Scientific Accomplishments
- Genetic Engineering and Gene Therapy
As an early effort at what might be regarded as "genetic engineering" in the mid 70's, Richard Mullen of the Neuroscience Program of the IDDRC developed the skill of combining eight-cell-stage rodent embryos from genetically normal and abnormal in... [Read more]
- A Genetic Program Regulated by Neuronal Activity
In the 1980s Dr. Greenberg and his colleagues discovered that neuronal activity induces a genetic program that plays a key role in mediating brain development and function (Science 1986). Recent evidence from ... [Read more]
- A Signal Transduction Pathway that Promotes Neuronal Survival
During the development of the nervous system there is a critical balance between the survival and death of developing neurons. Neurons that form the proper connections received trophic support from their targets and survive whereas neurons t... [Read more]
- Adverse Effect of Cranial Radiation on Cognition
Observations reported in the mid-1980's described the occurrence of cognitive impairments subsequent to prophylactic cranial radiation in children with leukemia. Waber and her collaborators in this IDDRC followed up on this initial observation (
[Read more] - Adverse Effect of Maternal Phenylketonuria on Offspring
Stimulated by the original observations of Mabry and his colleagues in the early 1960's, Dr. Harvey Levy in this IDDRC had a central role in the study of the effect of untreated maternal PKU during pregnancy on the offspring (Transplacental E... [Read more]
- Adverse Effects of Low Lead Level Exposure
Beginning in the mid-1970's, the IDDRC at Children's Hospital became the site of a multidisciplinary longitudinal study of the adverse effects of concentrations of lead below previously accepted exposure levels. Drs. Alan Leviton and David Belling... [Read more]
- Animal Models of Neurological Disease and of Cerebral Malformations
In the late 1970's and early 1980's the mutant mouse, Spastic, was studied to determine the origin of its neurological syndrome of tremors and abnormal righting behavior. An electrophysiological analysis suggested a deficit in inhibition at the le... [Read more]
- Behavior and Genetics
Between approximately 1980 and 1990, major insights into the relationships between the sex chromosomes and behavior were established by interactions in the Children's Hospital IDDRC between investigators in the Genetics Program and in the Clinical... [Read more]
- Clinical, Cellular and Molecular Aspects of Brain Injury in the Premature Infant
The two major forms of brain injury in premature infants are periventricular leukomalacia (PVL) and periventricular hemorrhagic infarction (PHI), a form of severe germinal matrix/intraventricular hemorrhage (GMH-IVH). Research in this IDDRC from t... [Read more]
- Congenital Heart Disease, Cardiac Surgery and Brain Development
Of the 30,000 infants born annually in the United States with congenital heart disease, more than one-third will require cardiac surgery in the neonatal period. Dramatic reductions in surgical mortality for such deep hypothermic cardiac surgery wi... [Read more]
- Deprivation Amblyopia and the "Critical Period"
Several investigators of the IDDRC (Duffy, Snodgrass, Burchfiel, Nature, 1976) showed that the GABA antagonist, bicuculline, can reverse the inhibition of a significant percentage of the inactive nerve cells in the visual cortex in an ex... [Read more]
- Duchenne/Becker Muscular Dystrophy
This research, which developed most actively in the mid-1980's and continues vigorously to the present, has been led in a most remarkable way by Dr. Louis Kunkel, Director of the Genetics Program and Associate Director of this IDDRC. Duchenne musc... [Read more]
- Genetic Imprinting in Human Genetics
A series of studies led by Dr. Marc Lalande, formerly of this IDDRC, delineated the regions on chromosome 15q11-13 that are mutated in Angelman syndrome (AS) and Prader-Willi syndrome (PWS). Lalande’s research also identified candidate genes... [Read more]
- Genomic Analysis of Brain Tumors
Medulloblastomas and other embryonal brain tumors, the most common malignant brain tumors of childhood, have a 40-50% overall mortality. Survivors typically live with profound developmental and neurological disabilities, largely due to toxic thera... [Read more]
