Faculty Spotlight: Precision Pediatrician, Sushma Reddy

by Adrienne Mueller, PhD
April 17, 2023

Sushma Reddy, MD, is an Associate Professor of Pediatrics in the Division of Cardiology at Stanford School of Medicine. In this faculty spotlight interview, we discuss her motivation to pursue translation medicine in pediatric cardiology, the potential of precision medicine to help children with heart disorders, and the challenges facing her field.

Were there any key experiences that led you to where you are now in your career?

During residency, we had a research talk by a pediatric cardiologist named Dr. Seema Mital. At that time, she was one of very few clinical pediatric cardiologists who did basic science research, and it was extremely motivating to see someone could be a heart failure transplant doctor and do basic science research. Her goal was to identify medications that would treat heart failure in children in particular. I was inspired by how she was able to bring the questions at the bedside back to the bench, so that whatever was done in the lab was directly translatable to a problem a group of patients was facing.

What drew you specifically to the field of pediatric cardiology?

Definitely the complexity of congenital heart disease. It's impossible to say that any two children born with congenital heart disease are the same. The disease is extremely complex, but at the same time the tremendous advances we've made in the last three decades have led to incredible advances and improvements in survival. We are actually seeing children living into their teens, 20s, 30s, and some of them even into their sixties. With this improvement in survival comes important residual disease in those with more complex disease which can be a unique challenge. While I do think we can begin to identify common themes in these patients, there will always still be that component of individualizing therapy, since the inciting insult for heart failure in children is specific to each child.

How is your research tackling the problem of finding therapies for these unique cases?

We’ve shown over and over again that adult heart failure therapies don't uniformly help children with congenital heart disease. In fact, some therapies that are standard of care, such as the beta blockers for adult heart failure, are actually detrimental in some pediatric patients with congenital heart disease. So, our first goal is to better understand pediatric heart failure before we identify therapies. However, to do so is not easy. Animal models of the more complex congenital heart disease often do not survive. Getting tissue from patients to better understand what's causing their heart failure poses risks to the patients. Consequently, we use the plasma or blood to serve as a liquid biopsy of what's happening within the heart. Circulating substances reflect what is happening in the heart, as well as the systemic response to what’s happening in the heart. This method captures the changes occurring within the heart over time, which can be used to readily understand disease progression and perhaps to follow response to therapies.

What sort of therapies for pediatric congenital heart disease are you using your liquid biopsies to test?

Metabolic properties and in particular, mitochondrial dysfunction, is a big area of interest. In developing non-invasive markers to understand myocardial events, we're seeing over and over again that mitochondrial dysfunction precedes heart failure. So, how can we better protect the mitochondria so we can preserve the longevity of the heart? We are working with several companies who have developed mitochondrial targeted therapies to treat non-cardiac disorders to see if we can repurpose them for children with pediatric heart disease. The goal is to better understand mitochondrial dysfunction and pediatric heart failure, then test these therapies in the dish before we take them back to the patient.

If you have a promising therapy in a dish, how long will it take be able to be able to deliver it to a child patient?

Some of the small molecules we are currently testing have been approved in pediatrics in terms of their safety and are in phase II and III clinical trials for other conditions. Therefore, we are looking at the next three years before we can launch a clinical trial in children with certain forms of heart failure.

What do you think are the biggest challenges facing research in pediatric cardiology?

I think one of our biggest problems is our difficulty in doing clinical trials. Because our patient population is smaller and is more heterogeneous. We would need all the centers in the US to get together to do a clinical trial. On a totally different level, we also have to ask ourselves: is doing clinical trials in the traditional way actually the way to move forward? Or do we need to learn from teams that test drugs in a dish, and get more data before we perform clinical trials. Moving forward, I think we need to identify pediatric-specific heart failure therapies and to come together as a society to think of how we can perform effective clinical trials, or, implement alternatives to clinical trials. In the last decade, there are more scientists with varied skills in bioengineering, stem cell biology, material science, and other disciplines, who are pursuing congenital heart disease research, which can only bring great things to this field.

You care a lot about education and mentorship. What motivates you to dedicate your time to helping foster the next generation of cardiology researchers?

I think it goes back to being in Dan Bernstein's lab when I arrived at Stanford. He was such a good listener, an amazing advocate, and a wonderful mentor and sponsor. He was always available to me, and even today he is still there to support me. I found that level of selfless work, time, and effort so inspiring. Because of this, I’m trying to give back in my own way, a little bit of what I've received from Dr Bernstein and other mentors.

The pediatric cardiology research community has to learn how to better support our junior scientists so that we can retain them and maintain a channel of discovery in our field. This is not easy in a clinically heavy field. To prevent early attrition,  we need to give them as much support as possible when they're starting out. For example, our Chair of Pediatrics has created a wonderful mentoring committee for instructors and assistant professors. She has also created bridge funding mechanisms for junior scientists. We need a way to continue and expand on these wonderful mechanisms into associate professorship and beyond. I also think we should help make team science feasible for the junior scientist by partnering them with senior scientists to collaborate and pursue funding opportunities together, so that we can constantly learn and grow from the team around us.