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Steven A. Thomas, MD, PhD
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Emeritus Associate Professor of Systems Pharmacology and Translational Therapeutics
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Department: Systems Pharmacology and Translational Therapeutics
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Contact information
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Department of Pharmacology
26 Room 103, John Morgan Building
3a 3620 Hamilton Walk
Philadelphia, PA 19104-6084
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26 Room 103, John Morgan Building
3a 3620 Hamilton Walk
Philadelphia, PA 19104-6084
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Office: (215) 573-4950
34 Fax: (215) 573-0838
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Email:
sathomas@upenn.edu
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sathomas@upenn.edu
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Publications
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Education:
21 9 A.B. 19 (Biochemistry) c
2d Princeton University, 1984.
21 f M.D. Ph.D 19 (Neuroscience) c
2f University of Michigan, 1991.
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Permanent link21 9 A.B. 19 (Biochemistry) c
2d Princeton University, 1984.
21 f M.D. Ph.D 19 (Neuroscience) c
2f University of Michigan, 1991.
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54 The roles of neurotransmission in development, neurophysiology and behavior
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1b RESEARCH TECHNIQUES
66 Mouse molecular genetics, electrophysiology, behavioral studies, molecular expression analysis
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18 RESEARCH SUMMARY
25b Broadly, the lab studies the development and physiology of the mammalian brain. One goal is to define the systems that contribute to specific behaviors, and to understand the mechanisms that underlie these behaviors. Such knowledge may ultimately permit the prevention and treatment of mental illness. Gene-targeting allows the analysis of specific genetic alterations in the context of the whole organism. The ability to add, delete or modify genes is particularly useful in the analysis of complex organ systems such as the brain, where half of all genes are thought to be uniquely expressed.
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41c The lab focuses on the adrenergic nervous system in which norepinephrine (NE) and epinephrine are the classic neurotransmitters. By genetically eliminating the biosynthetic enzyme for NE, dopamine beta-hydroxylase (DBH), mutant mice (Dbh-/-) that completely lack NE and epinephrine were created. These mice are conditional mutants in that NE can be restored to the adrenergic terminals by supplying a synthetic amino acid precursor of NE, L-DOPS. The lab is pursuing several fundamental observations that resulted from the creation of these mutant mice. These include the roles of NE in learning and memory, as well as the neuronal physiology and signaling that underlie these effects. They also include the role of NE in the effects of stress. For each of these, potentially important interactions with other transmitters and hormones is also being explored. Finally, Dr. Thomas is pursuing several novel genetic approaches for producing complementary models to the Dbh-/- mice toward a more complete understanding of CNS adrenergic function.
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Description of Research Expertise
22 RESEARCH INTEREST54 The roles of neurotransmission in development, neurophysiology and behavior
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1b RESEARCH TECHNIQUES
66 Mouse molecular genetics, electrophysiology, behavioral studies, molecular expression analysis
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18 RESEARCH SUMMARY
25b Broadly, the lab studies the development and physiology of the mammalian brain. One goal is to define the systems that contribute to specific behaviors, and to understand the mechanisms that underlie these behaviors. Such knowledge may ultimately permit the prevention and treatment of mental illness. Gene-targeting allows the analysis of specific genetic alterations in the context of the whole organism. The ability to add, delete or modify genes is particularly useful in the analysis of complex organ systems such as the brain, where half of all genes are thought to be uniquely expressed.
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41c The lab focuses on the adrenergic nervous system in which norepinephrine (NE) and epinephrine are the classic neurotransmitters. By genetically eliminating the biosynthetic enzyme for NE, dopamine beta-hydroxylase (DBH), mutant mice (Dbh-/-) that completely lack NE and epinephrine were created. These mice are conditional mutants in that NE can be restored to the adrenergic terminals by supplying a synthetic amino acid precursor of NE, L-DOPS. The lab is pursuing several fundamental observations that resulted from the creation of these mutant mice. These include the roles of NE in learning and memory, as well as the neuronal physiology and signaling that underlie these effects. They also include the role of NE in the effects of stress. For each of these, potentially important interactions with other transmitters and hormones is also being explored. Finally, Dr. Thomas is pursuing several novel genetic approaches for producing complementary models to the Dbh-/- mice toward a more complete understanding of CNS adrenergic function.
