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Biophysicist in Profile

David W. Piston

David W. Piston

February 2019 // 5081

Incoming Biophysical Society President David W. Piston, Edward J. Mallinckrodt, Jr. Professor and Head of Cell Biology and Physiology at Washington University School of Medicine, had his eye on a scientific career from an early age. When he was five years old, he told his parents’ bridge club that he was going to get a PhD in physics. “I always wanted to be a scien­tist, and I was fascinated by lasers as long as I can remember. I wanted to build lasers and use them to learn how matter was put together,” he shares. His father was an administrator at Fresno State, so he grew up around a lot of faculty families in Fresno, California. “It is the best place in the world to see in the rearview mirror on Friday afternoon. When I was there it was still a small town, but we were only a couple of hours from Yosemite, Sequoia, and Kings Canyon National Parks, the coast at Monterey or Santa Cruz, or the big city, San Fran­cisco,” he says. “I still love visiting, but there are way too many people there now.”

He earned his bachelor’s degree in physics from Grinnell College in Iowa, and then his PhD in physics from University of Illinois, fulfilling his childhood dream. “When I was in graduate school, the Cold War was ending, and with that, funding for ultrafast studies of electronics got very tight. I was a teaching assistant for Enrico Gratton, and his lab was using ultrafast laser spectroscopy to look at membranes and proteins,” he says. “I didn’t know very much about biology, but I really liked the measurement approaches. Fortunately, there was a great cadre of biochemists in Gregorio Weber’s and Steve Sligar’s labs that really helped me out.”

Following completion of his PhD, Piston undertook a post­doctoral position in applied physics at Cornell University, in the lab of Watt Webb. “I was lucky that my arrival coincided with the invention of two-photon excitation microscopy, which was a good fit for my skills,” he explains. “The collabo­rators I met through that approach really opened my eyes to the range of biological questions that could be addressed by combining genetic manipulations with quantitative measure­ments.”

He accepted a faculty position at Vanderbilt University in 1992. “When I started at Vanderbilt I had great measurement tools, and ideas for how to better optimize them for biology, and I was working with many biological model systems to find out what measurements were possible,” he shares. “My lab in biophysics was near a lot of diabetes-focused labs. It was Mark Magnuson who first suggested that we should start imaging pancreatic islets, and he and I remain collaborators to this day. When I was just getting started with that, though, I met Bernat Soria at the BPS Annual Meeting and he spent half a day with me going over the state of islet biophysics research.”

For about 20 years, Piston’s lab focused on the question of how the syncytium of insulin-secreting beta cells works as a unit to optimally regulate blood sugar in an animal, and the mechanisms by which those cells know that they are part of the syncytium. “This is a simple concept, but layered with complexity given the multiple molecular pathways that all play a role,” he explains. “Over the last 10 years, we have turned our attention to the glucagon-secreting alpha cells, which require the normal islet milieu for correct function. Al­pha cells clearly require multiple regulatory pathways, so they have proven difficult to understand. We have made some progress using simultaneous imaging of multiple biosensors, and one of our currently funded projects is to develop hyper­spectral light sheet microscopy for fast imaging of up to six biosensors simultaneously.”

In January 2015, he moved his lab to Washington University in St. Louis School of Medicine, where he now serves as Edward J. Mallinckrodt, Jr. Professor and Head of Cell Biology and Physiology. When asked about his favorite aspect of biophys­ics research, he said, “I like combining different approaches from genetics, molecular biology, biochemistry, physics, and mathematics to solve problems. I also like the fact that our work can potentially be translated to patient care. While we are doing very basic biology experiments, many of the mole­cules we are working with are also being targeted by pharma as potential therapies. This can create synergy between the science and the application.”

The most challenging aspect of the research endeavor, on the other hand, is its endless possibilities. “Biology is not deterministic. While we have never seen any mechanism that doesn’t follow physical rules, there is likely an infinite set of combinations that could lead to the observed result,” he explains. “So, the trick is you have to figure out what is happening, not just what could be happening. This is challenging and makes it easy to go down the wrong path at times.”

When he’s not working, he spends much of his time with his family. “I spend quite a bit of time taxiing my daughters to their activities (music lessons, gymnastics, ballet). My wife, Adrienne, and I love going to the symphony, theater, and dance,” he shares. “I enjoy choral singing, and am always looking for opportuni­ties to do challenging music.”

Piston will begin his year-long term as Presi­dent of the Biophysical Society during the 63rd Annual Meeting in Baltimore in March 2019. The Society’s meetings have been important in his career as a venue to catch up on advanc­es in the broader field outside of his area of specialization. “I have met several new col­laborators at the meeting,” he shares. “I have also met most of the students who eventually joined my lab as postdocs through the Society one way or another.”

Serving as President of the Society is one way for Piston to help lift up young biophysicists of all backgrounds. “At this point in my career, I am more interested in helping the next generation of scientists make an impact,” he says. “I am working to level the playing field for everyone who wants to work in research. The combination of intelligence, creativity, and grit needed to make an impact as a researcher can come from any background or gender. The problems we are working on are hard, and we need to leverage all of the talent available.”

His advice to those just starting out in their careers is to always make time to think deeply about their research questions. “Life has a way of getting frenetic, and there is so much pressure to get grants and publish and teach and serve on committees and… It is important to think and find what others are missing,” he says. “Sometimes, the answer is right in front of you, but you are too busy doing things to realize what you are seeing. Also, be fearless in learning and applying new techniques. It is easy to rely on the approaches you know, but those aren’t always the best way to answer your research questions.”