- Infantile Hydrocephalus and CSF Dynamics
In the early 1970's, Cutler, Lorenzo, Barlow and their colleagues (Brain, 1968; Brain, 1970; Arch. Neurol., 1974) carried out fundamental studies of infants with hydrocephalus which provided much of the current knowledg... [Read more]
- Manipulation of Human Chromosomes by Dyes and Cell Sorting
The study of human chromosomes was pursued actively by Dr. Samuel Latt over the many years of his tenure in the Children's Hospital IDDRC (Ann. Rev. Biophys. Bioengr., 1976; Ann. Rev. Gen., 1981; Banbury Report, Cold S... [Read more]
- Mechanisms that Restrict Axon Regeneration after Injury
Damage to the developing or mature nervous system can be devastating due to the limiting ability of central nervous system axons to regenerate if they are severed. Two laboratories in the IDDRC (Benowitz and Z. He) have made outstanding cont... [Read more]
- Molecular Approaches to Down's Syndrome and Alzheimer's Disease
In 1984 and 1985, Kurnit and coworkers reported that Down's syndrome cells from developing lungs and hearts are more adhesive to each other than are the cells of normal controls (Am. J. Med. Gen., 1985; Proc. Natl. Acad. Sci., 19... [Read more]
- Neural Progenitors, Cellular Transplantation and Gene Therapy
Beginning in 1991, a major new area of research in this IDDRC has been the study of neural progenitor or “stem cells.” This research has included landmark studies of cell fate determination (i.e., identification of external facto... [Read more]
- Neuroepidemiology and Neuropathology of Periventricular White Matter Injury of the Premature Newborn
Periventricular white matter injury is the most important neuropathological substrate for the subsequent neurological disability, i.e., cerebral palsy and cognitive deficits, observed in premature infants. In 1973 Leviton and Gilles began a classi... [Read more]
- Neuronal Migration During Brain Development
In the 1970’s Rakic, Sidman and co-workers in this Center defined the mechanisms of neuronal migration during development of the mammalian cerebral cortex (J. Comp. Neurol., 1972; Science, 1974; J. Com... [Read more]
- Retrograde Transport by Nerve Cells
The important observation of neuronal retrograde transport of horseradish peroxidase in the central nervous system by the LaVails in 1972 had a profound impact on neuroanatomy and neurobiology in the decades following the description of this pheno... [Read more]
- The Development of Phospho-specific Antibodies as Key Reagents for Identifying Signal Transduction Pathways in the Brain
A critical early contribution of Greenberg and his colleagues was the development of phosphorylation site-specific antibodies to CREB. With these phospho-CREB specific antibodies, they were able to show that syna... [Read more]
- The Developmental Biology of Neural Tube Formation
Morphogenesis, the process of cellular organization, determines the form and function of the organs. A relatively few cellular behaviors are responsible for all of morphogenesis: these include changes in cell shape, motility, adhesion, proliferati... [Read more]
- The Modulation of Neuronal Excitotoxicity by Astrocytes
The important role of glutamate as the mediator of neuronal cell death by receptor-mediated mechanisms that involve the accumulation of cytosolic calcium was established primarily in the 1980's by work in several laboratories, including those of D... [Read more]
- The Use of Human Genetics to Identify Genes that Regulate Human Brain Development and Cognition
In the last decade investigators in this IDDRC have made exceptional use of human genetics to identify genes that cause neurological disorders. Dr. Christopher Walsh has been a pioneer in identifying genes that control the development and fu... [Read more]
- Visual Function in Children
Retinal disease that causes deficits of central and peripheral vision in infants and young children is a recognized accompaniment of several disorders in which mental retardation and developmental disability are also prominent and is an independen... [Read more]
- Wnts Signal Transduction and Nervous System Development
Wnts are secreted proteins that play critical roles in mammalian brain development and function. During embryogenesis, Wnt genes not only control brain patterning and neuronal progenitor proliferation and differentiation, but also regulate axon pa... [Read more]