| Modulation of the DAT/DJ-1 Interaction by Oxidative Stress |  |
Many researchers investigating the causes of Parkinson's disease have focused on the death of the brain cells that produce dopamine. While too little dopamine affects the mobility of people with Parkinson's, neurobiologist, Frank Lee, thinks too much dopamine can be just as destructive to brain cells.
"If there's too much dopamine, it can flood the system's ability to regulate it within a neuron," says Lee, an assistant professor at Simon Fraser University.
Lee is examining the relationship between two proteins involved in controlling how much dopamine brain cells produce. One of those proteins is called DAT, a dopamine transporter; and the other is DJ-1, which has been linked to familial forms of Parkinson's disease.
Other research groups have demonstrated that when mice are genetically engineered to lack DJ-1, DAT, the dopamine transporter, becomes increasingly active. The relationship between the two proteins appears to affect the transmission of dopamine. The interaction between those proteins and oxidative stress, a by-product of the process that occurs when cells use oxygen to generate energy, also appears central to the accumulation of dopamine.
Oxidative stress can produce toxic molecules that attach proteins and DNA, causing cell death. If Lee can confirm his characterization of the relationship among the proteins and oxidative stress, he believes researchers will be able to design a small, synthetic protein - called a peptide - to disrupt the interaction.
That, he hopes, would prevent the accumulation of too much dopamine within brain cells, and stop cell death.
Lee has been drawn to science ever since he watched What Will They Think of Next?, a popular science show that ran on Global Television when he was in public school. But when he was in graduate school, the role of dopamine began to capture his attention.
"Dopamine is fascinating to me because it's involved in so many different diseases, like Parkinson's disease, schizophrenia, and drug addition," Lee says.
He hopes by determining the role of different protein partners in regulating dopamine, his work will have broad applications to these other diseases as well.
As Assistant Professor at Simon Fraser University in the Faculty of Health Sciences, Dr. Lee is the recipient of the New Invesigator Award, through Parkinson Society Canada's Research Program. Total Award: $90,000 | 2010 - 2012
Dr. Lee received his BSc, MSc and PhD in Pharmacology from the University of Toronto. In 2001 he undertook post-doctoral training in Neuroscience at the Boston Children's Hospital at Boston's Harvard Medical School. Following his return to Toronto in 2004, he was a Senior Research Associate at the Centre for Addiction and Mental Health, and was the recipient of a Parkinson Society Canada Basic Research Fellowship from 2006 - 2008, training under the supervision of Dr. Fang Liu.
