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Mark E. Dumont, Ph.D.
G protein-coupled receptors mediate cellular responses to a variety of sensory stimuli, hormones, growth factors, and neurotransmitters. We are interested in understanding the molecular mechanism by which the extracellular signal is transduced to G proteins in the cytoplasm, via seven-transmembrane receptors. We are using yeast genetics to study the regulation of signaling and the functional and structural properties of fungal and mammalian receptor mutants.
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Fred K. Hagen, Ph.D.
The formation of adult tissues and organ systems requires the integrated interactions of multiple cell types and cell surface molecules. Glycosyltransferases modify cell surface and secreted molecules and in a few cases are known to influence developmental processes like axon guidance, cell migration, cell signaling, and cell adhesion. A comprehensive functional genomics study on the role of glycosyltransferases in development is being complemented with detailed biochemical characterization of specific glycosyltransferases that are essential for development.
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David A. Pearce, Ph.D.
Batten disease is one of the more common childhood neurodegenerative diseases. Children with this disease usually suffer visual failure, psychomotor deterioration, seizures and premature death. Our research uses yeast and transgenic mice model systems to study the defects at the molecular level and cellular level to examine the associated properties and symptoms of this disease.
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Eric M. Phizicky, Ph.D.
Functional genomics is an approach to rapidly link biochemical activities with genes. Using an ordered array of yeast strains and proteins, we have used this approach to rapidly screen thousands of gene products and identified 16 associated with different biochemical activities. We are also studying tRNA splicing mechanisms in yeast and mammals, and why some bacteria have a functional tRNA splicing enzyme, but no apparent corresponding splicing requirement. Our future directions are to improve arrays and extend the functional genomic approach to different classes of activities.
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J.Edward Puzas, Ph.D.
Our current research effort is aimed at understanding the complex way bone and cartilage function. The maintenance of these tissues is critical for structural support as well as mineral homeostasis. A number of autocrine and paracrine factors are involved in this regulation. They include transforming growth factor beta, epidermal growth factor, basic fibroblast growth factor, BMP's, etc. Some of these factors also play a major role in pathological bone formation. Experiments aimed at reversing the bone loss that occurs in osteoporosis are currently underway in our laboratory.
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Randy N. Rosier, M.D., Ph.D.
Our research program involves investigation of the regulation of endochondral ossification, the formation of bone through mineralization of cartilage. This process is essential to bone formation and development in children, and is a fundamental element of fracture healing. Studies of growth factor effects, message regulation, synthesis and secretion, and receptor expression in chondrocytes in various stages of maturation are currently underway in our laboratory, and should provide insight into the control of mineralization, as well as some means of manipulating this process.
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Peter G. Shrager, Ph.D.
Ion channels in neurons are typically not distributed uniformly over the cell surface, but rather are clustered at high density at specific locations. Examples are sodium channels at nodes of Ranvier, potassium channels near paranodal regions, postsynaptic receptors, and calcium channels at presynaptic terminals. Neuronal function depends on the proper targeting of these channels to their correct destinations. We are investigating the mechanisms behind this early polarization of the neuron, as well as the associated ion channel targeting. We study both localization and function, combining molecular manipulations and immunocytochemistry with electrophysiology.
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