Where Are They Now?
January 7, 2004

Life after the Reeve Foundation Research Consortium on Spinal Cord Injury.

This is an excerpt from the Reeve Foundation publication Walking Tomorrow.

With cutting-edge skills and a strong sense of purpose, young researchers are emerging from the Reeve Foundation Research Consortium on Spinal Cord Injury deciding to dedicate their professional lives to reversing the toll of spinal cord injuries. Some even attribute their career choice to their experiences in the Consortium.

Seven senior scientists comprise the multi-disciplinary Consortium, meeting regularly to pool their skills and research and to plan joint experiments. Each scientist selects at least one postdoctoral research fellow to be a Consortium associate, who will attend all Consortium meetings and work closely with the other associates on inter-laboratory experiments. There have been 29 Associates since the Consortium was formed in 1995. Sixteen have rotated out of the Consortium and nine now lead their own spinal cord injury research teams.  "The Consortium has set up Centers of Excellence where younger people are exposed to scientists who are really good at their particular approach to spinal cord research," says Guy McKhann, M.D., professor of neurology and neuroscience at Johns Hopkins Medical School.

Dr. McKhann, who serves on the Consortium Advisory Panel that evaluates the work of the group, says the associates also benefit from interacting with the other members of the Consortium and viewing spinal cord injuries from different perspectives. Being a CRF associate is "a unique introduction to the field, and it is starting to pay off," he says.

Among the latest Consortium alumni to have set up research laboratories are Aileen J. Anderson, Ph.D., at the University of California-Irvine; Philip J. Horner, Ph.D., at the University of Washington in Seattle; and Keith E. Tansey, M.D., Ph.D., at the University of Texas-Southwestern Medical Center in Dallas. Dr. Aileen J. Anderson was an associate from 1997 to 2001 under Carl Cotman, Ph.D., director of the Institute for Brain Aging and Dementia and a professor in the departments of neurology and psychobiology at UC-Irvine. Today she manages the Consortium's core animal laboratory at UC-Irvine, where members run collaborative experiments. In her own work, she specializes in two areas: the immune response to spinal cord injuries and the therapeutic potential of one type of human stem cell.

Dr. Aileen Anderson

As a graduate student at UC-Irvine, Dr. Anderson looked at how messages from the sensory system cause changes in the brain, a process known as activity-dependent plasticity. She eventually found that some influence brain plasticity also are active in Alzheimer's disease and some forms of Down's syndrome. Deciding to study this relationship further, she completed her Ph.D. with Dr. Cotman, studying this area. In 1996, she was at Harvard still exploring brain degeneration when Dr. Cotman asked her to attend a Consortium meeting in San Diego. Dr. Anderson recalls answering: "I'll go, but I am not doing spinal cord research." She returned to Boston from the meeting "enormously impressed" by the extent of the collaboration and the accomplishments of the Consortium members and associates.

She returned to UC-Irvine in 1997 as Dr. Cotman's Consortium associate and gradually abandoned her Alzheimer's work. She began her new research by looking at what happens in the immune system when the spinal cord is injured. Her focus is the complement cascade, a series of molecular events that activate immune cells. This reaction helps the body ward off illness and infection but also causes inflammation that can destroy healthy cells and worsen an injury. She recently has shown that the complement is fully activated after spinal cord injury, and she traced how that process unfolds in rodents. Dr. Anderson now is testing how mice lacking some of the genes that trigger the complement cascade fare after a spinal cord injury, and how external factors like exercise affect the immune system. She believes that scientists eventually will be able to harness the immune response to treat spinal cord injuries.

In her stem cell work, Dr. Anderson studies human neural progenitor cells, the parent cells that spawn neurons and all of the other cell types in the brain and spinal cord. The progenitor cells may be easier to use therapeutically than embryonic stem cells, which are more primitive and must be "coaxed" to become neurons and their supporting cells. She plans to test whether transplants of neural progenitor cells can repair the damage from spinal cord injuries in mice bred to reduce the chances their bodies will reject the stem cells.

Dr. Philip J. Horner did not intend to become a spinal cord researcher. He expected to be a civil engineer until he discovered that he disliked engineering and enjoyed biochemistry. Eventually, he chose to study degenerative brain disorders because his family has a history of Alzheimer's disease.

While he completed his master's and doctorate degrees in physiology at Ohio State University, Dr. Horner's biochemistry skills earned him a training spot in the Spinal Cord Injury Research Center there. He learned to use animal models of spinal cord injuries and saw how nerve cells could be coaxed to regenerate after such injuries. "I became passionate about researching spinal cord injuries," he remembers. "I also thought they might be easier to cure than degenerative diseases."

