Stephen J. Crocker, Ph.D.Associate Professor, Neuroscience
Chair, Graduate Programs Committee
|B.Sc.||University of King's College||Biology|
|Ph.D.||University of Ottawa||Pharmacology|
|Fellowship||Ontario Neurotrauma Foundation||Postdoctoral Fellowship|
|Fellowship||National Multiple Sclerosis||Advanced Postdoctoral Fellowship|
|Postdoctoral||Neuroscience Research Institute||Neuroscience|
|Postdoctoral||The Scripps Research Institute||Neuropharmacology|
|Postdoctoral||The Scripps Research Institute||Immunology|
|Name of Award/Honor||Awarding Organization|
|National Multiple Sclerosis Society Career Transition Award (2007-2011)||National Multiple Sclerosis Society|
|Dale McFarlin Travel Award||National Multiple Sclerosis Society|
|International Outstanding Young Investigator Award||ICCP|
|Bronze Medal||Ottawa Life Sciences Conference|
|Jock Cleghorn Award.||Canadian College of Neuropsychopharmacology (CCNP)|
|Summer Studentship||Parkinson’s Disease Foundation|
|Name & Description||Category||Role||Type||Scope||Start Year||End Year|
|American Association of Neuropathologists||Professional/Scientific Organization||Member||External||National||2005|
|American Society of Neurochemistry||Professional/Scientific Organization||Member||External||National||2003|
|Society for Neuroscience||Professional/Scientific Organization||Member||External||National||1999|
Stem cells; glia; metalloproteinases; cytokines; development; pathology; tissue culture.
My lab is interested in how the immune and nervous systems interact and how this balance is disrupted in diseases of the nervous system. The ultimate aim of our research program is to understand how the brain is injured during chronic inflammatory diseases of the nervous system, what regulates the ability of the brain to repair itself and how this knowledge might be used to promote brain regeneration and recovery.
Our current projects are examining role of the immune system in myelin pathology as it relates to diseases like Multiple Sclerosis (MS). In MS, the immune system mounts an inappropriate response against the coating of the nerve cells, called myelin. Myelin is critical for proper brain development and function. Hence, progressive myelin injury in MS can result in debilitation that can lead to permanent disability. The cause of MS is not known.
The purpose of this research is to understand how the nervous system responds to myelin injury and repairs myelin damage. Toward this goal, we have found that during an inflammatory attack that causes myelin damage the nervous system produces a protein called Tissue Inhibitor of Metalloproteinases-1 (TIMP-1). A function of TIMP-1 is to block key enzymes, called metalloproteinases, immune cells use to move into the brain tissues and can breakdown myelin. Our studies indicate that during inflammatory models of myelin injury TIMP-1 may be important in the regulation of immune cells called macrophages and microglia. As well, we determined that following myelin injury mice that lack TIMP-1 are also less able to repair their myelin. Accordingly, we propose to study two primary functions we believe to be important roles for TIMP-1: the control of macrophages and microglia following myelin injury, and the stimulation of myelin repair through promoting endogenous cells to rebuild the injured myelin.
It is interesting to note that although basal expression of TIMP-1 in the adult CNS is very low, it is readily and consistently induced in a variety of rodent demyelination models and increased in human individuals with acute demyelinating encephalomyelitis. However, levels of TIMP-1 are not elevated in chronic progressive forms of MS. It is plausible that chronic CNS inflammation, as occurs in MS, attenuates the ability of the brain to express TIMP-1 and the down-regulation of TIMP-1 may contribute to an individual’s susceptibility to developing CNS demyelination. Indeed, a paucity of TIMP-1 has also been reported with a chronic virus infection of the brain. Accordingly, we propose that study of TIMP-1 may represent an important system to understand MS-related CNS pathology.
Accepting Lab Rotation Students: Fall '19, Spring '20
Lab Rotation Projects
Research rotation projects in the lab will address the following questions:
Project 1. Does TIMP-1 participate in the regulation of CNS myelination?
Project 2. How does TIMP-1 regulate microglial responses to injury? Project 3. What controls astrocytic TIMP-1 expression?