Arthur Brown
Principal Investigator
Why I Became a Scientist
For as long as I can remember I have been driven to find out how things work. As a child, I constantly asked my parents and teachers “how and why” questions. How do batteries work? How do motors work? Why do compass needles point north? And when it came to the workings of the human body, there were no end to my questions. Within the human body there is probably no greater mystery than the workings of the brain. The brain is not only the master controller of all the other organs of the body, but it also allows us to think, to emote and ponder our own existence. It makes us what and who we are. I love being a neuroscientist – I get paid for investigating one of the greatest mysteries of life.
Research Summary
Recovery after spinal cord injury depends on the balance of pro- and anti-regenerative forces
Spinal cord injury is a catastrophic event that is a major health care issue, causing lifelong disability. In the USA and Canada, more than 12,000 spinal cord injuries occur annually, and ~275,000 people live with permanent, serious disabilities due to SCI. Since spinal cord injury typically occurs in young adults, it represents a lifelong burden to the patient and a socioeconomic challenge to our society. Currently, there are no effective treatments for spinal cord injury. The body’s response to spinal cord injury includes processes that promote regeneration and processes that not only inhibit regeneration but actually increase damage. The balance of these pro– and anti-regenerative forces determines the final clinical result. We have three major areas of research focused on identifying and testing strategies to tip the balance of power away from damaging processes and towards productive healing. Our research program includes anti-inflammatory strategies, cellular therapies and gene therapies designed to harness the good part of the body’s response to spinal cord injury while limiting the bad parts of this natural response to injury.
Research Questions
What role does inflammation play in spinal cord injury?
Mechanical injury to the spinal cord is followed by an inflammatory response that leads to a great deal of damage that gets worse with time. However, inflammation also triggers processes such as wound healing that are of significant benefit. Most of the damaging effects of inflammation are carried out by a subset of white blood cells called neutrophils. In collaboration with the Weaver and Dekaban laboratories, we are investigating the use of a monoclonal antibody that blocks these cells from entering the injured cord. This experimental treatment has shown remarkable success in preclinical animal studies and is being further developed.
Can stem cell transplantation be used to improve outcomes from spinal cord injury?
The capacity for repair in the injured spinal cord is greatly impaired because the mature central nervous system, with rare exceptions, is unable to generate new neurons or to regenerate axonal connections. Cell transplantation has therefore emerged as a promising treatment for spinal cord injury. We have investigated the use of adult stem cells derived from bone marrow in a mouse model of spinal cord injury. We have found that these stem cells promote repair of the spinal cord by promoting the repair and rescue of damaged tissue and by altering the expression of scar genes to promote regeneration.
Regeneration in the nervous system is hindered by the expression of genes that block nerve growth. What regulates the activation of these inhibitory genes?
The absence of axonal regeneration after spinal cord injury has been attributed to nerve-repelling molecules in the damaged myelin and scar. These inhibitory molecules in the scar are produced by reactive astrocytes responding to the injury. However, astrocytes have also been shown to produce molecules that promote nerve growth. We have identified a master control gene that regulates the balance between the anti- and pro-regenerative genes activated after spinal cord injury. We are currently devising strategies to block this master control gene so as to maximize the expression of pro-regenerative genes and minimize the expression of anti-regenerative genes after spinal cord injury.
Education
- Doctorate in Medical and Molecular Genetics, University of Toronto
Training
- Postdoctoral training in Neurodegeneration at the Institut du Cancer, Montreal, QC
- Postdoctoral training in Neurodevelopment at the Salk Institute, San Diego, CA
Awards
- Doctorate in Medical and Molecular Genetics, University of Toronto
- Postdoctoral training in Neurodegeneration at the Institut du Cancer, Montreal
- Postdoctoral training in Neurodevelopment at the Salk Institute, San Diego, CA
- Heart and Stroke Foundation of Canada, New Investigator’s Award,
- CIHR - SOX9 regulation of scar production after spinal cord injury
- CIHR - Leukocyte integrins as targets for neuroprotective strategies after spinal cord injury
- Morton Cure Paralysis Fund - Identifying SOX9 inhibitors to promote regeneration after spinal cord injury
- International Fund for Paralysis Research - Regeneration and recovery after spinal cord injury in a SOX9 knockout mouse
Publications
Complete List of Published Work in MyBibliography
Contact Info
Email: abrown@robarts.ca
Administrative Assistant: Darlene Goodine
Phone: 519-931-5251
Email: dgoodine@robarts.ca
