HUBweek Change Maker: Arun Sharma, Ph.D.

Research Fellow, Harvard Medical School, Department of Genetics

Arun Sharma is a postdoctoral research fellow in the Harvard Medical School Department of Genetics, where he works with induced pluripotent stem cells (iPSCs) and CRISPR to investigate the mechanisms of congenital heart disease. Previously, he studied the effects of microgravity on human physiology, sending heart cells to the International Space Station. In 2017, Sharma was named one of Forbes’ 30 Under 30 for Science, and a STAT Wunderkind.

How did you first become interested in working with heart cells, and working at the intersection of cardiology and space travel? What continues to inspire you about this work?

I first became interested in heart cells when I learned about the human heart’s limited ability to regenerate itself after an event such as a heart attack. The cells of the heart don’t divide, so this is part of the reason why damage to the heart is often irreversible. This is contrast to the skin, for example, which is largely able to regenerate itself after injury. I wanted to figure out ways to better understand the cells of the heart, in hopes of one day being able to better repair the heart. This interest led me to learn about induced pluripotent stem cells (iPSCs), which are stem cells that can be made from a small sample of skin or blood through a process called reprogramming. From these iPSCs, we can for the first time mass-produce patient-specific human heart cells, and use them as a cellular model to study a variety of environmental stimuli such as microgravity. Since it is not well understood what happens to the individual cells of the heart during long term exposure to microgravity, we decided to use these iPSC-derived heart cells as a model system. Figuring out what happens to the cells of the body during long term exposure to microgravity is useful, since humanity will be spending more and more time in space during missions to Mars and beyond.

As a graduate student, you were involved with a study that sent heart cells into space on a SpaceX rocket. What was that experience like for you? What were the results of the study, and what are some of its future applications?

Getting the opportunity to send a sample of stem cell-derived heart cells to the International Space Station was an exceptionally unique opportunity that I was very fortunate to be a part of. From a professional standpoint, it is incredible to be able to utilize the ultimate microgravity laboratory in the International Space Station to study the effects of spaceflight on the human body, and collaborate with astronauts who were able to maintain our experiment on orbit. And from a personal standpoint, being at the launchpad to observe the SpaceX rocket carry my experiment to the International Space Station…wow. It’s hard to describe the experience. Knowing that something that you worked on for years was being launched to space aboard this one rocket…certainly it was a nervewracking moment, but we were fortunate in that the launch and delivery to station went off without a hitch. It was such a unique experience, and thanks to our collaborators at SpaceX, NASA, the Center for the Advancement in Space, and BioServe Space Technologies, we were able to conduct a successful one month study. From the results of our study, we have learned that the individual cells of the human heart change quite rapidly after being exposed to microgravity. The heart as a whole organ is known to change its shape and size, as well as lose some of its muscle mass on orbit, since it doesn’t have to work as hard in microgravity. This is similar to what happens to the other muscles of the body in microgravity as well. The heart cells, similarly, change their beating patterns and actually do not exert as much force on the single cell level, which in some ways parallels what happens to the heart as a whole. By better understanding how the heart cells behave in low gravity, we may be able to uncover new mechanisms that will enable us to strengthen the heart and muscles during long-term space flight.

What are you working on now? Pluripotent stem cells, CRISPR, and personalized medicine — we’d love to hear more. What impact do you hope to have?

Currently, my work at the Harvard Medical School Department of Genetics focuses on using iPSC-derived heart cells to study the mechanisms of congenital heart disease. Thousands of children are born with heart malformations on a yearly basis, and we believe that the iPSC-derived heart cell system can serve as a model to better understand the mechanisms of just how these malformations develop, and potentially, uncover new mechanisms that would allow us to better treat congenital heart disease. In a nutshell, we are identifying unique genetic variants that cause congenital heart disease, introducing those genetic variants into iPSC-derived heart cells using CRISPR genome editing, and then further studying how those genetic mutations cause the heart cells to behave differently in a “disease-in-a-dish” approach.

What are you most excited about for the future of cardiac research? Do you see any breakthroughs on the horizon?

As a stem cell biologist, I believe that one of the ultimate goals in regenerative medicine is to be able to mass produce organs and tissues in a way that would alleviate the organ shortage crisis which is preventing thousands of individuals from receiving transplantable organs. We are not quite at the point of being able to make an entire heart “in-a-dish”, but we are taking the first steps towards that ultimate goal. It certainly will be an incremental process, beginning with better understanding the mechanisms of how heart repair and regeneration occurs on the single cell level, using model systems such as these stem cell-derived heart cells. From the lessons we learn at the cellular level, we can then take the next step towards building realistic cardiac tissues and ultimately, functional human hearts. There is still so much to learn not only about the heart but about the mechanisms that contribute to tissue generation and regeneration as a whole. These unsolved questions, combined with the amazing new technologies such as CRISPR, iPSCs, and next generation genome sequencing, make it a very, very exciting time to be involved in cardiovascular biomedical research.

What are some of the biggest challenges you’ve faced in your career as a researcher? What has helped you overcome them?

As a young scientist, one of the first things that you must learn is how to fail, how to fail effectively, and how to learn from your failures. Science is mostly failure…failed experiments and hypotheses are commonplace! Learning how to fail effectively is hard, and it really can be discouraging in the beginning especially since you can devote a significant amount of time and effort to a project, only to have it not pan out. But, the beauty of modern science is that it is highly collaborative and no one fails alone. I have been very fortunate to have a tremendous group of mentors who have helped pick me up after my failures, taught me to fail effectively, and given me encouragement to keep looking forward.

Do you have any advice for other young scientists?

As cliche as it might sound, I am a firm believer in following your passions, since if you truly love what you do, you will end up naturally giving 110% to it. Find a topic or area of interest that excites you, not just because you can see the impact that it would have down the road, but because you enjoy the day-to-day work in making that impact a reality. For me, it’s something as simple as seeing human heart cells beat in a dish. Beating heart cells that were made from stem cells from a small sample of skin…I get to work with them every day. How cool is that? I truly believe that we are living in a golden age for biomedical research, and I feel so fortunate to be a part of it.

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