Meet Svetlana Lutsenko

An  associate editor of the Journal of Biological Chemistry

Lutsenko

Svetlana Lutsenko at The Johns Hopkins University joined the ranks of the associate editors at the Journal of Biological Chemistry last year. Her laboratory focuses on copper homeostasis. The interview has been edited for length and clarity.

Would you briefly explain what your research group is studying?

We work on human copper metabolism. We are very interested in it, because copper is an essential metal for human growth and development, and disruption of copper homeostasis causes a wide spectrum of pathologies. As an essential enzyme cofactor, copper is important for respiration, for formation of vascular tissue and for brain development. Enzymes that require copper as a cofactor produce catecholamines, so whether we are happy, sad or depressed very much depends on whether we have sufficient copper.

There are two well-described human diseases that have been known for almost a hundred years that are caused by copper imbalance. Menkes disease is an X-linked chromosomal disorder affecting boys. They invariably die because they are deficient in copper absorption in the gut and copper delivery in the brain. The other disease is Wilson’s disease, which is a disease of copper overload.

In the past two decades, copper research has progressed significantly. Starting from having only cDNAs of genes and no experimental information about copper transport across various membranes, we and others have gained a lot of insights into how transporters work and how they are regulated in a cell.

Using genetically engineered mice to study Wilson’s disease helped us to uncover new metabolic links between copper homeostasis and lipid metabolism. We have characterized a mouse model for Wilson’s disease that is now used by a lot of people. My mice, I tell people, are better traveled than I am. Right now, we are trying to generate a comprehensive picture of how transporters work in human cells and how they are regulated – and also what happens in disease.

The more I learn, the more interesting it becomes, because we now know that copper intersects with many metabolic pathways. We have discovered there is a very tight connection with lipid metabolism, and right now we are really very excited about learning more about the role of copper in adipocyte maturation. Also, we are very interested in neuronal degeneration and how copper contributes to CNS development and function.

Tell us about your academic background and research training.

I received my undergraduate degree at Moscow State University; I was born in Moscow. I was really torn initially between chemistry and biology, because I really like chemistry; but I also like furry and fuzzy things, and biology seemed appealing.

I was always interested in membrane transporters. I’m just really fascinated. What’s going on in the membrane? How do cells talk to each other? How do they get stuff in? Out? When I was an undergraduate student, I decided to do my undergraduate research working on the Na+/K+-ATPase and the Ca2+ ATPase.

I did my Ph.D. in membrane biology working on the Na+/K+-ATPase, trying again to understand how this transporter works. The institute where I did my Ph.D. is the Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry. Their strength is in membrane biology, so it was very good for membrane biology and biochemistry of membranes.

After that, I realized it would be really nice to have advanced postdoctoral training, and fortunately or unfortunately the Soviet Union was starting to fall apart … so I had an opportunity to go abroad and do a postdoc. I did my postdoctoral studies at the University of Pennsylvania in the physiology department. I continued to be interested in membrane transporters and expanded my studies to look at the functional role of the beta subunit of the Na+/K+-ATPase and conformational changes associated with the transport cycle.

While I was at Penn, I became interested in copper. Then I moved to Oregon Health & Sciences University. I was hired there as an assistant professor. I went through the ranks at OHSU and established my independent lab, and then I came to Hopkins in 2009 as a full professor.

Hopkins is really great because people are so interested in science here and we can work with clinicians. We have very good collaborators in the department of medicine, so we can actually start translating our findings. We are still in the early stages, but we have started treating animals with drugs and we have had certain small successes at improving liver function in the Wilson’s disease animal model.

Did anything occur, in a milestone sort of way, that made you choose science as a career?

I have always wanted to investigate something. As an 8-year-old girl — I think this was unusual — I wanted to be a detective.

My parents are both scientists. My mom spent most of her time teaching, and my father was a scientist. I just wanted to learn how everything works.

What does it mean to you, on a personal level, to be an associate editor for JBC? What was your reaction when you were asked to be an associate editor?

Oh, I was delighted! I was really delighted, because I remember JBC being my favorite journal as a graduate student.

I was in Russia. At that time — it is funny how things change — we couldn’t check magazines out of the library without permission. Everything was so controlled, all the information. We could make a Xerox copy only after filing a request and getting signed permission for every page. So I was carrying this big green JBC magazine back and forth, and because I wanted to read quite a few of them and they were very thick at the time, it was a lot of exercise just to carry the JBC to the Xerox copier and back.

Scientific journals were the only way you could get knowledge of what was going on (in the West). The first time I came to the United States in ’89 and saw all these people who published these papers, it was wonderful. Then becoming an associate editor of the journal that I used to go and get permission to copy from the library — it was really very nice.

What do you think is the most exciting thing about science these days?

I remember I would go to a cell biology meeting and many studies were fascinating but rather descriptive, and I would go to biophysical meetings and though that technology is great, the questions were far from real biology.

Now, we have this synergy where there are great technologies that are finally coming to the stage where we can apply technology and really address, mechanistically, fascinating questions about development, about cell programming, about regulation. The most fascinating aspect of science right now is that it is easier to study fascinating biological questions mechanistically. Like for real, with tools, and technology, and resolution, and numbers.

For scientists in training, do you have any words of wisdom or a favorite motto?

What I tell people in my lab is this: As long as you’re interested in what you do, things will fall the right way. I believe it is very important to do not necessarily what is fashionable today but what you feel excited about, because fashions change. Of course there are ups and downs, and there always are, and things are sometimes harder, sometimes easier. Some fields are sexier than others, and they are somewhat easier, maybe, in terms of funding, but there’s also more competition. I think the way to have a good time is actually to like what you do.

Mollie Rappe Mollie Rappe was an intern at ASBMB Today and is a Ph.D. candidate in biophysics at Johns Hopkins University.