Peter Shrager, PhD, is a professor of Neuroscience and of Pharmacology & Physiology at the University of Rochester Medical Center (URMC). He received his undergraduate degrees in liberal arts and electrical engineering at Columbia and completed his PhD at the University of California, Berkeley. He went on to do postdoctoral research in physiology and immunology at Duke University. In 1971, Shrager came to URMC to work in what was then the Department of Physiology. His research interest is in axonal conduction, particularly ion channel structure, function, and localization, and with a special focus on the interaction between neurons and glial cells resulting in myelination.
What led you to neuroscience?
As an undergraduate, while I was studying electrical engineering, I found my interest shifting to biomedical research. At first, I considered biomedical engineering, but this field was in its infancy, and there were few opportunities in graduate programs. At UC Berkeley, I switched from engineering to the biophysics program, which was part of a group that included UCSF and UC Davis. I began my research with Alfred Strickholm at UCSF, working on conduction in giant axons of an invertebrate, the crayfish. When Strickholm left, I moved back to Berkeley and joined the lab of Robert Macey, continuing my experiments on crayfish axons. In those days, we knew that voltage-dependent ion channels were at the root of excitability, but we had no idea how they were built or how they worked. In my thesis work, I combined protein physical chemistry and electrophysiology to do some very early investigation in this area, and I continued with this for many years after coming to Rochester. In between, I did postdoctoral research with Peter Lauf and Daniel Tosteson at Duke, where I worked on red cell antigens and enhanced my skills in protein chemistry and immunology.
How did you make your way to the University of Rochester?
In 1971, I was recruited to the University of Rochester by Paul Horowicz, a muscle electrophysiologist who had been at Duke, and had just become chair of Physiology here. Horowicz rapidly built a large group with an interest in ion channels and related areas, making UR an internationally known center in the field. The atmosphere at Rochester was incredibly interactive and supportive. It fostered some real innovation in our field. This was an era prior to the cloning of ion channels, but major results came from combinations of electrical and chemical approaches. In those days, one could not purchase the equipment needed for these studies. We had to design and build everything ourselves. Thus, most people in the field (and it was quite small, perhaps 50 labs worldwide) came from a background in either physics or engineering. With my UR colleague, Clay Armstrong, we were among the first electrophysiologists to utilize computers to run experiments and analyze data in neuroscience. The computers we used were the size of telephone booths, consumed several kilowatts of power, and cost (in 1975) $10,000. Nonetheless, they replaced photographic film, and increased by an order of magnitude, the rate of experimentation and accuracy in recording.
What is your research focus and how has it evolved?
My research focus began with structure-function in ion channels, and I pursued this field for about 20 years at UR. I then became interested in ion channel localization. Evidence had accumulated that these channels were not uniformly distributed in the surface membrane, but rather tended to be clustered at specific sites. This was especially important in myelinated axons, where action potential generation occurred at small gaps in the myelin sheath, known as nodes of Ranvier. At first, we used novel approaches in electrophysiology to probe channel distribution. We next turned to optical recording techniques that made it possible to follow signals propagating along single axons. This led us into an analysis of conduction in pathological situations, such as segmental demyelination, as it occurs in multiple sclerosis and Guillain-Barre syndrome. The electrophysiological approaches, though very informative, were too limited in spatial resolution. We were then very fortunate. S. Rock Levinson at the University of Colorado had just made the first antibody against sodium channels, and he agreed to collaborate with us. Using immunofluorescence, we followed sodium channel localization in both normal myelinated fibers and after initiating demyelination. These channels were clustered very tightly at nodes, and were present at much lower densities elsewhere. We found that, during both development and remyelination, sodium channels clustered in the axon membrane exactly under the tips of elongating myelinating Schwann cells. As these Schwann cells grew longitudinally, the axonal sodium channels moved along with them, eventually joining a cluster from an adjacent Schwann cell. This is the mechanism by which nodes of Ranvier form. We have since investigated many associated phenomena in both normal development and pathological situations. We have also expanded our interests to several other ion channel types. Our research now is largely collaborative. We have an especially active project with James Salzer at NYU, investigating a key transcription factor necessary for myelination, and the clinical conditions that result from changes in its expression. I also work with several people here at UR, and, over the years, I have found the atmosphere here to be especially conducive to collaboration. Our faculty is very approachable, and the fact that both clinical and basic science are essentially housed under one roof fosters this interaction.
Your reputation with students precedes you. How do you connect and engage with students?
I have always enjoyed teaching. It has always been in my life: my father was a teacher. When I first came to Rochester I taught both medical and graduate students – today I just teach graduate students. My approach, however, has always been fundamentally the same. I teach students to analyze cellular phenomena through problem solving, rather than rote memorization. I have been teaching cellular neuroscience in one form or another for over 50 years. I use the problem solving approach because that is what one does in research, and I believe that is the only way to learn how electrical signaling works. I am also responsible for the course Biology of Neurological Disorders that was originally started by Robert Joynt, the former Chair of Neurology, and Dean of the School. We meet once/week, and in each session we focus on a different disease. In the first hour, we have a lecture on the clinical aspects of the disease. During the second hour, we cover the basic pathophysiology, and in the final hour, students present pre-assigned papers. We cover a wide range of neurological disorders, from the more molecular to the more psychiatric and cognitive. We also span the range from developmental disease states to those predominant in the aged. With over 20 faculty participating, it is difficult to organize, but it is always rewarding to see how the experience benefits our students. Our graduate student body is far more diverse than it was when I first came to Rochester, both in gender and in ethnicity. In both the classroom and the laboratory, I find our students to be exceptional in their ability to learn and to conduct research in neuroscience.
This article originally appeared in NeURoscience | Vol 16.