Faculty Q&A: Anna Huttenlocher

Dr. Anna Huttenlocher is a professor of pediatrics and medical microbiology and immunology at the University of Wisconsin School of Medicine and Public Health in Madison. In the following interview, the new director of the MD/PhD program talks about taking a risk on zebrafish to advance her research program and helping students transition to their own scientific careers.

You soon will become the new director of the MD/PhD program. What does that mean for you?

I've been very involved in the program as associate director for the past 12 years. I'm very excited about leading the program and continuing the tradition of excellence Deane Mosher has established as director.

I run my own large research program and as the director of pediatric rheumatology at American Family Children's Hospital I have a large clinical practice, so it was a difficult decision. But I'm very committed to training physician-scientists.

How will this affect your clinical practice?

I'll cut back on my clinical work significantly, passing patients to a recently hired member of the pediatric rheumatology team and reducing my inpatient service from four months to six weeks a year. I love clinical medicine so I'm a little sad about this, but I feel sometimes it's important to make these kinds of transitions.

What was your own journey into research like?

I first became very interested in research when I was at Oberlin College. My plan was to go to graduate school, but I decided on medical school after my mother was diagnosed with lung cancer. I went to Harvard Medical School but they didn't have a combined MD/PhD program then.

After my internship and residency, I became immersed in research during a fellowship in pediatric rheumatology-immunology at the University of California, San Francisco, and I completed four years of basic research training as a pediatric scientist development fellow, which helps pediatricians transition into research. My post-doc research focused on understanding the basic mechanisms that regulate cell migration.

How has your clinical practice informed your research?

In my practice, I see children with autoimmune diseases and immune dysfunction, mostly childhood arthritis and lupus. I wanted to study my patients' immune cells in the lab. Our first in vitro studies showed that in some patients with inherited chronic inflammatory disorders known as auto-inflammatory diseases, their neutrophils didn't migrate normally to inflammatory cues - they moved very slowly. I wanted to understand better how these immune cells move in a live organism and why patients develop chronic inflammation.

Enter zebrafish?

Yes, zebrafish were a better choice than model research organisms like fruit flies and worms because zebrafish are a vertebrate genetic model with a vasculature and an immune system quite similar to that of mammals. Best of all, of course, the fish are transparent and you can watch live cells move in them under a microscope. So I took a risk in 2001, just after starting my own research program, and began using the zebrafish for observing the movement of their immune cells in response to tissue damage.

What did you find initially?

What became clear, to our surprise, was that neutrophils and leukocytes would go to the wound site, spend a little time there and then they would leave. That went against dogma, which held that neutrophils would go to a wound site, do their job and then undergo apoptosis - die. Macrophages then would come and clear them out. Intuitively, it didn't make sense to me that with a minor wound, say a scratch, you would go through this whole process, including dying. It seemed wasteful.

How did you advance that work?

In order to publish our finding that neutrophils were going to the wound site and then leaving as a form of resolving the response, we needed to develop a fluorescent reporter line, and that took a couple years. Eventually we expressed green fluorescent protein under the neutrophil-specific promoter MPO and could very clearly see this reverse migration - neutrophils weren't dying at the site, they were leaving it. Ours was the first study to show that reverse neutrophil migration occurs in live animals.

How did the scientific community take this new information?

There was a lot of resistance at first. It was incredibly hard to publish this paper since it went against dogma. People thought our findings might be an artifact of our zebrafish model. But now reverse migration is pretty widely accepted-and has recently been demonstrated in mouse models as well. Maybe textbooks will be changed.

What clinical implications might come from this?

Our ongoing findings and new findings others are making these days may change the way we think about inflammatory responses. Do patients with autoimmune diseases and immune dysfunction have impaired migration that leads neutrophils to be trapped within tissues? Could we find a way to release them? We think zebrafish and perhaps mouse models can answer important questions such as these.

Is it fair to say you've had a flurry of papers in high-profile journals lately?

Yes.

How do graduate students figure in the picture?

I currently have five graduate students and five post-docs in my lab. They take leadership roles on their projects and are critical for the lab's productivity.

You've joked that your lab is productive in other ways, too.

Yes, there are a lot of babies in the lab! I tell my students, "There's no one time better than another to have a child so if you're ready to have one now, do it."

Is this the voice of experience talking?

Yes, I have two sons. I had the first when I was in medical school and the second during my residency. There were definitely times when it was hard. But I managed with a very supportive spouse, Andrew Bent, a UW professor of plant pathology. Having babies then was a challenge, but it worked out very well: my oldest son is now in medical school and my youngest is in college.

How do you feel about nurturing graduate students?

Helping people through all aspects of their career development is a big part of what I do and I will do even more of it as director of the MD/PhD program. Mentoring is a very intense interaction that you don't get with other aspects of your work. To me, it's one of the most enjoyable parts of the job. Graduate students come to our labs without a lot of experience and they leave as scientists who generally know what they want for their future. It's an amazing transition to watch.

What do you like to do in your spare time?

We go on a good back-packing trip each year. I joined a back-packing club when I was 11, and now my kids lead back-backing trips. I enjoy walking my dogs - one's a Golden Retriever-Poodle mix and the other is a Standard Poodle. I read fiction and have been getting back to photography after many years. I used to be a serious viola player, so I play some and enjoy concerts.

This article appears in the fall 2011 issue of Quarterly.