Completing a jigsaw puzzle? NKI alumna Henne Holstege: “I’d rather work on a scientific text”

01-08-2023

Every year, dozens of researchers at the Netherlands Cancer Institute defend their thesis and receive their PhDs. How do they find their way to a science career afterwards? A conversation with Henne Holstege about dissecting old brains and following your heart.

20 years ago she was at the Netherlands Cancer Institute, studying the differences between tumors in mice and those in humans, but now she is investigating different comparisons. How is it possible that some elderly people don’t develop dementia, while many people of the same age cannot escape the condition? Henne Holstege is fascinated by healthy elderly people and enjoys the company of people over the age of 100. Ten years ago she founded the 100-plus Study, in which she compares centenarians with dementia to those without this condition. She is a university lecturer at the Amsterdam UMC and leads her own research group.

Where did your fascination with the elderly come from?

During my PhD research, Hendrikje van Andel-Schipper passed away at the age of 115. When she was alive, my father, professor in neuroanatomy, had her on his radar. She had a sharp mind despite her very old age. When she passed, her brain was comparable to one belonging to a sixty year old. Her mother had also had a sharp mind when she passed away at the age of 100. Was it something in the family? It was fascinating to me, so I knew what I had to do: figure out how that was possible. Why do some people develop dementia while others grow very old in perfect health? Is it hereditary?

But your PhD was in cancer research… what happened?

Once I completed my PhD, people warned me against pursuing a career in science. I would have to keep myself afloat financially and fund my own research group and it would all be very stressful. I started working in the clinic, training as a clinical molecular geneticist. But I found out quickly that my future was in science. I didn’t complete my training and started my own lab.

Setting up your own lab, how did you manage to do that?

I followed my heart. I didn’t really have a plan, I just did what I felt was needed. The people around me have been vital to me. People who believe in me, who supported me through thick and thin, whom I can trust. I cherish those people. I now have a great group of about 25 enthusiastic and driven people, and we collaborate with researchers across the world.

How is your work-life balance?

I have three beautiful daughters and a husband. They think that I spend too much time at work. But while others may enjoy jigsaw puzzles, I like to work on a text for a scientific paper. That’s more exciting to me.

How do you look back on your PhD research at the Netherlands Cancer Institute?

One thing that stuck with me more than anything is the close connection between PhD students at the NKI. We have all experienced a time in our lives that matures you as a person and as a researcher. I got the hang of various different research methods, in the lab and with mice. I investigated to what extent DNA changes in mice differs from those in people. Quite a lot, I discovered. During the years at the NKI I saw the importance of bio-informatics for molecular research. We used to work on the sequencing of expression levels of 1 gene, transcript, or protein for years, but now we measure everything genome-wide, proteome-wide, transcriptome-wide… that’s hard to grasp without large-scale statistical analyses. You can’t even imagine research without bio-informatics.

Now you study the DNA of centenarians. Still genetic research, but in a different context, How different is that?

It is an exciting time for neuroscience, with plenty of discoveries. We are 30 years behind on oncology, but the techniques that are being developed for cancer research can now also be applied to our field. We can take very precise, large-scale measurements from small tissue or blood samples. I am very grateful to the centenarians who participate in our study. They allow us to investigate and understand how the brain can stay healthy at a very old age.

You’re speaking very lovingly about the centenarians participating in your study. How well do you know them? Did you gain several new grandmas?

Initially I visited all centenarians myself, and anyone you’ve met gets a place in your heart. The same goes for the three staff members in our team who set out every day to meet with centenarians and their families. The last participant I had included myself recently passed away at the age of 108. Some people seem to have eternal life, and it sucks when they do eventually die. During the yearly centenarian day, when we invite all centenarians to come have a big, elaborate lunch, we celebrate the collaborations with the people aged 100 and up. That truly is the best day of the year.

Completing a jigsaw puzzle? NKI alumna Henne Holstege: “I’d rather work on a scientific text”

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