Research Overview

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.

About Paul Rosenberg

Paul Rosenberg received his BA from Yale College, and his MD and PhD degrees from Albert Einstein College of Medicine. He completed an internship at University Hospital, Boston, a neurology residency through the Harvard-Longwood Neurological Training Program and a fellowship in cellular neurobiology at Boston Children's Hospital.

Researcher Services

Researcher Areas

  • Mechanisms of Homeostatic Sleep Regulation
  • Molecular Mechanisms of Brain Injury
  • Pathogenesis of brain injury in premature infants
  • Physiology and Pathology of Glutamate Transporters in the Central Nervous System

Research Departments

Researcher Programs

Researcher Centers

PUBLICATIONS

  • Rimmele TS, Rosenberg PA (2016) GLT-1: The elusive presynaptic glutamate transporter. Neurochem Int 98:19-28.
  • Petr GT, Sun Y, Frederick NM, Zhou Y, Dhamne SC, Hameed MQ, Miranda C, Bedoya EA, Fischer KD, Armsen W, Wang J, Danbolt NC, Rotenberg A, Aoki CJ, Rosenberg PA (2015) Conditional deletion of the glutamate transporter GLT-1 reveals that astrocytic GLT-1 protects against fatal epilepsy while neuronal GLT-1 contributes significantly to glutamate uptake into synaptosomes. J Neurosci 35:5187-5201.
  • Kabakov AY, Rosenberg PA (2015) GLT-1 transport stoichiometry Is constant at low and high glutamate concentrations when chloride Is substituted by gluconate. PLoS One10:e0136111.
  • Frederick NM, Bertho J, Patel KK, Petr GT, Bakradze E, Smith SB, Rosenberg PA (2014) Dysregulation of system xc(-) expression induced by mutant huntingtin in a striatal neuronal cell line and in R6/2 mice. Neurochem Int 76:59-69.
  • Elitt CM, Rosenberg PA (2014) The challenge of understanding cerebral white matter injury in the premature infant. Neuroscience 276:216-238.
  • Back SA, Rosenberg PA (2014) Pathophysiology of glia in perinatal white matter injury. Glia 62:1790-1815.
  • Petr GT, Schultheis LA, Hussey KC, Sun Y, Dubinsky JM, Aoki C, Rosenberg PA (2013) Decreased expression of GLT-1 in the R6/2 model of Huntington's disease does not worsen disease progression. Eur J Neurosci 38:2477-2490.
  • Petr GT, Bakradze E, Frederick NM, Wang J, Armsen W, Aizenman E, Rosenberg PA (2013) Glutamate transporter expression and function in a striatal neuronal model of Huntington's disease. Neurochem Int 62:973-981.
  • DeSilva TM, Borenstein NS, Volpe JJ, Kinney HC, Rosenberg PA (2012) Expression of EAAT2 in neurons and protoplasmic astrocytes during human cortical development. J Comp Neurol 520:3912-3932.
  • Volpe JJ, Kinney HC, Jensen FE, Rosenberg PA (2011) The developing oligodendrocyte: key cellular target in brain injury in the premature infant. Int J Dev Neurosci 29:423-440.