Steering Cancer Cells Back to Normal: 8 Questions with Kristian Helin

Kristian Helin in his laboratory

"As a cell biologist, I’m always trying to understand the basic mechanisms of how cells work," says Kristian Helin.

Kristian Helin is the new Chair of the Cell Biology Program at the Sloan Kettering Institute and Director of the Center for Epigenetics Research at MSK. He came to MSK in 2018 from Copenhagen, where he was Director of the Biotech Research and Innovation Centre at the University of Copenhagen.

Your lab works on epigenetics. Can you explain the topic?

The term “epigenetics” can mean different things to different people. I remember being at one meeting at Cold Spring Harbor Laboratory in 2008 where there were lengthy discussions and lots of disagreements about a definition.

Originally, “epigenetics” referred to changes in cell behavior or identity that are inherited from a parent cell to daughter cells — and perhaps even from one generation to the next — that are not the result of changes in the DNA sequence itself. But I would say most people working on epigenetics today use a looser definition. “Epigenetics” more broadly describes how the packaging of DNA into chromatin can influence which genes are expressed in a cell.

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How exactly does that work?

DNA doesn’t exist as a naked molecule in cells. It’s wrapped around proteins called histones and modified with small chemicals. Collectively, this assembly is called chromatin. Proteins and other molecules that bind to histones can affect how tightly the DNA is wound and which regions of the genome are open or closed.

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Can you talk more about the relationship between epigenetics and cancer?

The genes encoding the proteins that bind to chromatin are often mutated in cancer. These mutations lead to altered patterns of gene expression that cause cells to divide out of control. Drugs that target these mutant proteins are now an important part of cancer therapy.

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What is your lab working on now?

We’ve been trying to understand how proteins that bind to chromatin control gene expression. Our model is that these proteins keep gene expression patterns stable and in this way help preserve a cell’s identity. That’s very relevant to cancer, since cancer cells can be thought of as being in the midst of a kind of identity crisis. Our ultimate goal is to figure out how to tweak these proteins to steer wayward cancer cells back to a normal path, bring them back into the fold, as it were.

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What attracted you to MSK?

It was a very natural progression for me to come to MSK. As a cell biologist, I’m always trying to understand the basic mechanisms of how cells work. Over the years, I’ve become more interested in how my research might be therapeutically useful.

You might think that translating basic science into therapies would be easy. It’s not. There is a huge gap between basic scientists and doctors. MSK is one of the few institutions in the world where you have top-level basic science and top-level clinical science at the same place.

As a cell biologist, I'm always trying to understand the basic mechanisms of how cells work. Over the years, I've become more interested in how my research might be therapeutically useful.
Kristian Helin cell biologist
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Had you done much work in the United States before you moved here from Denmark?

I came to conferences here a lot as a graduate student, I did some research stays at the National Institutes of Health, and I did my postdoc at Harvard. I love the way science is done in the United States.

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What is different about it?

I think science in this country is just very high on the agenda. When I lived in Boston, I was astounded by how much science was around. The same is true in New York. You feel like people are extremely committed and want to make a difference. There is a very high level of optimism around doing things here.

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Did you come from a scientific family?

I never thought I was going to be a scientist. I grew up in a small town in the countryside of Denmark, the youngest of four children. My father was a veterinarian. My mother was a pharmacist. I actually thought that I would study political science until the day I sent my application to university.

I ended up studying chemical engineering at first. But then I got hooked on molecular biology. That area was fascinating to me and, ultimately, the direction I took in graduate school.

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