Jacqueline Burre, Ph.D.
Assistant Professor of Neuroscience, WCMC
The Jacqueline Burre laboratory at Weill Cornell Medical College is interested in early pathological events at the neuronal synapse that trigger neurological disorders and neurodegeneration.
Neurons communicate via release of neurotransmitters from presynaptic terminals. This requires intact functioning of the protein expression and trafficking machinery, of mitochondria to meet a synapses’ need for energy, of the proteasome/ubiquitin system and lysosomes to clear aged and misfolded proteins, and of the synaptic vesicle cycle to mediate continuous neurotransmission. Much evidence points to presynaptic terminals as initiation site for neurodegeneration in diseases such as Parkinson’s disease, Alzheimer’s disease, and Huntington’s disease, where synaptic dysfunction has been suggested to precede neuron death and to occur long before neuropathological symptoms become apparent. Yet, virtually nothing is known about processes involved.
My lab is interested in early pathological events at the synapse which trigger neurological disorders and neurodegeneration. We will approach this topic by:
- investigating the dysfunction of synucleins at the synapse, a protein family implicated in Parkinson’s Disease, Alzheimer’s Disease, multiple system atrophy, and dementia with Lewy bodies;
- investigating the dysfunction of Munc18 at the synapse with regards to Ohtahara syndrome (early infantile epileptic encephalopathy) and mental retardation with non-syndromic epilepsy;
- by an exploratory screen to identify other yet-unknown mechanisms triggering synaptic dysfunction and degeneration in various diseases.
To address these aims, we will employ an array of cutting-edge technologies, including biophysics, biochemistry, cell biology, imaging, and mouse models of neuropathology.
Investigating the dysfunction of synucleins and Munc18 at the synapse, as well as screening mouse models of neurodegenerative diseases for synaptic changes will identify pathological events happening early in the progression of the various diseases. We envision that defining early pathological events at the synapse will provide new avenues for preventing and/or treating neurodegenerative diseases in humans.
- Burré J*, Vivona S*, Diao JJ, Sharma M, Brunger AT, Südhof TC. Properties of native brain α-synuclein. Nature, 498: E4 (2013). [*equal contribution]
- Diao JJ*, Burré J*, Vivona S, Sharma M, Südhof TC, Brunger AT. Native α-synuclein induces clustering of synaptic vesicle-mimics via binding to phospholipids and synaptobrevin-2/VAMP2. eLIFE, 2: e00592 (2013). [*equal contribution]
- Burré J#, Sharma M, Südhof TC#. Systematic mutagenesis of α-synuclein reveals distinct sequence requirements for physiological and pathological activities. The Journal of Neuroscience, 32: 15227-15242 (2012). [#corresponding authors]
- Sharma M, Burré J, Südhof TC. Proteasome Inhibition Alleviates SNARE-Dependent Neurodegeneration. Science Translational Medicine, 4:147ra113 (2012).
- Sharma M, Burré J, Bronk P, Zhang Y, Xu W, Südhof TC. CSPα knockout causes neurodegeneration by impairing SNAP-25 function. The EMBO Journal, 31: 829-841 (2011).
- Sharma M, Burré J, Südhof TC. CSPα promotes SNARE-complex assembly by chaperoning SNAP-25 during synaptic activity. Nature Cell Biology 13: 30-39 (2011).
- Burré J*, Sharma M*, Tsetsenis T, Buchman V, Etherton MR, Südhof TC. α-Synuclein promotes SNARE-complex assembly in vivo and in vitro. Science 329: 1663-1667 (2010). [*equal contribution]
- Burré J#, Beckhaus T, Schägger H, Corvey C, Hofmann S, Karas M, Zimmermann H, Volknandt W. Analysis of the synaptic vesicle proteome using three gel-based protein separation techniques. Proteomics 6: 6250-6262 (2006). [#corresponding author]
- Burré J#, Beckhaus T, Corvey C, Karas M, Zimmermann H, Volknandt W. Synaptic vesicle proteins under conditions of rest and activation: analysis by 2-D difference gel electrophoresis. Electrophoresis 27: 3488-3496 (2006). [#corresponding author]
- Morciano M*, Burré J*, Corvey C, Karas M, Zimmermann H, Volknandt W. Immunoisolation of two synaptic vesicle pools from synaptosomes: a proteomics analysis. Journal of Neurochemistry 95: 1732-1745 (2005). [*equal contribution]