Biography
Current research in the Smith lab:
- The effect of cytokines on neurite growth in the central nervous system.
- Identification of cell signalling mechanisms mediating the neuroprotective and/or regenerative effects of pharmacological agents.
Area of research
My general research interest is in elucidating molecular mechanisms mediating repair of the damaged central nervous system.
Axon regeneration
Axon regeneration failure in the mature central nervous system (CNS) can be attributed to two main factors; 1) loss of intrinsic regenerative potential in mature neurons, 2) enhanced inhibitory environment following axonal injury. The main focus of my research is to explore potential mechanisms mediating regenerative capacity in the mature and developing CNS by targeting both environmental inhibitory influences as well as intrinsic mediators of regenerative capacity. Current studies involve the use of both in vitro and in vivo model systems, coupled with genetic and pharmacological approaches to elucidate cellular and molecular mechanisms underlying loss of regenerative capacity in the injured mature CNS.
Neurodegeneration
Another area of my research focuses on degeneration of neuronal cell bodies and axonal degeneration in models of traumatic brain injury. In this regard, a proportion of my previous research has been geared at understanding the molecular signals that govern cell survival and cell death in models of Parkinson’s disease (Smith et al. 2003 and Smith et al. 2006) and following traumatic brain injury (Kalia et al. 2003). Building upon this work, current studies aim at exploring mechanisms mediating loss of axonal processes in both in vitro and in vivo model systems.
It is my hope that this line of work will provide some insights into molecular mechanisms that could aid in the development of effective treatment strategies for several neurological and psychiatric disorders.
Selected publications
Smith PD, Mount MP, Shree R, Callaghan S, Slack RS, Anisman H, Vincent I, Wang X, Mao Z, Park DS. (2006) Calpain-regulated p35/cdk5 plays a central role in dopaminergic neuron death through modulation of the transcription factor myocyte enhancer factor 2. J Neurosci. 26(2):440-7.
Smith PD, Crocker SJ, Jackson-Lewis V, Jordan-Sciutto KL, Hayley S, Mount MP, O’Hare MJ, Callaghan S, Slack RS, Przedborski S, Anisman H, Park DS. (2003) Cyclin-dependent kinase 5 is a mediator of dopaminergic neuron loss in a mouse model of Parkinson’s disease. Proc Natl Acad Sci U S A. 100(23):13650-5.
Kalia SK, Lee S, Smith PD, Liu L, Crocker SJ, Thorarinsdottir TE, Glover JR, Fon EA, Park DS, Lozano AM. (2004) BAG5 inhibits parkin and enhances dopaminergic neuron degeneration. Neuron. 44(6):931-45.