Jeff Petruska, Ph.D.,
Ben Harrison, Ph.D.
By: Sam Maddox
Jeff Petruska is a scientist at the Kentucky Spinal Cord Injury Research Center at the University of Louisville. He got the science bug early on: "I had a pet frog that died. Instead of burying it, my mom said, 'Well, let's dissect it. I'll show you the things on the inside.' She took it apart and showed me where the heart was and how the muscles attached to things and all this stuff that you don't see from the outside. From that point on, third grade, I loved biology."
He's still looking inside. After grad school at the University of Florida, Petruska became a post-doc Associate in Lorne Mendell's laboratory at SUNY-Stony Brook, one of six labs in the Reeve Foundation International Research Consortium on Spinal Cord Injury. "I was fascinated by the electrophysiology they were doing there, how neurotrophins affected the physiology and anatomy of neurons. I loved it." He didn't anticipate the impact this would have on his career.
"The Consortium is an amazing entity; it trains its Associates in how science is really being done now. You have to be multidisciplinary. You have to collaborate. The Consortium is about working across disciplines, across many labs."
The Associates from the Consortium labs meet formally twice a year. "We spent a lot of time together. This was absolutely invaluable to me. I formed a cadre of people I trust. I know their science. I know their approach. I've gotten calls to help them design experiments, and I do the same thing, reaching out to them when I need help."
As an Associate, Petruska spent a lot of time in the Consortium labs of Reggie Edgerton (UCLA), Mary Bunge (Miami), and Fred Gage (Salk). "I learned to speak the language of their experiments, and they learned mine," he said. "I learned more from the Consortium than I would have by going on to a second post-doc. I set up a number of collaborations that have been invaluable as I moved on and started my own lab." Petruska was attracted to the Kentucky SCI program because he says it reminded him of the Consortium model. "I interviewed with a bunch of places that all had really great stuff going on. But this place felt the closest to that collaborative model."
Petruska's current work evolved from a Consortium assignment he began at the Mendell lab. "The question I asked is: How do adult neurons that are not injured extend new branches of their axons? Of those that are injured, some extend axon branches using regeneration. But some axons that are not injured grow and change their connections too. It's called collateral sprouting. So I put this idea in front of the Consortium, all of the principal investigators, the advisory panel -- they said 'do it.' That was a powerful expression of faith and confidence and very meaningful to me as a postdoctoral fellow."
Once set up in Louisville, Petruska put a team together. "I'm not a molecular biologist. So that's where I went to Laurence Moon, who at the time was the Associate in Mary Bunge's Consortium lab at the Miami Project. He had just completed his own micro-array [screening for genes] experiment, which was outstanding. He compared the genes in the central nervous system neurons that could regenerate after injury with those that could not regenerate."
Petruska recruited his own post-doc, molecular and cellular biologist Ben Harrison. The university already had a computational/bioinformatics expert, Eric Rouchka, to develop tools to analyze huge datasets. "Together we've gone from a broad data set to one that identifies, for the first time, the specific genes necessary for collateral sprouting."
The genes needed to turn on regeneration are not the same as those that control sprouting. Is there clinical relevance? "Possibly. We think that a lot of the plasticity observed after TBI and SCI is not actually regeneration. It might be collateral sprouting. This can be good or it can be bad; recovery after stroke involves collateral sprouting of non-injured neurons. But so does autonomic dysreflexia [blood pressure disregulation]. In AD you want to stop collateral sprouting. But you don't want to stop it in TBI if it's helping to recover certain functions."
Using genetically modified animal models to explore the difference between the two processes, Petruska is hoping eventually to manipulate the genes for a therapeutic advantage.