Paul Rosenberg

I have had a longstanding interest in the role of glutamate transporters in maintaining glutamate homeostasis in the normal brain, and in abnormalities in glutamate homeostasis in acute and chronic neurodegenerative disorders. Early in my career, I discovered that glutamate transporters are critical in protecting neurons against the toxicity of glutamate, and that in the absence of glutamate transport, neurons are exquisitely sensitive to excitotoxicity. Based on this early work, I became interested in the contributions of astrocytes and neurons to glutamate homeostasis, mechanisms of cell death in the central nervous system, and the physiological and pathophysiological roles of nitric oxide. My work has led to a specific focus on the role of reactive oxygen species and reactive nitrogen species in the death of neurons and oligodendrocytes, and an appreciation of the importance of mobilization of free zinc following oxidative and nitrative stress. Current active projects in my lab include investigating the function of expression of GLT-1 in axon terminals, where it is the primary glutamate transporter, using multiple approaches including conditional knockout; understanding the synaptopathy that occurs in chronic neurodegenerative disease especially Huntington’s disease, and its relationship to glutamate dyshomeostasis; and the role of zinc in the white matter injury that is prevalent in the brains of premature infants. Finally, in collaboration with Dr. Larry Benowitz, we have uncovered a critical role for zinc in determining neuronal survival and regulating axon regeneration after optic nerve injury, and we are studying the molecular pathways by which zinc produces its effects in this and related paradigms of injury and neurodegeneration.