Meet Gladstone: Saptarsi Haldar

What brought you to Gladstone?

Gladstone is a preeminent organization in the field of cardiovascular biology. I came here for the quality of both the people and their science, which I was familiar with thanks to previous meetings with investigators and from reading their papers. It’s very rare to be able to benefit from the autonomy of an independent research institution, while at the same time being seamlessly integrated into a world-class university. Also, as soon as I visited for the first time, I felt the culture here is very special and collaborative.

What do you like about Gladstone?

The incredible quality of people in all positions here makes all the difference. And with our relatively small size, I like that if I want to talk to someone about science or administration, I don't have to send an email to an anonymous office; I can basically walk over and talk to the person directly.

Another aspect that I find remarkable, and that always impresses visitors and prospective scientists, is the open lab setting. When you stand at one end of the lab, you can look down to see row after row of contiguous bays. So many exchanges happen here, because everyone can easily communicate, and trainees can learn so much from that close proximity to their peers; it’s a huge advantage you can’t quantify.

How have been your first 2 years at Gladstone?

They’ve been great! I moved from Case Western Reserve University, and everyone at Gladstone was very efficient at helping me with the process and making it as smooth as possible. It took about a year to get the team that moved with me from Cleveland settled, get their projects back on track, and regain momentum for the lab.

The second year has largely been about recruiting new people and pushing projects toward publication. I’ve expanded the lab significantly, actually doubling the number of lab members. We also started planting the seeds for the next wave of projects, which often take 4 or 5 years to complete. They’re now beginning to grow in different, and unexpected, directions, so that’s exciting.

One of things that’s been a really great development—and one that none of us could have predicted—was the spin-out of Tenaya Therapeutics. I arrived a few months before the early conversations about this company started, so the timing was perfect and fit my skill set really well.

Were you interested in science as a child?

I’ve always been fascinated by natural phenomena. As a child, I was oriented towards science and math, and used to read books about physics and astronomy. I was always captivated by the inconceivable vastness of the universe and the possibility that there may very well be life outside of Earth. I definitely didn’t think I’d work in life sciences initially. I wasn’t exposed to biology until later in school. When I got to college, I majored in engineering, but eventually became captivated by biology and medicine because I wanted to have an impact on human health and be directly involved in patient care.

Why did you decide to pursue an academic path in science?

I went to medical school to become an orthopedic surgeon, given my interest in biomechanics. When I got there, I was drawn to cardiology instead and I was fortunate to be surrounded by really good scientists who inspired me. I actually took a year off from medical school to immerse myself in a cell signaling and biochemistry laboratory. After that, I was hooked on cell and molecular biology. To this day, I still enjoy the creative aspect of basic research and the ability to contribute to knowledge. I’m excited by the prospect of having to solve tough problems by doing very controlled experiments and understanding how the cellular machinery works normally and what goes wrong in disease. And more importantly, how we can find ways to intervene and fix it. In addition, I enjoy the privilege of mentoring and training bright young scientists and watching them succeed professionally. The contribution of new knowledge and the training of the next generation form the pillars of my mission.

Are you still a practicing physician?

Yes I am. I’m a practicing, board-certified adult cardiologist. I trained in general internal medicine, and did a fellowship in cardiology. So I take care of all cardiovascular issues in adults, such as high blood pressure, heart attacks, rhythm disturbances, cholesterol abnormalities, and heart failure.

I’ve chosen to center my clinical practice around seeing inpatients at the UCSF Moffitt-Long Hospital, in its academic cardiology division. In addition to helping very sick patients who are admitted to the hospital, I feel that inpatient clinical medicine allows me to have significant impact with clinical trainees who have aspirations of becoming physician-scientists.

As a physician, I take care of many patients with heart failure, and it drives me to find new ways to treat this devastating condition, which represents one of the biggest challenges in 21st century medicine.

Do you think being a physician changes the approach you take in your lab?

Being a physician gives you a lot of insight into the major knowledge gaps in biomedicine, and a view of the big picture. It also fuels my deep sense of obligation to find better ways to prevent and treat diseases and alleviate patient suffering. I think about how certain fundamental cellular processes or organs interact with one another, and how they all fit together, so it helps me frame some of my scientific questions. I can also leverage my broader knowledge of physiology to think about new therapeutic approaches and translation. As a scientist, I still maintain my focus on performing rigorous, hypothesis-driven science and use creative approaches to answer basic questions about how cells work and how processes go awry in disease.

What do you do when you are not working?

I enjoy spending time with my wife and our two kids. These days, much of our life is spent driving them around to different sports and activities, which is something I’m sure many of my colleagues are familiar with!

On my own time, I love playing in a pickup soccer league at Mission Bay. We have a good group of faculty, postdocs, and grad students who meet on a regular basis and are skilled players. It’s actually quite fun, and great exercise. Actually, Ken Nakamura (another Gladstone investigator) plays too and is an impressive player!

I’m also a huge soccer fan, and follow European leagues in particular. I have family living in England, so my favorite teams are from their hometowns, like the Arsenal Football Club in London or the Leicester City club, which is an underdog team. I’m looking forward to the World Cup this summer. You’ll probably find my team and I streaming games from the lab!

If you could learn to do anything, what would it be?

I always played instruments growing up, like the trombone and the piano, but I never truly learned to play guitar. I’m a very amateur guitar player, and although I can manage to play a set of basic chords, I would love to improve technically. I don’t necessarily need to be in a band, but I’d love to sit in my backyard and play.

If you could meet any scientist from any point in time, who would it be and why?

There would be two scientists, actually.  

The first goes back to my fascination with astronomy and physics; I would definitely want to meet Albert Einstein. I’ve always been captivated by his imagination and his pure creativity, and the fact that by doing thought experiments, he could reformulate the way we think about how the universe works. He questioned very basic things that we may assume we already know from everyday human experience, a characteristic of paradigm-shifting scientists. A century after he made predictions based on his theory of general relativity, we’re finding that his formulation—much like Darwin’s theory of evolution—has passed every single experimental test to date. I’d like to ask him whether he would have thought some of his theories would actually be proven experimentally, like the recent detection of gravitational waves, which just boggles the mind. I’d also like to discuss with him how he would modify his theory with some of the more recent observations in astronomy and fundamental physics.

The second scientist I’d like to meet would be the late Harold “Hal” Weintraub, who was a pioneer in cellular reprogramming and mechanisms of gene regulation. About 30 years ago, he showed that a single gene could be introduced into a skin cell to transform it into a muscle cell, which is really mind-blowing. His work cemented the concept of the master regulatory gene that could drive cell identity. This classic work has inspired several generations of scientists to discover mechanisms of cell identity, which have informed a lot of the discoveries in stem cell biology and reprogramming that have followed. I think it’s safe to say that many researchers at Gladstone would give a huge nod to Hal Weintraub. In addition to his contributions to knowledge, he left a legacy of trainees who themselves became scientific pioneers in their own right. Hal Weintraub died at a relatively young age, and I can only imagine what contributions he would have continued to make. If I could meet him today, I would love to discuss Shinya Yamanaka’s work on reprogramming to pluripotency by defined factors and Deepak Srivastava’s work on direct reprogramming to cardiomyocytes. I would also tell him that his pioneering work on master regulatory factors in muscle inspired me to change my course from being an orthopedic surgeon to the study gene regulatory biology in the cardiovascular system.