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Research

Consortium Grad Makes New Discovery

Philip Horner

Philip Horner, lab manager
and surgeon Don Maris,
and post-doc who pioneered
the netrin-1 study Dr. Audrey Petit

In the 1990s, Dr. Philip Horner was learning his trade at one of the Reeve Foundation's first Consortium labs. "The thing we were doing at the Consortium, which was unusual then in scientific research, was learning how to work together," says Horner. "Can multiple labs do projects together? We put our best ideas together. The goal wasn't that we cure spinal cord injury. The goal at that time was: Can you take a developmental biology lab, a physiology lab, a molecular lab, can you get them to work together on one project and functionally integrate?"

This kind of sharing and cooperation is still one of the goals of the Reeve Foundation's Consortium labs around the world.

Making a New Discovery
Today, Horner runs his own lab at the University of Washington in Seattle. It is here that he and his team, made an important discovery in the fall of 2007. The research is based on a serendipitous discovery by a very talented post-doc, Dr. Audrey Petit. Together with they found that the netrin-1 molecule was repelling growth building cells from the site of a spinal cord injury (PNAS Nov. 6, 2007, vol 104, no. 45, 17837-17842 – Audrey Petit, Drew L. Sellers, Daniel J. Liebl, Marc Tessier-Lavigne, Timothy E. Kennedy, and Philip J. Horner)

If you get a hole in your skin, the skin cells fill it in. When you have a spinal cord or a brain injury, a lesion forms. It's basically a hole with blood in it. Scientists have tried unsuccessfully to bridge that gap, but what Horner's paper asks is why is that hole there? Why does it persist?

The answer is netrin-1. If you block this molecule from getting to the injury site, adult neural progenitor cells linger in the hole. "You need to fill in that hole," explains Horner. "Break the polarization of the scar and the hole so that the adult stem cell can remodel the lesion site. Remodel it in such a way that it's permissible towards re-growth."

Back to the Beginning
As a young man Horner was happy working in a hardware store. "I was kind of a wild kid," he says. "I didn't really want to go to college." But one day his dad and brother – both engineers -- just signed him for a full load of engineering courses.

Once he got to college, he found the two subjects he hated most in high school, biology and chemistry, were now much more interesting. "A light bulb came on," Horner admits. "And then through college I had the idea that I wanted to somehow build a career around this interest in biology and chemistry. My family has a history of Alzheimer's disease, so I had in the back of my mind, ‘Well, this seems like a good career path for me, maybe I'll go on and become a neurologist, or I'll go find a cure for Alzheimer's disease.'"

"I was enjoying myself a little too much at college," Horner tells on himself. "So I missed all of the graduate school applications except for a couple of schools." Horner wanted to work with fetal tissue. "At the time, in the 80's, everyone thought we'd cure everything with fetal tissue, even Alzheimer's Disease. People started to think that maybe fetal tissue transplants would work." The program he would get accepted to at Ohio State was studying spinal cord injury and fetal tissue transportation.

"It was really the end of my graduate career that Christopher Reeve had his riding accident, and I was at that time still looking at Alzheimer's labs for a post-doc," says Horner, "but just after that event occurred, I ran into Rusty Gage at the Society for Neuroscience meeting. (Gage is a founding member of the Consortium, and runs one of the labs.) I was overwhelmed by his lecture, I thought it was really impressive and he had incredible tools, genetic tools for manipulating the nervous system, manipulating axon growth. I looked at him and thought, 'Here's a guy who hadn't really studied spinal cord injury, and I thought if I could take his tools and apply it to spinal cord injury with my knowledge that I gained at Ohio State. I could really do something!'"

Horner hadn't completely sold himself on switching from Alzheimer's to the spinal cord, but at that same meeting Gage told him that Christopher Reeve and his foundation was putting together this Consortium, and he was going to need a trainee to be a point person. The timing was absolutely perfect, says Horner. "He looked at me, and I looked at him, and I said ‘Let's do this!'"

Philip Horner

The lab is a busy place.

The New Way to Research
The Consortium and its members, past and present, are helping to change the culture of scientific research. "Remember, in the spinal cord field it takes three years to get a paper published because the experiment takes so long, so the climate was very competitive," explains Horner. "I'd go to a meeting with my first graduate advisor and he would say, ‘Don't tell so and so this, don't tell so and so that.' You couldn't afford to be open if you wanted to keep your career moving forward. Telling anybody about your work was dangerous."

Horner stresses that his recent discovery of the function of netrin-1 was a collaboration. One of the scientists working on the project was a fellow Consortium associate who he's kept in touch with through the years.

"We would spend twelve hours a day eating McDonalds in the operating room doing these experiments together," remembers Horner about the old days. "And what was good about those experiments was that you learned how to work together. We cross-trained too. Plus, we got to do all these thought experiments in our head.  We'd think, this is a cool experiment, but what could we do that would be more exciting? Later in life we matured into our own labs. Now some of us are writing grants together."

Private vs. Government Funding
"I wouldn't be sitting here with this paper," emphasizes Horner. "We wouldn't be here with some of the constants we've come out with without privatized foundation funding."

"The Reeve Foundation, the Paralyzed Veterans of America, and the Neilson Foundation (who funded the netrin-1 research) all continue to fund this new research (that would not qualify for government funding)," says Horner. "Those are the guys that help really innovate and give you the opportunity. If we didn't have that mixture of funding, this work certainly would never have happened."

Now What?
"We just need to get the first step," says Horner, "and that's to fill the hole and that's what we're really pushing for. Can we get some tissue regeneration in the cord? Good or bad that's the goal for this year. If we can get that to happen then we'll start working on phase two, which is then getting it to be useful regeneration."

"I realize now," says Horner, "that sometimes you can't put science to work for you, but have to go where science takes you, and I think that's what I learned from the Consortium."

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Continue Christopher Reeve's LegacyPhoto by Timothy Greenfield-Sanders