Department of Biology
Man with all of his noble qualities still bears in his bodily frame the indelible stamp of his lowly origin.
Charles Darwin
The goal of the Casey lab is to understand the transcriptional regulation of a class of genes involved in the formation of the early vertebrate body plan. Patterning events such as the establishment of neural tissues require a series of signal transduction events that lead to the transcription of a set of genes. Few of the details of transcriptional regulation in vertebrate development have been deciphered. However, the ability to generate transgenic frogs has revolutionized the field, allowing rapid analysis of promoter function in a large number of embryos. This technique, along with embryology, traditional biochemical and molecular assays, and expression screens now enable us to define the factors required for regulation of genes involved in early vertebrate development.
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RESEARCH NEWS FEATURE: ELENA CASEY
The Donoghue Laboratory examines the development of the cerebral cortex, the largest and most complex portion of the mammalian forebrain. A battery of molecular, cellular, biochemical, and organismal approaches is used to examine the forces that shape the proper formation of the cortex. For example, current studies focus on how the proliferation of cells in immature cellular zones is controlled in development so that the mature cortex contains the appropriate number of cells. In addition, once cells have stopped dividing, we are interested in the regulatory programs that control their subsequent differentiation in more mature compartments. Together, we are interested in the coordination of cell genesis and cell differentiation in order to produce an integrated neural structure that has the proper cells present in the proper proportions. Mouse models (mutant, transgenic) are used for examining the function of particular genes in vivo and in vitro.
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My laboratory is interested in understanding mechanisms of seizure generation and in seizure protection. A major tool in this investigation is the use of calorie restriction, high fat diets, or both to alter seizure threshold. The hypothesis driving our investigations is that brain energy utilization has a general role in determining seizure threshold and severity. While various specific defects may be responsible for the particular characteristics of each of the many epileptic syndromes (for example, alterations in ion channels, transmitter receptors or re-uptake mechanisms), the broad effectiveness of dietary manipulation, particularly caloric restriction, suggests a generic role for energy. Our approach is to manipulate diet, especially fat and carbohydrate content, determine seizure threshold and severity, and determine relationships to receptors and transporters for gulcose and fat-derived metabolites.
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RESEARCH NEWS FEATURE: DOUG EAGLES
My research group has pioneered study the study of the neuorpeptide NAAG over the past two decades. We pursue the mechanisms through which NAAG chemically communicates information among cells. Our lab identified the receptors that this peptide activates and cloned two enzymes that mediate its inactivation. Currently, we are determining the role of endogenous NAAG at identified synapses, characterizing peptidases that hydrolyze NAAG in the nervous system, and developing novel compounds that inhibit these peptidases. These compounds decrease the rate of inactivation of the peptide and enhance its activity in the nervous system. My research group applies these compounds in animal models of important human disorders including chronic and inflammatory pain perception, schizophrenia, and excitotoxicity associated with traumatic brain injury. Our aim is to develop new therapies for these disorders.
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RESEARCH NEWS FOCUS: JOE NEALE