intellectual rigor of research. In many ways the two roles complement each other. When I encounter an interesting clinical problem or question, it often spurs a new research idea or project. I also believe that surgeons think about medicine differently than other specialties, and we can provide unique insight into challenging clinical and research problems. Surgeons see the direct effects of disease on the human body every day in the operating room.

Derek Klarin intends to pursue subspecialty training in vascular surgery, and continue his genetics research, after completing his residency later this year.

Q: What, in your opinion, has been your biggest scientific accomplishment to date?
A: Over the past two years, I was fortunate enough to lead one of the first major projects from the Million Veteran Program. In the project, which was recently published in Nature Genetics, we identify genetic mutations that appear to improve lipid and cholesterol levels and may protect against heart disease. There is one protective mutation in particular that was exciting because there is already a drug on the market, called cilostazol, that mimics its effects. Since it has already been through clinical safety trials, we hope that it could be used to help prevent heart disease without the high cost and long development timelines usually seen for new pharmaceuticals.

Q: In your recent paper, you relied on data from the Million Veteran Program. What does a dataset like that reveal that other datasets might not?
A: The Million Veteran Program (MVP) was established in 2011 by the Veteran Affairs (VA) Office of Research and Development as a nationwide research program within the VA healthcare system. The goal of MVP is to enroll one million veterans with the expectation that this data will reveal new biologic insights and discoveries and enhance the care of U.S. veterans through precision medicine. The dataset is unique in that it allows us to first and foremost provide a way to give back to the many veterans, like my own grandfather, who have proudly served our country.

Q: Are there health issues specific to veterans that the data can help address?
A: There are some health issues that are specific to the veteran population, or at least more common among veterans. Veterans are at higher risk for heart disease than the general population, for instance, and maybe datasets like MVP can help us understand why. The large scale of participation in MVP has resulted in this tremendous resource that will allow researchers to study and learn about certain diseases and syndromes that may be understudied or underrepresented in the general population but have a large effect on veterans’ health. Their participation in this study allows us to find new information that we hope can immediately improve their health and well-being.

Q: What’s next for your research?
A: I plan to continue working with the Million Veteran Program dataset while undergoing my subspecialty training in vascular surgery. To date I have focused primarily on lipids and cholesterol, but our next project involves looking more specifically at cardiovascular diseases with higher prevalence in veterans including stroke and peripheral artery disease. We hope this work can help facilitate the development of new treatments to prevent or reduce the need for more invasive therapy later in a patient’s lifetime.