| | Principal Investigators
| Carolyn Beebe Smith, Ph.D. |
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Dr. Beebe Smith is Chief of the Section on Neuroadaptation and Protein Metabolism of the Intramural Research Program, National Institute of Mental Health, National Institutes of Health in Bethesda, Maryland. Dr. Smith received a Ph.D. from the University of London where she studied the chemical pathology of Alzheimer's Disease with David Bowen, for which she was awarded the Queen Square Prize. She did postdoctoral training with Louis Sokoloff at NIMH, and in 1986 became a Senior Investigator within the Laboratory of Cerebral Metabolism, NIMH. In 2000 Dr. Smith was awarded an honorary degree from the University of Linköping for her work developing an in vivo quantitative autoradiographic method for measurement of regional rates of cerebral protein synthesis in experimental animals. Dr. Smith and her team have adapted the method for use in human subjects with positron emission tomography. Dr Smith's group is currently studying mechanisms underlying brain dysfunction in fragile X syndrome and other neurodevelopmental disorders.
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| Research Interests |
The Section on Neuroadaptation and Protein Metabolism has a long-standing interest in understanding the regulation of protein synthesis in nervous tissue in vivo. To this end the Section has developed a quantitative autoradiographic method for the in vivo measurement of regional rates of cerebral protein synthesis. Studies in experimental animals indicate that regional rates of cerebral protein synthesis change during normal development and aging, in response to peripheral lesions and during slow wave sleep. The Section is currently studying genetic mouse models of neurodevelopmental disorders in which a dysregulation of cerebral protein synthesis may underlie abnormal phenotypes. In a mouse model of fragile X syndrome the Section has found that rates of protein synthesis in some brain regions are increased and that increases are reversed with pharmacological interventions, e.g. treatment with a Group I metabotropic glutamate receptor antagonist. The Section has adapted and validated the method for use in human subjects with positron emission tomography, and current studies will determine if findings in the mouse model of fragile X syndrome also apply to the human disease. If so, the PET method could provide a useful measure of clinical efficacy of proposed treatments.
Clinical Protocols:
Protocol Number: 06-M-0214
PET Measurement of Regional Rates of Cerebral Protein Synthesis in Subjects with Fragile X Syndrome
Protocol Number: 09-M-0123
Regional Rates of Cerebral Protein Synthesis: Effects of Sleep and Memory Consolidation |
| Representative Selected Recent Publications: |
- Bishu S, Schmidt KC, Burlin TV, Channing MA, Conant S, Huang T-J, Liu Z-H, Qin M, Unterman A, Xia Z, Zametkin A, Herscovitch P, Smith CB. Regional rates of cerebral protein synthesis measured with L-[1-11C]leucine and PET in conscious, young adult men: normal values, variability, and reproducibility. J Cereb Blood Flow Metab, 28:1502-1513, 2008 [pdf].
- Smith CB, Schmidt KC, Bishu S, Channing M, Bacon J, Burlin T, Qin M, Liu ZH, Xia Z, Huang T, Vuong BK, Herscovitch P. Use of acute hyperphenylalaninemia in rhesus monkeys to examine sensitivity and stability of the L-[1-11C]leucine method for measurement of regional rates of cerebral protein synthesis with PET. J Cereb Blood Flow Metab, 28:1388-1398, 2008 [pdf].
- Qin M, Smith CB. Regionally selective decreases in cerebral glucose metabolism in a mouse model of phenylketonuria. J Inherit Metab Dis, 30:318-325, 2007 [pdf].
- Qin M, Kang J, Burlin TV, Jiang C, Smith CB. Postadolescent changes in regional cerebral protein synthesis: an in vivo study in the Fmr1 null mouse. J Neuroscience, 25(20):5087-5095, 2005 [pdf].
- Smith CB, Kang J. Cerebral protein synthesis in a genetic mouse model of phenylketonuria. Proc Natl Acad Sci USA, 97:11014-11019, 2000 [pdf].
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