Robert E. B Burke, M.D.

Research Summary
The major goal of our laboratory is to identify the processes underlying the degeneration of neurons in Parkinson’s disease and related disorders. Parkinson’s disease is characterized by impaired motor control, including tremor, rigidity and slowness of movement. These disturbances are due to the loss of dopamine neurons of the substantia nigra of the midbrain. One of the current major hypotheses of this neuron loss is that it is due to programmed cell death (also known as apoptosis), a form of death in which genes intrinsic to the cell bring about its own destruction.

Programmed Cell Death in Dopamine Neurons
We have shown that apoptosis occurs during the normal development of dopamine neurons [Mol Cell Neurosci ‘93], and that it can be regulated by target interaction [PNAS ‘94]. We have also shown that apoptosis can be induced in dopamine neurons in models of parkinsonism. Therefore, one of our principal goals is to better define the molecular basis of apoptosis in dopamine neurons. We have a particular interest in identifying upstream mediators which may serve as therapeutic targets. An example of such is the MAPK signaling cascade, mediating phosphorylation of c-jun in models of apoptosis of dopamine neurons.

Neurotrophic Factors for Dopamine Neurons
During development, the number of neurons which die due to apoptosis is regulated by the availability of protein neurotrophic factors. We have shown that glial cell line-derived neurotrophic factor (GDNF) may be such a factor for developing dopamine neurons. Therefore, another of our research goals is to define the role of GDNF, and its mechanisms in supporting the viability of these neurons.

Dr. Burke's laboratory web site can be directly visited.

1. Burke RE, Antonelli M, Sulzer D. GDNF inhibits apoptotic death of postnatal substantia nigra dopamine neurons in primary culture. J Neurochem, 1998;71: 517-525.

2. Oo, TF, Henchcliffe C, James D, Burke RE. Expression of c-fos, c-jun and c-jun N-terminal kinase in a developmental model of induced apoptotic death in neurons of the substantia nigra. J Neurochem, 1999;72: 557-564.

3. Kholodilov NG, Neystat M, Oo TF, Lo SE, Larsen KE, Sulzer D, Burke RE. Increased expression of rat synuclein 1 in the substantia nigra pars compacta identified by mRNA differential display in a model of developmental target injury. J Neurochem, 1999; 73:2586-2599.

4. El-Khodor BF, Burke RE. Medial forebrain bundle axotomy during development induces apoptosis in dopamine neurons of the substantia nigra and activation of capsases in their degenerating axons, J Comp Neurol, 2002, 252:65-79.

5. Nunes I, Tovmasian LT, Silva R, Burke RE, Goff SP. Pitx3 required for development of the substantia nigra. Proceedings of the National Academy of Sciences USA, 2003, 100: 4245-4250.

6. TF, Kholodilov N, Burke RE. Regulation of natural cell death in dopaminergic neurons of the substantia nigra by striatal GDNF in vivo. Journal of Neuroscience, 2003, 23: 5141-5148.

1. Parkinson's disease research center at Columbia
National Institute of Neurological Disorders and Stroke
9/30/99-7/31/04

2. Apoptosis in substantia nigra
The theme of our investigations has been that the molecular pathways of programmed cell death (PCD) may be relevant to the pathogenesis of Parkinson's disease and allied disorders.
National Institute of Neurological Disorders and Stroke
9/30/94-8-31-05

The Michael J. Fox Foundation for Parkinson Research:
Member, Scientific Advisory Board
Co-Director, FastTrack Grants Program

apoptosis, developmental neurobiology, neurogenesis, neurotrophic factor, substantia nigra, biological signal transduction, gene expression, gene mutation, growth factor receptor, laboratory mouse, laboratory rat, transgenic animal