Professor and Associate Chair, Anatomy and Cell Biology
Dr. Arthur Brown is a cell biologist researching brain and spinal cord injuries in the context of regenerative medicine. His lab researches natural responses to trauma — such as concussions — to optimize therapies by limiting inflammation and enhancing neuroplasticity.
The mammalian nervous system is composed of approximately 10 to the 11th different neurons each of which make very specific connections to other neurons or effector organs. Dr. Arthur Brown initially focused his research on the function of Eph receptors in axon guidance. Using embryonic stem cell technologies, he has engineered mice with altered Eph receptor expression and helped to prove the Eph receptors guide axons to their synaptic targets. The unexpected finding that one of the Eph receptor mouse mutants has a severe heart defect, allowed Dr. Brown to extend his studies of Eph receptors into the field of cardiac development and to demonstrate that the molecular control of cell movements and morphogenesis in the heart and developing nervous system are conserved.
More recently, Dr. Brown has combined his interests in neurological disease and neurodevelopment by initiating studies to address the role of embryonic genetic programs in regeneration and recovery from spinal cord injury. Dr. Brown has two major projects investigating therapeutic strategies to effect repair and regeneration after spinal cord injury. The first project is focused on manipulating gene expression in the injured spinal cord to up-regulate the expression of regeneration-promoting genes and to down-regulate the expression of regeneration-inhibiting genes.
The second project is based on the premise that stem cells, by virtue of their embryonic nature, may be able to rejuvenate and effect repair in the injured spinal cord. In this exciting project, bone marrow-derived stem cells are being evaluated for their potential therapeutic effect on regeneration and repair after spinal cord injury.
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
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About Arthur Brown
Dr. Arthur Brown is a cell biologist researching brain and spinal cord injuries in the context of regenerative medicine. His lab researches natural responses to trauma — such as concussions — to optimize therapies by limiting inflammation and enhancing neuroplasticity.
The mammalian nervous system is composed of approximately 10 to the 11th different neurons each of which make very specific connections to other neurons or effector organs. Dr. Arthur Brown initially focused his research on the function of Eph receptors in axon guidance. Using embryonic stem cell technologies, he has engineered mice with altered Eph receptor expression and helped to prove the Eph receptors guide axons to their synaptic targets. The unexpected finding that one of the Eph receptor mouse mutants has a severe heart defect, allowed Dr. Brown to extend his studies of Eph receptors into the field of cardiac development and to demonstrate that the molecular control of cell movements and morphogenesis in the heart and developing nervous system are conserved.
More recently, Dr. Brown has combined his interests in neurological disease and neurodevelopment by initiating studies to address the role of embryonic genetic programs in regeneration and recovery from spinal cord injury. Dr. Brown has two major projects investigating therapeutic strategies to effect repair and regeneration after spinal cord injury. The first project is focused on manipulating gene expression in the injured spinal cord to up-regulate the expression of regeneration-promoting genes and to down-regulate the expression of regeneration-inhibiting genes.
The second project is based on the premise that stem cells, by virtue of their embryonic nature, may be able to rejuvenate and effect repair in the injured spinal cord. In this exciting project, bone marrow-derived stem cells are being evaluated for their potential therapeutic effect on regeneration and repair after spinal cord injury.
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
| Present | Associate Professor, Western University ‐ Robarts Research Institute | |
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| Present | Associate Scientist, Lawson Health Research Institute ‐ Children's Health Research Institute (CHRI) | |
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| Present | Professor and Associate Chair, Research, Western University ‐ Department of Anatomy and Cell Biology | |
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Disciplines
Cell Biology and Anatomy