Form Follows Function: Jesper Pallesen on Biology & the Structure of Things

What is your research?

I specialize in immunotherapy development against infectious diseases and cancer. First and foremost, my team and I are structural biologists, so we use cryo-electron microscopy to analyze the structures of proteins at a very high resolution. We go to a resolution that’s high enough that we can almost see the atomic placement in protein structures and how everything fits together, kind of like Legos.

With this level of analysis, we know exactly where the parts of the protein that interact with other molecules sit, which can tell us what both the protein binds to and how that binding works.

What’s the “cryo” in “cryo-electron microscopy”?

Basically, cryo-electron microscopy is electron microscopy performed at very low temperatures, which ensures that the samples don’t move while we shoot electrons at them (which is how we get the image). Once the sample is frozen, then we use the microscope. If the proteins were moving around, we would get blurry images.

Tell us about your education route.

My first existential crisis happened when I no longer wanted to study physics in undergrad. Physics was something I had wanted my whole life until I didn’t. I took some time away from studying and did some soul-searching. And then I started studying biology and realized it was really my home. I’ve never been more thrilled than with biology studies.

Then what happened?

I applied to the biology program. That was life changing.

I did my undergraduate and graduate studies at the University of Aarhus in Denmark. My undergraduate studies in biology were the sandbox of my life. It was amazing. I couldn’t stop reading the textbooks, which is insane, right? You had to drag me out of my study room.

I started my Ph.D. at the University of Aarhus and realized I had bigger ambitions, but I finished with a nanotechnology Ph.D.

I interviewed with Dr. Joachim Frank’s group at Columbia University in New York and was offered a postdoctoral position. Dr. Frank is a Nobel Laureate for development of the cryo-electron microscopy technique. That’s my expertise and my training in cryo-electron microscopy started at Columbia University.

Columbia University was an amazing place: academically rigorous, ambitious people, good budgets, just really an amazing time. I did five years as a postdoctoral fellow and then in 2013, I left Columbia University and my apartment in New York.

I took some time to explore my options. I studied IP law as a paralegal and learned a lot about patent applications. But I found that I missed the math, and I moved to San Diego to get an MBA from Rady School of Management, University of California San Diego, while I did a second postdoc at Scripps Research. Afterwards, the timing was better to start my own research team, so I did.

What is one takeaway from all the different educations you embarked on?

The number one question I get asked is, ‘Why did you get an MBA when you went the academic route?’ And the answer is I wasn’t planning on taking the academic route. But now that I am a professor, it’s the best thing that I have ever done. My MBA is such a help in managing my group, my finances and time management. I highly recommend people make this investment in their own careers.

Who is your mentor and why? Who influenced you the most?

Joachim Frank from Columbia influenced my career tremendously, and Erica Ollmann Saphire at La Jolla Institute of Technology continues to be my mentor; she was someone who saw the talent in me. I owe Erica so much, and I consider her a close friend of mine.

When you work with Wistar’s Dr. David Weiner, at what point in the research do you get involved?

All the time. I have a standing meeting once a week with David. We coordinate pretty much everything between our two groups. We’re organized in a consortium style, so we’re fully integrated. My team does all the structural biology, all the molecular design.

We’re involved at the beginning in the design process. So, before we even start to design a new technology, we’re evaluating whether it’s a good idea or not. And then later, when we get tissue samples back, we characterize whatever was found.

What motivates you to do what you do?

My love of biology and having a real impact in this world. I want to save lives and make sure that we advance new drugs & treatments to the clinic that go out to the market and then to hospitals. We’ve done that with a handful of products and technologies, and the impact of what I’ve been doing over the last 10 years has saved millions and millions of lives.

What are the goals you most want to accomplish?

As for scientific goals, my collaborators and I have already developed multiple vaccines and made a global impact through our research. We developed antibody cocktails against viruses like SARS CoV-2 and Ebola. I consider those fulfilled goals.

Going forward, I want to work on a treatment for HIV, and I also want to take the lessons we’ve learned with antibody development and apply them to cancer. Our cancer advances are already bearing fruit.

What keeps you up at night?

What keeps me up at night is cancer. There are so few quality treatments on the shelves and so much morbidity and pain in this world caused by cancer. So that’s what keeps me up at night and that’s what makes me continue to come to work.

What might someone be surprised to know about you?

I grew up a tennis player. But my knees aren’t what they used to be, so now I play horseback polo. It’s more dangerous in certain ways than tennis, but it’s very exciting.