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Jeff Bronstein, M.D. Ph.D.

 

My lab has 2 main focuses:  1)  Determining how does the environment cause PD and   2)  Developing novel therapies using zebrafish.   We have found that a number of commonly used pesticides alter the ubiquitin proteasome system (UPS) and aldehyde dehydrogenase (ALDH) activity.  Both of these processes have been implicated in the pathogenesis of PD.  We also study the underlying molecular mechanisms that these pesticides act.  For example, ziram and other dithiocarbamate fungicides inhibit E1 ligase that disrupts the targeting of damaged proteins to the UPS.  Importantly, we have also found that exposure to ziram can increase one’s risk of developing PD by 3 fold in humans (studies led by Dr. Ritz) and administration of ziram to cell cultures and mice recapitulates many of the important aspects of PD.

 

We are also interested in using zebrafish to identify and study new disease modifying therapies for PD.  We have developed a transgenic zebrafish that expresses human a-synuclein in neurons, which leads to abnormal morphology, synculein aggregation, UPS inhibition, and apoptotic cell death.  We have used this model to identify drugs that mitigate this toxicity and identify how these drugs work.   We have also developed a transgenic zebrafish that expresses GFP in tyrosine hydroxylase (TH) expressing neurons.  We have systematically killed clusters of these TH-GFP neurons using a 2-photon laser to determine which of these cells control swimming and the escape response.   These fish are also being used to identify toxins that kill these cells.

 

 

 

 

                                                                                                

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Research
Allan Wu, M.D.
Jeff Bronstein, M.D. Ph.D
Carlos Portera-Calliau, M.D. Ph.D