Interview with Dr. Prashant Rao on Advancing Heart Health Through Exercise
Prashant Rao, MD, is a cardiologist at Beth Israel Deaconess Medical Center (BIDMC) whose work bridges clinical practice and leading-edge research on the genetic and molecular mechanisms underlying the body's response to exercise. As an investigator in BIDMC's Program in Personal Genomics and Cardiometabolic Disease, led by Dr. Robert Gerszten, Dr. Rao and colleagues leverage advanced technologies to map the complex biological shifts that occur during physical activity with the goal of uncovering novel cardiovascular biomarkers, identify promising drug targets, and develop "exercise mimetics"—therapies designed to replicate the benefits of exercise and help individuals improve exercise performance.
Ultimately, Dr. Rao seeks to answer the question, "Why does exercise benefit some people more than others?" We asked Dr. Rao about what he's learned so far.
Question: What is your research focus and what is it about this field that really drives your curiosity? What's the big question that keeps you going?
Prashant Rao: I work primarily within Dr. Robert Gerszten's lab, where we focus on the biochemical profiling of exercise. The goal is to identify new biomarkers for cardiovascular disease, as well as potential drug targets or "exercise mimetics"—therapies that mimic the benefits of exercise for people who can't exercise as easily.
On a personal level, it's because I exercise quite a lot and I'm always interested in understanding how exercise mediates a lot of the benefits that it does, and why is it that some people respond in really impressive ways and other people, not so much?
There must be some genetic component to this. You can take for example, my brother and I both run quite a bit, and we started running at pretty much the same time. But I hate to admit it, he's probably a lot better than I am, even though we started around the same time. I always wonder why it is that he's doing a little bit better whereas I'm not doing as well?
So, these are the kinds of personal things which I've experienced, but actually, it's important from a patient's standpoint. It would be great to understand which people are really going to respond to which types of exercise. We could tailor our interventions a lot better.
Question: Are you starting to see patterns or findings in your research that point to why people respond so differently to exercise?
Prashant Rao: Yes, definitely. We're in a fortunate position at BIDMC because Rob Gerszten's lab serves as the core chemical analysis site for a major NIH-funded multicenter trial called MoTrPAC—the Molecular Transducers of Physical Activity Consortium. It's designed to rigorously investigate what happens at a molecular level both during and after an acute bout of exercise, and then what happens after 12 weeks of exercise training.
What makes MoTrPAC so exciting is that it studies both endurance and resistance training as two separate arms of the trial, with a control group as well. We're collecting clinical metrics—things like blood pressure, VO₂ max (a measure of cardiorespiratory fitness), and muscle strength—and we're also taking blood samples and tissue biopsies before and after exercise to analyze molecular changes.
That gives us a comprehensive view of how the body responds, and how the different modalities affect these metrics. This is one of the first large-scale efforts that has really tried to answer these questions. Early data is starting to emerge, and we're expecting more in the next year or so.
In parallel, we've also been closely collaborating with investigators from the Heritage Family Study, which involved 20 weeks of endurance training, where participants got their plasma taken before and after exercise training. We've been using newer technologies like proteomics to identify blood-based biomarkers linked to fitness and training response. So, between these two studies, we're fortunate that we've been in this space using these unique cohorts and these novel technologies. We're poised to be at the forefront, leading a lot of these investigations.
Question: Can you explain proteomics in a way that someone at Thanksgiving dinner could understand?
Prashant Rao: I usually explain it like this: ten years ago, if we had a sample of your blood, we could measure maybe a handful of molecules—and it would take a lot of time. Now, we have high-throughput technologies that allow us to measure thousands of molecules quickly and efficiently. That gives us a much more detailed picture of what's happening in your body, especially in response to something like exercise.
So, for example, your baseline blood chemistry first thing in the morning is going to look very different after a workout. And those changes contain a ton of information. In fact, one of our recent studies found that your blood pressure response to exercise—even in healthy people in their 20s—can predict your cardiovascular risk 20 years later. That blew us away. It also got us thinking: what if we could identify a blood-based biomarker that reflects that same risk, without needing to put someone on a treadmill?
Acute exercise can be a powerful tool for identifying markers of future disease risk, and long-term training helps us discover potential drug targets that replicate the effects of exercise.
Question: The Boston Marathon is around the corner. When you watch 10,000 people of all shapes and sizes run down Commonwealth Avenue, what's on your mind that the average spectator is probably not thinking about?
Prashant Rao: I actually ran Boston last year, and I also run a sports cardiology clinic here at BIDMC, where I see a lot of young endurance athletes. So, when I watch a marathon, I wear three hats.
First, when I see them, I understand what's going through their head. I see someone who's been incredibly disciplined and determined, I see people enjoying something they've spent months preparing for, and I really relate to that. That's the athlete in me, right?
Second, I wear my cardiologist hat, and I can't help but think of my patients. Some of them have underlying cardiovascular issues, and even though we've carefully worked out plans so they can keep doing what they love, I still get a little apprehensive. You never stop worrying entirely.
And third, I'm a researcher. I find myself wondering—gosh that person's running quick! What molecular mechanisms are at play here? What are their VO₂ max levels like? I'm always thinking about the data behind the performance.
