Why study that, Ethan Lippmann?

You may know that the lines between biomedical fields are blurred, but did you know that the same is true about the boundary between engineering and biology? Hear from Dr. Ethan Lippmann about his journey into the biomedical sciences and how a basic scientist can have strong translational impacts

-by Ethan Lippmann, Ph.D.

The trajectory of my research career can be aptly described as “right place, right time” with a healthy dose of keeping an open mind. Though my lab studies mechanisms of neurovascular disease using stem cells, I had no interest in stem cells before graduate school. In fact, I had a rather myopic view of what engineers could do in the biological sciences research arena. I thought I was interested in drug discovery, and so I randomly decided that I wanted to work on protein engineering because that was the topic I associated most with my naïve interests. As such, I entered graduate school in Chemical Engineering at the University of Wisconsin and picked my adviser accordingly. Unfortunately (or so I thought), he didn’t have any projects available in the protein engineering space and wanted me to work on blood-brain barrier (BBB) models instead. As he said, the lab really needed a good BBB model to test whether their new antibodies could delivery payloads into the brain, and I was tasked with improving the current model in the lab that utilized primary brain endothelial cells from rats.

I’ll be honest – I was pretty bummed out at this point. I wanted to work on designing new therapeutic compounds, and instead I was euthanizing rats every week to create what I thought was a middling cell culture model of the BBB. But, I kept an open mind, worked hard, and characterized that model ad nauseam (and I was indeed nauseous from all the bloody animal work). As for the “right place, right time” aspect, I happened to share an office with a fellow graduate student who worked in a lab that was culturing human induced pluripotent stem cells (iPSCs). Wisconsin is considered a stem cell hub, as the first human embryonic stem cells were derived on the campus, and plenty of researchers on campus were trying to make endothelial cells. After thinking a bit about the technology available to me, I came to a conclusion: why couldn’t we make brain endothelial cells from iPSCs with functional BBB properties? My adviser agreed that it was worthy of a try. With my office mate and fueled by many cups of coffee, I powered through the trial and error process of making a brand-new cell type from iPSCs. I will admit, we experienced many crushing defeats that made me initially regret proposing such a bold idea that was not backed up by any existing literature. But, we ultimately succeeded through hypothesis-driven explorations and simple trial-and-error experiments coupled with the power of observation. After our first paper was accepted, I knew that I wanted to stay in academia, to carry out research that I had designed and created, and to also mentor students that would otherwise fall prey to my own previous small-minded views on research interests.

As it turns out, life often comes full circle, and keeping an open mind in graduate school has led me into a fulfilling academic career. The BBB community was relatively small when I entered graduate school, but now it seems like every neurological disease I read about has some link to abnormal BBB function or vascular pathology. Every day in the lab, my students get to use iPSCs to explore mechanisms of BBB development and disruption during disease, and I couldn’t be more excited when they bring me new data showing a potential pathway that might disrupted in crippling diseases like Alzheimer’s. Thankfully, my previously myopic view on what engineers can do to enhance biological sciences has also been shattered. At Vanderbilt, I get to team up with other like-minded engineers to build the next generation of three dimensional neurovascular constructs and use techniques like CRISPR to identify better ways of getting drugs into the brain. One day, we may be able to use the knowledge gained from our models and screens to actually help bring a therapeutic treatment into clinical practice. I would say that’s a pretty satisfying career arc for a failed protein engineer like myself.

The trajectory of my research career can be aptly described as “right place, right time” with a healthy dose of keeping an open mind. Though my lab studies mechanisms of neurovascular disease using stem cells, I had no interest in stem cells before graduate school. In fact, I had a rather myopic view of what engineers could do in the biological sciences research arena. I thought I was interested in drug discovery, and so I randomly decided that I wanted to work on protein engineering because that was the topic I associated most with my naïve interests. As such, I entered graduate school in Chemical Engineering at the University of Wisconsin and picked my adviser accordingly. Unfortunately (or so I thought), he didn’t have any projects available in the protein engineering space and wanted me to work on blood-brain barrier (BBB) models instead. As he said, the lab really needed a good BBB model to test whether their new antibodies could delivery payloads into the brain, and I was tasked with improving the current model in the lab that utilized primary brain endothelial cells from rats.

I’ll be honest – I was pretty bummed out at this point. I wanted to work on designing new therapeutic compounds, and instead I was euthanizing rats every week to create what I thought was a middling cell culture model of the BBB. But, I kept an open mind, worked hard, and characterized that model ad nauseam (and I was indeed nauseous from all the bloody animal work). As for the “right place, right time” aspect, I happened to share an office with a fellow graduate student who worked in a lab that was culturing human induced pluripotent stem cells (iPSCs). Wisconsin is considered a stem cell hub, as the first human embryonic stem cells were derived on the campus, and plenty of researchers on campus were trying to make endothelial cells. After thinking a bit about the technology available to me, I came to a conclusion: why couldn’t we make brain endothelial cells from iPSCs with functional BBB properties? My adviser agreed that it was worthy of a try. With my office mate and fueled by many cups of coffee, I powered through the trial and error process of making a brand-new cell type from iPSCs. I will admit, we experienced many crushing defeats that made me initially regret proposing such a bold idea that was not backed up by any existing literature. But, we ultimately succeeded through hypothesis-driven explorations and simple trial-and-error experiments coupled with the power of observation. After our first paper was accepted, I knew that I wanted to stay in academia, to carry out research that I had designed and created, and to also mentor students that would otherwise fall prey to my own previous small-minded views on research interests.

As it turns out, life often comes full circle, and keeping an open mind in graduate school has led me into a fulfilling academic career. The BBB community was relatively small when I entered graduate school, but now it seems like every neurological disease I read about has some link to abnormal BBB function or vascular pathology. Every day in the lab, my students get to use iPSCs to explore mechanisms of BBB development and disruption during disease, and I couldn’t be more excited when they bring me new data showing a potential pathway that might disrupted in crippling diseases like Alzheimer’s. Thankfully, my previously myopic view on what engineers can do to enhance biological sciences has also been shattered. At Vanderbilt, I get to team up with other like-minded engineers to build the next generation of three dimensional neurovascular constructs and use techniques like CRISPR to identify better ways of getting drugs into the brain. One day, we may be able to use the knowledge gained from our models and screens to actually help bring a therapeutic treatment into clinical practice. I would say that’s a pretty satisfying career arc for a failed protein engineer like myself.

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