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108 Zhang L, Ouyang M, Ganellin CR and Thomas, SA: The slow afterhyperpolarization: a target of beta1-adrenergic signaling in hippocampus-dependent memory retrieval. J Neurosci 33: 5006-16, 2013.
fd Ouyang, Y., Young, M.B., Lestini, M.M., Schutsky, K. and Thomas, S.A.: Redundant catecholamine signaling consolidates fear memory via phospholipase C. J Neurosci 32: 1932-41, 2012.
126 Schutsky, K., Ouyang, M., Castelino, C. B., Zhang, L. and Thomas, S. A.: Stress and glucocorticoids impair memory retrieval via β2-adrenergic, Gi/o-coupled suppression of cAMP signaling. J Neurosci 31: 14172-14181, 2011.
107 Schutsky, K., Ouyang, M. and Thomas, S. A.: Xamoterol impairs hippocampus-dependent emotional memory retrieval via Gi/o-coupled β2-adrenergic signaling. Learning & Memory 18: 598-604, 2011.
132 Murchison, C. F., Schutsky, K., Jin, S.-H. and Thomas, S. A.: Norepinephrine and β1-adrenergic signaling facilitate activation of hippocampal CA1 pyramidal neurons during contextual memory retrieval. Neuroscience 181: 109-116, 2011.
e5 Ouyang M, Zhang L, Zhu JJ, Schwede F, Thomas SA: Epac is required for hippocampus-dependent memory retrieval. Proc Natl Acad Sci USA 105: 11993-11997, 2008.
e0 Ouyang M and Thomas SA: A requirement for memory retrieval during and after long-term extinction learning. Proc Natl Acad Sci USA 102: 9347-9352, 2005.
d8 Murchison CF, Zhang X-Y, Zhang W-P, Ouyang M, Lee A, Thomas S: A distinct role for norepinephrine in memory retrieval. Cell 117: 131-143, 2004.
136 Cryan JF, O’Leary OF, Jin S-H, Friedland JC, Ouyang M, Hirsch BR, Page ME, Dalvi A, Lucki, I Thomas SA: Norepinephrine-deficient mice lack responses to antidepressant drugs, including SSRIs. Proc Natl Acad Sci USA 101: 8186-8191, 2004.
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Selected Publications
e3 Young, MB and Thomas, SA: M1-muscarinic Receptors Promote Fear Memory Consolidation via Phospholipase C and the M-current. J Neurosci 34: 1570-1578, 2014.108 Zhang L, Ouyang M, Ganellin CR and Thomas, SA: The slow afterhyperpolarization: a target of beta1-adrenergic signaling in hippocampus-dependent memory retrieval. J Neurosci 33: 5006-16, 2013.
fd Ouyang, Y., Young, M.B., Lestini, M.M., Schutsky, K. and Thomas, S.A.: Redundant catecholamine signaling consolidates fear memory via phospholipase C. J Neurosci 32: 1932-41, 2012.
126 Schutsky, K., Ouyang, M., Castelino, C. B., Zhang, L. and Thomas, S. A.: Stress and glucocorticoids impair memory retrieval via β2-adrenergic, Gi/o-coupled suppression of cAMP signaling. J Neurosci 31: 14172-14181, 2011.
107 Schutsky, K., Ouyang, M. and Thomas, S. A.: Xamoterol impairs hippocampus-dependent emotional memory retrieval via Gi/o-coupled β2-adrenergic signaling. Learning & Memory 18: 598-604, 2011.
132 Murchison, C. F., Schutsky, K., Jin, S.-H. and Thomas, S. A.: Norepinephrine and β1-adrenergic signaling facilitate activation of hippocampal CA1 pyramidal neurons during contextual memory retrieval. Neuroscience 181: 109-116, 2011.
e5 Ouyang M, Zhang L, Zhu JJ, Schwede F, Thomas SA: Epac is required for hippocampus-dependent memory retrieval. Proc Natl Acad Sci USA 105: 11993-11997, 2008.
e0 Ouyang M and Thomas SA: A requirement for memory retrieval during and after long-term extinction learning. Proc Natl Acad Sci USA 102: 9347-9352, 2005.
d8 Murchison CF, Zhang X-Y, Zhang W-P, Ouyang M, Lee A, Thomas S: A distinct role for norepinephrine in memory retrieval. Cell 117: 131-143, 2004.
136 Cryan JF, O’Leary OF, Jin S-H, Friedland JC, Ouyang M, Hirsch BR, Page ME, Dalvi A, Lucki, I Thomas SA: Norepinephrine-deficient mice lack responses to antidepressant drugs, including SSRIs. Proc Natl Acad Sci USA 101: 8186-8191, 2004.
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