University of Iowa Health Care Department of Ophthalmology and Visual Sciences

Education

• B.A. (Biology & Physics), University of North Carolina - Chapel Hill
• Ph.D. (Pharmacology), Duke University, Durham, NC
• M.D., Duke University School of Medicine

Post Graduate Education

• Intern (Pediatrics), Children's Hospital of Philadelphia
• Resident (Pediatrics), Children's Hospital of Philadelphia
• Resident (Pediatric Neurology), Children's Hospital, Boston
• Postdoctoral Fellow, (Retinal Neurophysiology), Howard Hughes Medical Institute, General Hospital, Boston
• Neuro-ophthalmology Fellow, Beth Israel-Deaconess Medical Center, and New England Medical Center, Boston

Certification

• Eligible for Certification, American Board of Pediatrics
• Certification in Neurology with Special Competency in Child Neurology: American Board of Psychiatry and Neurology, Inc.

Professional Affiliations

• Society for Neuroscience
• American Association of Pediatrics
• American Medical Association
• American Academy of Neurology
• Massachusetts Medical Society
• Child Neurology Society
• American Association for the Advancement of Science
• Association for Research in Vision and Ophthalmology
• North American Neuro-Ophthalmology Society

Steven F. Stasheff, MD, PhD received his B.A. in Biology and Physics summa cum laude from the University of North Carolina - Chapel Hill. His long-term interest in physiologic mechanisms of visual function already was evident in his undergraduate research on visual evoked potentials and the nonlinear processing of visual information. His MD and PhD were earned at Duke University, where he trained in electrophysiology, studying axon terminal hyperexcitability induced by in vitro epileptogenesis, under Wilkie A. Wilson, PhD. He then trained in pediatrics at Children's Hospital of Philadelphia, and in child neurology at Children's Hospital - Boston. He then completed a Neurological Sciences Academic Development Award (NSADA) under the mentorship of Richard H. Masland, PhD at Massachusetts General Hospital, investigating mechanisms of direction selectivity in a particular highly specialized ganglion cell of the retina. Simultaneously, he trained in neuro-ophthalmology under Jason J.S. Barton, MD, PhD, FRCPC at Beth Israel-Deaconess Medical Center and Thomas Hedges, III, MD at New England Medical Center. He joined the faculty of the University of Iowa in Pediatrics (Neurology) and Ophthalmology in the Fall of 2007.

His research interests center on the fundamental physiologic mechanisms of neurologic diseases affecting the visual system, and on the role that central nervous system (CNS) plasticity may play in both the pathogenesis and potential treatments for such disorders. Ongoing investigations aim to better understand electrophysiologic changes that occur in hereditary retinal degeneration, the most common inherited cause of blindness, and also a central feature of many neurodegenerative disorders in children and adults, including those that cause severe mental retardation, motor disability, and seizures.

Currently proposed therapies for these disorders hinge upon the assumption that even after photoreceptor degeneration, remaining retinal neurons would be able to normally process signals from rescued or replaced photoreceptors, or from direct electrical stimulation. In fact, significant anatomic reorganization of the inner retina occurs, and recent work in the Stasheff laboratory has identified corresponding physiologic changes that may involve mechanisms of developmental plasticity. The lab uses state-of-the-art multielectrode recording to monitor spontaneous and light-evoked activity simultaneously from 30-90 retinal ganglion cells in normal (wild type, wt) mice or those of the well-studied rd1 mouse model of retinal degeneration. Surprisingly, as the animal becomes blind, retinal ganglion cells do not simply drift into silence as might be expected. Rather, they develop striking hyperactivity (~10 times normal firing rate) that is sustained for many weeks. In fact, ganglion cells pass through at least three stages of activity: 1) normal spontaneous "waves" of correlated firing in early development; 2) increasing spontaneous activity with temporary preservation of light-evoked responses, selective for the OFF pathway; then 3) sustained hyperactivity that lasts for months, well beyond the loss of virtually all photoreceptors and light-evoked responses.

These striking alterations in inner retinal physiology tell us that in the rd1 mouse: 1) blindness occurs in the face of sustained ganglion cell hyperactivity; 2) these cells remain viable, thus amenable to various treatments, for an extended time despite this activity; 3) ON and OFF responses are differentially affected in early stages of degeneration. Since photoreceptor loss begins early and progresses rapidly in rd1 mice, it overlaps substantially with a normal developmental period of highly active synaptic plasticity. Thus, the lab now is comparing several transgenic mouse lines to explore the possibility that developmental plasticity may play an adaptive role in resculpting specific inner retinal circuits such as the ON and OFF pathways. Other avenues of investigation include dissecting changes in the neural code that rd1 ganglion cells use to communicate with the brain, exploring circuit-level and cellular mechanisms that underlie the alterations in their physiologic activity, and determining how widespread these changes are among other neurodegenerative diseases such as neuronal ceroid lipofuscinosis (NCL) and tuberous sclerosis (TS).

Dr. Stasheff's research is funded in part by a Scientific Award from the Child Neurology Foundation (CNF), a grant from the National Science Foundation to the Boston Retinal Implant Project, a Knights Templar Eye Foundation Pediatric Ophthalmology Research Award, as well as support from the Institute for Vision Research.