A Mechanical Engineer Turned Physiologist

When Brian Carlson graduated from the University of California (UC) Berkeley with a bachelor’s degree in mechanical engineering, pursuing a PhD was far from his mind. After graduation, Brian worked as an engineer designing machinery used to coat silicon wafers with a thin film of conductive metal (which is part of the chip manufacturing process). Brian worked alongside several engineers, one of which had his master’s degree and made it known that his advanced degree elevated him above the other engineers. That’s the moment when Brian realized that in industry, educational status matters: “knowledge is power…I’m getting a PhD”. Among other factors that encouraged Brian to think outside of industry was that the company was bought out and downsized, which gave him the opportunity of going back to school. While applying to graduate school he worked as a sales representative for a group of East Coast manufacturing companies that needed representation in northern California. Even when he was accepted to the mechanical engineering PhD program at UC Berkeley, he decided to delay starting graduate school for a year because he liked his job so much: he got to learn about all the ins and outs of the equipment and products he was selling, enjoyed the travel and solving problems that came up between customer and manufacturer.

Although a mechanical engineer by training, Brian was drawn to biomedical research for a very personal reason: his grandma was diagnosed with pancreatic cancer. Sadly, 30 years ago, this was a diagnosis with treatments limited to palliative care. “I felt helpless,” said Brian. He explained this fueled a desire to use his skills in science and medicine to help others. At the time, there were few people in the Berkely mechanical engineering department that were doing biomedical engineering research (about 2 or 3 professors max). They were mostly studying fluid flow, heat transfer and how to apply these concepts to biological systems. One of the professors was Stanley Berger, a fluid flow specialist with a PhD in mathematics from Brown University. He had a bit of funding, and accepted Brian into his lab. This lab studied the dynamics of sickle cell blood flow and how these cells moved through the capillaries when deoxygenated. They used a closed loop mathematical solution for a complex set of partial differential equations governing their motion. With this analysis they could calculate the stiffness of the red blood cells (RBCs) and oxygen concentration in the RBCs at any point in the capillary in addition to the resistance to flow in the capillary. The question they wanted to answer was what did this all mean in the context of a capillary network: what percentage of the capillary bed would shut down when oxygen concentrations dropped in the sickle RBC? This was essentially a fluid flow problem, applied to a disease and its ramifications in the vasculature.

In the early 2000’s there was only a small community working on this. Brian asked his advisor for input on who to contact for next steps and sent many emails to contacts in the field including a young research assistant professor at the University of Washington Dan Beard. Although enthusiastic about Brian’s work, Dan at the time was sharing an office, had no funding and couldn’t offer Brian a position. Eventually Brian received two offers and accepted a position with Timothy Secomb at the University of Arizona. There were many families that were part of the Secomb lab. They even shared the same childcare provider: a small, Austrian family-run daycare that often spoke in German to the kids! “It was a fun environment to be in,” recalls Brian. The time in the Secomb lab opened Brian’s eyes a lot; Tim taught him the rigor needed to responsibly apply mathematics to problems in physiology and a methodical approach to addressing and challenging hypotheses. The results may not be too flashy, but you could build upon them in future work. With mathematics many things can be discovered, but many things can also be ‘hidden’ to outsiders if the methodology is not transparent. Tim taught him mathematical methods should be used to test and exhaust all possibilities. Brian’s next postdoctoral position was with James Bassingthwaighte at the University of Washington (who happened to be Dan Beard’s PhD advisor). Jim’s style of research complemented what Brian learned from his previous mentors, he liked making bold statements without compromising scientific rigor. It was a very dynamic lab with lots of different projects, ideas, and collaborations. Many of Jim’s friends visited the lab to exchange ideas. This helped broaden Brian’s scientific scope to areas like whole body hemodynamics, cellular electrophysiology and exchange between blood and tissue in the microvasculature.

During the 2007 World Congress for Microcirculation hosted by the Medical College of Wisconsin, Brian got to reconnect with Dan Beard, who by this time had funding and was a faculty member there. Eventually Dan’s and Brian’s paths converged: Brian joined the Beard Lab in Wisconsin to Sophie’s (Brian’s 4-year-old daughter at the time) dismay , as one day she recalled: “Dad, why did you move us to the coldest place in the world?”. Despite the cold, working with Dan and his lab was great. They were able to write joint grants together, and Brian began to put pieces of his experiences together: adding electrophysiology components on fluid models of the cardiovascular system and being able to test which mechanisms were important in regulating blood flow. At the Medical College of Wisconsin, they had a hard time recruiting graduate students to join their lab. About six students a year enrolled in the department’s PhD program, and many wanted to do wet-lab science only: math was intimidating.

Brian’s journey brought him to Michigan when Bishr Omary began recruiting Dan to the Molecular & Integrative Physiology (MIP) department just as Brian began house hunting in Wisconsin. “I wouldn’t look for houses here right now” was all Dan hinted. The lab moved to the University of Michigan (U-M) and Brian recalls that his experiences have been amazing. There is a lot of support and structure in the medical school, especially within the department. This has been a very significant part of his experience at U-M. He loves now being able to interact with undergrads and grad students. There is an incredible bridge to access clinicians and clinical record databases, as well as a lot of computational and technical support. The internal opportunities for grants were outstanding at U-M as well as extramural grant writing support. Now they were not the weirdos in the Physiology department! Santiago Schnell was here doing math too.

As part of MIP Brian really enjoys his role as an associate research professor because he can do research but still gets to teach! He helps teach the PHYS 520: Computational Systems Biology in Physiology class as well as some biomedical engineering courses. “I like teaching. Sometimes it’s hard to make a lecture, just like it’s hard to write a paper, but you get the same kind of high. It’s the best feeling when you get to see a student struggling with something and after explaining the concept, ‘it clicks’ It doesn’t happen all the time,but when it does it’s a great feeling.” Brian commented.

“It’s also great to see trainees learn how to teach. This summer, in conjunction with Ben Randall (postdoctoral fellow) and Edith Jones Kiyabu (MIP grad student) in the Beard lab, I got to mentor Kiley Hassevoort (an undergraduate summer research student) as a team. It feels as if the spirit of what I learned from Stan, Tim and Jim have been passed on to Ben and Edith through me. There is a commitment to the legacy in growing the concept of responsibility in mathematical modeling in the fields of physiology and the biosciences” shared Brian.