The Division of Pediatric Neurology faculty provide research in a variety of areas. Specific research interests include:

Dr. Kathy Mathews began with using genetic linkage, then a putative mouse model, to identify the gene causing facioscapulohumeral dystrophy. She closed her laboratory in 2000 due to increasing clinical and administrative demands, and my current academic efforts have been focused on improving the quality of care for patients with neuromuscular disease. She has maintained an active interest in the impact of molecular genetics on neuromuscular diseases (diagnosis, pathophysiology and treatment). She has served on NIH and CDC working groups to define the direction of research on neuromuscular disease in the future. She has become increasingly involved in collaborative clinical research efforts, many of which are laying a groundwork for clinical trials.

Dr. Mathews is currently a co-PI (with Paul Romitti, PhD) on the Iowa MDSTARnet project, a CDC sponsored, multi-center Duchenne/Becker Muscular Dystrophy surveillance and epidemiology project. She is a co-PI on one project of the University of Iowa’s NIH funded Wellstone Center, directed by Kevin Campbell, PhD and Steve Moore, MD, PhD. This project involves defining the phenotypes of patients with FRKP mutations and will extend nationwide. This clinical project was a key component of this successful NIH application. She is also the Iowa PI in the United Dystrophinopathy project; a genotype-phenotype study headed by Dr. Kevin Flanigan at the University of Utah and recently funded by the NIH.

Dr. Dan Bonthius does research on central nervous system development and the factors that can disrupt it. He focuses his research on two neuroteratogenic agents: alcohol (fetal alcohol syndrome) and lymphocytic choriomeningitis virus (congenital LCMV infection). Investigating the cellular and molecular mechanisms underlying alcohol- and LCMV-induced injury to the developing brain, the behavioral consequences of these injuries, and therapeutic agents to minimize or reverse the injuries.

The development of gene therapy for neurological diseases. In particular, he is exploring the use of viral gene therapy vectors for the treatment of Alexander Disease, a devastating genetic disease of the pediatric brain.

Dr. Alexander Bassuk focuses research on congenital defects of the nervous system, especially neural tube defects, familial epilepsy, neurogenetics, neural stem cell biology.

His laboratory is interested in understanding the basic mechanisms underlying both normal and disordered development of the nervous system. His laboratories approach to these issues includes investigating the genetics of human neural tube defects (NTDs) and familial epilepsies, and elucidating the biology regulating neural stem cell development. The techniques used in our laboratory include genome wide linkage analysis (GWA), association studies, comparative genomic hybridization (CGH), copy number variation (CNV) analysis, transgenic mouse production, and cell culture. As part of our studies we have collected DNA samples from over 2000 patients and family members with congenital nervous system malformations, and several large families with autosomal recessive epilepsy syndromes.

Dr. Steven Stasheff conducts research on the fundamental physiologic mechanisms of neurologic diseases affecting the visual system, and 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 my 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. Bahri Karacay conducts research on the abnormalities of developing nervous system caused by two neuroteratogenic agents; alcohol, (fetal alcohol syndrome) and lymphocytic choriomeningitis virus (congenital LCMV infection). Development of gene therapy for neuroblastoma, a childhood cancer of the nervous system and Alexander Disease, a disease of cerebral white matter that affects children.

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