After graduate school, he wanted to acquire the sophisticated tools of molecular biology by working under Consortium member Fred Gage, Ph.D.,  [Link to PDF - opens in new window - CRF to provide]  professor in the Laboratory of Genetics at The Salk Institute in San Diego. Dr. Gage invited him to join his research team and to become a Consortium associate. Dr. Horner was surprised when he was asked to present a paper on gene therapy and spinal cord injury at his first Consortium meeting.

"The great minds in the field were treating me like a long-time colleague," he explains. "I went from having one world-class mentor to having six more. Too often," adds Dr. Horner, "research is done in a vacuum. If you have a great idea, you don't tell anyone." He says that the Consortium shows the "far-reaching benefits" of working openly with other scientists.

In the Gage laboratory from 1996 to 2000, Dr. Horner contributed to the discovery that the brain makes new cells throughout life. The Gage team identified glial cells, a type of stem cell deep in the brain of adult rodents that spawns new cells. Dr. Horner found that these cells, which support, feed, and protect neurons and account for forty percent of the central nervous system, also are replaced in the spinal cord. He wondered why so many glial replacements were needed. He hypothesized that people's ability to recover from a spinal cord injury or to avoid degenerative neurological diseases might hinge on how well they produce new cells.

For the last two years in his own laboratory at University of Washington in Seattle, Dr. Horner has been searching for the characteristics of the glial replacement mechanism. One challenge is to develop ways to identify and analyze the glial parent, or progenitor, cells that give rise to new glia. He is also trying to pinpoint how glial cells respond to brain and spinal cord injuries, especially how these cells create scars that pose both a physical and chemical barrier to the regeneration of nerve cells.

"Most people have focused on the impact of the scar and how to dissolve it," he says. "We look at how the scar is made. We believe that it forms through the birth of new cells that then "choose" a glial fate. We may have an opportunity to go in and change the fate of those newborn cells."

Dr. Tansey and Dr. Edgerton
Dr. Keith E. Tansey also found that the talent and the technology of the Reeve Foundation Consortium elevated his research. "I got exposure to the leaders in the field and a broad spectrum of disciplines, from neuro-immunology to electrophysiology," says Dr. Tansey. From 2000 to 2002 he was the Consortium associate of V. Reggie Edgerton, Ph.D., a physiologist at UCLA.

Dr. Tansey's career has had dual tracks since his undergraduate days at Stanford, where he simultaneously earned a bachelor's degree in biology and a master's degree in biomechanics. He completed a joint M.D. and Ph.D. program at the University of Texas-Southwestern Medical Center, specializing in neurology and neuroscience. How the spinal cord sparks movement especially fascinated him and continues to inspire his research. "Some 300 motoneurons control a single muscle," Dr. Tansey says. "How do the brain and spinal cord activate them? How is the spinal cord organized in the first place, and how does it reorganize after an injury?"

After a neurology residency and fellowship at Washington University School of Medicine in St. Louis, he went to the Edgerton laboratory, where he explored the effects of locomotor training on rats with incomplete spinal cord injuries. In this type of training, animals are suspended over a treadmill so that their hind limbs move in a stepping pattern. In time, this regimen "teaches" the spinal cord below an injury to activate the muscles needed to walk, restoring some function. Previous animal studies had looked only at complete injuries.

"Had it not been for the Consortium," he says, "I would not have been able to finish the work." As evidence, he notes that to create his animal models he collaborated with Dr. Anderson, who used equipment from the Consortium animal core laboratory at UC-Irvine.

Another associate in the Cotman laboratory helped him use the Consortium's gene chip core laboratory to identify the many differences in gene activity between the trained animals and the untrained controls. And, a new robotic device developed at UCLA enabled Dr. Tansey to check for improvements in the animals' gate over the course of the experiment. For the past year, Dr. Tansey has been setting up a regional center at the University of Texas that will feature comprehensive services for spinal cord patients and sophisticated research facilities. The interdisciplinary Spinal Cord Injury Center is a partnership between Parkland Medical Center and the University of Texas. The new Center will include a special intensive care unit for spinal cord patients, an inpatient rehabilitation unit, and an outpatient clinic. The Center also will house both animal and human spinal cord research laboratories. Patients will have access to clinical trials based on
promising therapies from animal studies.

Dr. Tansey will head the Center, which represents the merger of his medical practice and his spinal cord research, allowing him, as he puts it, "to move bench-top discoveries to bedside interventions."
"I was never satisfied with just doling out existing treatments to patients," he says. "I have always wanted to help."

Similarly, the Reeve Foundation Consortium was organized with an eye toward the future. "We recognized that the next generation of spinal cord researchers would need rigorous training and would have to be willing to dedicate themselves to solving the many complexities posed by a spinal cord injury,"says Susan Howley, Executive Vice President and Director of Research at the Reeve Foundation. "The associates truly are one of the Consortium's greatest strengths."