Paul Brehm, Ph.D.
Paul Brehm received his degree in zoology from the University of Wisconsin before entering the PhD program at UCLA where he trained with James Morin in marine biology and bioluminescence. Postgraduate training with Roger Eckert at UCLA and Yoshi Kidokoro at The Salk Institute focused on calcium channels and synaptic transmission. The next 10 years were spent as an Associate Professor in the Department of Physiology at Tufts Medical School in Boston and summers at the Marine Biological Laboratory at Woods Hole. In 1990 Brehm moved to Stony Brook University in New York where he served as Professor of Neurobiology and Behavior before assuming a position as Senior Scientist at the Vollum in 2007.
Summary of Current Research
Research in our lab utilizes the zebrafish animal model to explore the role of activity in regulating synapse development. In developing zebrafish the neuromuscular junction is readily accessible in vivo for both imaging and patch clamp electrophysiology. Our current approach utilizes mutant lines of fish that, due to defects in the motorneuron to muscle pathway, have profound motility dysfunction. In close collaboration with the Mandel lab we have assigned, by means of genetic mapping and sequencing, each signature defect to single point mutations in key proteins involved in synaptic function. This forward genetic approach provides a means to attenuate or alternatively amplify synaptic strength in order to determine the consequences on synapse formation and function. Examples of identified mutations include defective postsynaptic receptors, subsynaptic clustering protein, vesicle recycling protein, re-uptake transporter, calcium channels and the enzyme responsible for neurotransmitter synthesis. In many cases the associated motility defects in mutant fish lines are reminiscent of the human congenital myotonic and myasthenic syndromes. Remarkably, mutations in many of the mutant lines of fish are represented in humans and are directly causal to the human diseases. The zebrafish mutants offer the opportunity to determine the molecular underpinnings of the dysfunction and provide an experimental system with which to identify new therapeutic interventions.