Columbia College, New York, Liberal Arts/Engineering, A.B.1962
Columbia Engineering, New York Electrical Engineering B.S.1963
University of California, Berkeley, Biophysics Ph.D.1969
Duke University, Durham, NC, Physiology 1969-1971
Cold Spring Harbor, NY, Molecular Biology 1995
University of Rochester Professor of Neurobiology & Anatomy 1996-present
University of Rochester Professor of Pharmacology & Physiology 1996-present
University of Rochester Professor of Biophysics 1993-1996
University of Rochester Professor of Physiology 1991-1996
University of Rochester Associate Professor of Physiology 1981-1991
University of Rochester Associate Professor of Physiology 1976-1981
University of Rochester Assistant Professor of Physiology 1971-1976
HONORS AND AWARDS:
Phi Beta Kappa
Tau Beta Pi (engineering)
Eta Kappa Nu (electrical engineering)
NIH Predoctoral Fellowship
NIH Postdoctoral Fellowship
NSF Postdoctoral Fellowship
NIH Research Career Development Award
First-Year Teaching Award and First-Year teaching commendations
Graduate Student Society Faculty Teaching Award
Fenn Mentor Award
The focus of this laboratory is on the interaction between neurons and glial cells, particularly myelinating glia. There are two primary areas of interest. Myelinated axons are not uniform, but rather consist of highly discrete domains, populated by unique proteins that confer specialized functional properties. The axon initial segment contains a high density of voltage-dependent sodium channels, as well as an associated set of cytoskeletal, adhesion, and matrix components, all of which allow this region to be the site of integration of synaptic inputs, resulting in the initiation of the action potential. Nodes of Ranvier have a similar composition, but reach that structure through a very different developmental mechanism. Nodes and adjacent paranodes and juxtaparanodes, along with compact myelin in the internodes, allow rapid, reliable, and efficient conduction of impulses. Our laboratory studies the molecular interactions between components of axons and Schwann cells (PNS) or oligodendroglia (CNS) that result in this unique structure. A wide variety of techniques, both molecular and electrophysiological are employed. A second major area is in recovery from spinal cord injury, and other traumatic diseases of the CNS. While axon regeneration can be robust in the PNS, it is markedly limited in the CNS. Among the mechanisms responsible, it has been demonstrated that remaining myelin at the injury site contains several proteins that are inhibitory to neurite outgrowth. This inhibition is mediated by receptors present on neurons that form a complex capable of initiating an intracellular signaling cascade. Using the optic nerve as a well-defined tract of CNS axons, and a series of mutant mice with the relevant proteins genetically deleted, a mechanism is sought through which regeneration can be improved. A question arose in the course of this work. Since these inhibitors and receptors are not likely to have evolved for this purpose, do they mediate other functions in the CNS? It has subsequently been shown that both the inhibitory proteins and their receptors are expressed by neurons at excitatory synapses. Further, in collaboration with Roman Giger, this laboratory has been investigating the role of this system in synaptic plasticity. Of particular interest, long term potentiation and depression, thought to be electrophysiological correlates of memory formation in the hippocampus, are regulated by this growth-inhibitory system. While this is studied for its intrinsic value in neurobiology, it is also relevant in spinal cord injury, where plasticity in remaining neurons is thought to play an important role in recovery of function.
Recent publications (2010-2012)
Raiker, S.J., Lee, H., Duan, Y., Koelzer, K.T., Shrager, P. and Giger, R.J. 2010 Oligodendrocyte-myelin glycoprotein and Nogo negatively regulate activity-dependent synaptic plasticity. Journal of Neuroscience 30:12432-12445.
Winters, J., Lenk, G., Giger-Mateeva, V., Shrager, P., Meisler, M. and Giger, R..J. 2011 Congenital CNS hypomyelination and reduced number of mature oligodendrocytes in the Fig4 null mouse. Journal of Neuroscience, in review.
Einheber, S., Maurel, P., Meng, X., Rubin, M., Lam, I., Mohandas, N., An, X., Shrager, P., Kissil, J. and Salzer, J. 2011 The 4.1B cytoskeletal protein is required for the normal domain organization of myelinated axons. Glia (online) 10-26-2012 DOI: 10:1002/glia22430.