Nicholas Katsanis, Ph.D.
Human Geneticist, McKusick-Nathans Institute of Genetic Medicine

Bardet-Biedl syndrome is a rare inherited disorder characterized by a diverse set of symptoms, including vision loss, obesity, extra digits and mental defects. Yet the research that Nicholas Katsanis is performing on the disease may have implications for millions of people with much more common diseases, such as type 2 diabetes and schizophrenia. Katsanis recently sat down with Dome to talk about his work.

Why do you focus on Bardet-Biedl syndrome?
For several reasons. First, the disorder has huge clinical variability. You see two kids within the same family—one of them is profoundly affected; one of them, almost unaffected. That, to me, as a human geneticist, says that in addition to the primary genetic defects, there are going to be other genes to modify the severity of the disease. In fact, our lab was the first to demonstrate that this is the case.

Second, nearly every cell in the body seems to be affected by Bardet-Biedl syndrome. So my question is, how can one survive with this? Also, I thought if we could understand why some kids are affected so severely, we might get a profound insight into cell biology in a broad sense. This has also proven to be true, because we now understand that Bardet-Biedl syndrome is caused by a defect of the cilia [short, microscopic hairs attached to the cell], and our lab is trying to understand what these cilia do. It’s a big mystery. But we do know that if things go wrong with cilia, people are faced with broad medical challenges.

The third reason is because many of the problems in patients with cilia defects overlap clinically with common complex disorders—type 2 diabetes, schizophrenia, obesity. We’ve recently discovered that the same kind of molecular dysfunction that occurs in Bardet-Biedl syndrome also holds true in a small fraction of type 2 diabetes patients. Still, there are millions of diabetics out there, and if I can explain 1 percent, that’s 7 million souls. That’s a frightening number.

Is this what drives you? I mean, you’re a Ph.D.—you don’t see patients.
I do not see patients. The one thing that drives me is sheer and utter curiosity. I’m a purist in that sense. The other thing that drives me—and forgive me if this sounds a little sappy—is to leave the world a little better than I found it.

We should all be so fortunate.
I’ve been very fortunate. It can be seen as a selfish thing, because when you acquire new knowledge, it buys you a little bit of immortality. But there’s also a big altruistic component. I come from a family in Greece where my first cousin became very ill and died from a horrible neurodegenerative genetic disease. I was young when I saw what this did to the entire family, and it left a big impression. I thought, people shouldn’t have to go through this. I’ve known that I wanted to do genetics since I was 14 or 15 years old. I’ve been very single-minded about getting to my goal.

I don’t know if I’m there, but I’m in a good spot. I have wonderful colleagues. We can sit here and think about interesting questions, think about ways to address them and hope that maybe 0.00001 percent of the experiments we perform will make a difference. That would be the ultimate gratification.

Do you work collaboratively with say, ophthalmology?
I work collaboratively with everybody. Although my training is in human genetics, I believe that we should not mold our questions to our expertise, but that our experimental design should be dictated by the questions. When the question is taking us somewhere we don’t know, we have this wonderful device called the telephone. It can go to, say, the Ross Building where there’s a world expert on exactly the experiment I want to do. I would say that better than 90 percent of the time, I’ve been able to pick up the phone or send an e-mail, and say, ‘Hi, Joe Schmo, I am Dr. Nobody who works down here, but I have this really cool question. Can we get a cup of coffee?’ Then six weeks later, you send a student across the street who learns something new and you become intellectually richer as a person, a little bit more informed as a scientist. Some of the stuff that we published in this evolutionary paper [see sidebar], what? Are you kidding? I’m very proud. This is the first paper I’ve ever published, and probably the last, where you will find big differential equations. I suck at math! But my good colleague, Dave Cutler [formerly with the IGM], who unfortunately just moved down to Atlanta, he’s a wizard in mathematics and statistics. We love collaborations.

Can you give me a run-down of the disciplines you collaborate with?
OK. Neuroscience, developmental biology, various forms of clinical science, from nephrology to pediatrics to ophthalmology, statistics that take various forms, to very hard-core biochemistry to anatomy to all of them, I think! I know all these people because the diseases I work with are so diverse. I’m very proud of the fact that I work with problems relevant to nearly every single branch of the NIH. That's because we’re dealing with a series of defects that affects potentially every tissue and every system. Mostly we focus on the kidney, the eyes and the brain, but we’re now expanding to the muscle, the heart and the peripheral nervous system.

The really great thing is, I couldn’t tell you what I’ll be doing next year! Don’t have the foggiest! And I like to be that way. I enjoy surprise very much, I enjoy the challenge from the students and fellows. It truly makes my day when a student or a colleague walks in my office and says, ‘Hey, I was looking at this, and I did this really quick and dirty test and I found so and so. I think we should invest three years and do this.’ I say, ‘Sure, why not?’ And that’s how it goes. Every year, something a little different. And every year there’s a discovery in a slightly different way.

If you look at the mix of people in my lab, they all come from vastly different disciplines, from synthetic chemistry to neuroscience and everything in between. We are all wired in a specific way, molded by our educational background: A developmental biologist thinks a little differently than a human geneticist. It’s when the two collide that you actually come up with pretty cool things and you stand a chance to break down dogma.

So we’re just plodding along to the unknown and I couldn’t tell you what I’m gonna hit next. But all I can tell you is, more likely than not, it’s gonna be really exciting.

–Reported by Mary Ellen Miller