Burré Laboratory

Burré Lab Website

Burré Laboratory researchers study the mechanisms by which synaptic dysfunction triggers neurological disorders, focusing on the molecular mechanisms underlying synucleinopathies, including Parkinson’s disease, Lewy body dementia and Munc18-1-linked encephalopathies, in order to identify rescue strategies to delay or prevent pathogenic events. They apply a repertoire of disease models, which range from purified proteins and primary neurons to C. elegans and genetic mouse models, utilizing biochemical, biological and biophysical approaches.

Lab Projects

Dysfunction of STXBP1 in infantile epileptic encephalopathies

Principal Investigator:

The American Epilepsy Society and The Epilepsy Foundation

Mutations in STXBP1 are associated with Ohtahara syndrome, West syndrome, and Dravet syndrome. These syndromes are devastating infantile epileptic encephalopathies, characterized by progressive cerebral dysfunction, leading to cognitive, sensory and/or motor function deterioration due to unremitting epileptic activity. STXBP1 is a neuronal protein which is essential for neurotransmitter release. Since 2008, more than 30 de novo mutations have been identified in the STXBP1 gene, which are linked to these seizure disorders. Yet, the impact of mutations on STXBP1 function is unknown. The goal of this grant is to investigate how disease-linked mutations in STXBP1 affect its function in vitro.

Function and Dysfunction of Synucleins at the Synapse

Principal Investigator:

Leon Levy Foundation

The interplay and contribution of α-, β- and γ-synuclein to the pathogenesis of diseases termed synucleinopathies is unknown. Synucleins are abundantly expressed in the brain, where they  localize to synaptic terminals. Yet, despite 25 years of research, their normal function remains unknown. Similarly, it remains enigmatic how synucleins trigger devastating diseases such as Parkinson’s disease (PD), dementia with Lewy bodies (DLB), multiple system atrophy, frontotemporal dementia, and Gaucher’s disease. The goal of this grant is to investigate the interplay of α-, β- and γ-synuclein with regard to their physiological functions and pathological activities.

Aging increases the aggregation-prone cytosolic pool of α-synuclein

Principal Investigator:

American Parkinson Disease Association

Age is the biggest risk factor for developing Parkinson’s disease (PD), and α-synuclein pathology is a causal link to PD. In nerve terminals, α-synuclein cycles between a membrane-bound pool on synaptic vesicles and a cytosolic pool, and we have previously found that membrane-binding of α-synuclein protects it from aggregation. Yet, our understanding of age-dependent dynamics in intracellular α-synuclein pools is poor. The goal of this grant is to determine age-dependent changes in the subcellular localization of α-synuclein that lead to α-synuclein aggregation and pathology, and to identify triggers for this altered localization.
 

A small molecule approach to rescuing protein misfolding in infantile epileptic encephalopathies

Principal Investigator:

Sanofi Innovations Awards Program, Sanofi

The goal of this grant is to reverse the specific dysfunctions caused by mutant STXBP1 using a small molecule approach.

Molecular mechanisms of Munc18-1 linked infantile seizure disorders and rational rescue strategies.

Principal Investigator:

NIH/NINDS (3/1/2017-2/28/2022)

The goal of this grant is to identify the disease mechanism underlying Munc18-1 linked infantile epilepsies, and to develop rescue strategies to combat pathogenic events.

Stabilization of synaptic vesicle-bound alpha-synuclein to reduce alpha-synuclein aggregation and pathology in Parkinson’s disease

Principal Investigator:

The Michael J Fox Foundation (01/01/2019 – 12/31/2020)

The purpose of this grant is to generate mutants of alpha-synuclein that raise its membrane-bound state and to characterize these mutants regarding function and dysfunction.

Weill Cornell Medicine Helen & Robert Appel Alzheimer’s Disease Research Institute 413 E. 69th St. New York, NY 10021