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David R. Manning, Ph.D.

Professor of Pharmacology
Academic Coordinator for Graduate Education, Department of Pharmacology, University of Pennsylvania School of Medicine
Department: Pharmacology

Contact information
Department of Pharmacology
114 John Morgan Building
3620 Hamilton Walk
Philadelphia, PA 19104-6084
Office: (215) 898-1775
Fax: (215) 573-7188
Graduate Group Affiliations
Education:
B.A. (Biology)
University of California at San Diego, 1975.
Ph.D. (Physiology/Pharmacology)
University of California at San Diego, 1980.
Permanent link
 
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Description of Research Expertise

The major focus of the laboratory is the process by which the binding of hormones to cell-surface receptors is translated into the regulation of target enzymes and ion channels. The Manning laboratory is specifically interested in pathways of transduction defined by heterotrimeric GTP-binding regulatory proteins (G proteins). Current studies include mapping linkages among receptors and G proteins in intact cells, defining post-translational modifications of G protein subunits that influence targeting and protein-protein interactions, and exploring the roles of novel G proteins. Considerable effort in the laboratory is devoted toward understanding the relevance of G proteins to the actions of the Hedgehog morphogens. We are currently pursuing noncanonical forms of signaling achieved by Hedgehogs using the Gi family of G proteins. We are also interested in the activation of the one or more forms of Gli transcription factors by ligands apart from Hedgehogs, and specifically through receptors that couple to the G12/13 family. Pursuit of these interests have required the development of methods to evaluate the communication of receptors with G proteins, with an emphasis placed on determinants of efficacy. The idea that ligands working through a single receptor can generate different signals (functional selectivity), or that these signals can be generated by a single ligand as function of ligand concentration, represents a common theme of the work.

Selected Publications

Guo, X., N.A. Riobo-Del Galdo, E.J. Kim, G.R. Grant, and D.R. Manning: Overlap in signaling between Smoothened and the alpha subunit of the heterotrimeric G protein G13. PLOS ONE 2018 Notes: https://doi.org/10.1371/journal.pone0197442.

Shen, F, L Cheng, AE Douglas, NA Riobo, and DR Manning: Smoothened is a fully competent activator of the heterotrimeric G protein G(i). Mol Pharmacol 83: 691, 2013.

Polizio, A.H., Chinchilla, P., Chen, X., Kim, S., Manning, D.R., Riobo, N.A.: Heterotrimeric Gi proteins link Hedgehog signaling to activation of Rho small GTPases to promote fibroblast migration. J Biol Chem 286: 19589-19596, 2011.

Douglas, A.E., Heim, J.A., Shen, F., Amada, L.L., Riobo, N.A., Fernandez-Zapico, M.E., Manning, D.R.: The alpha subunit of the G protein G13 regulates the activity of one or more Gli transcription factors independently of Smoothened. J Biol Chem 286: 30714, 2011.

Crouthamel M, Abankwa D, Zhang L, Dilizio C, Manning DR, Hancock JF, Wedegaertner PB: An N-terminal polybasic motif of G{alpha}q is required for signaling and influences membrane nanodomain distribution Mol Pharmacol Page: In Press [Epub ahead of print] July 27 2010.

Zhang L, Brass LF and Manning DR: The Gq and G12 families of heterotrimeric G proteins report functional selectivity. Mol Pharmacol 75: 235-241, 2009.

Riobo NA, Saucy B, Dilizio C, Manning DR: Activation of heterotrimeric G proteins by Smoothened. Proc Natl Acad Sci USA 103: 12607-12612, 2006.

Zhang L, DiLizio C, Kim D, Smyth EM, Manning DR: The G12 family of G proteins as a reporter of thromboxane A2 receptor activity. Molec Pharmacol 69: 1433-1440, 2006.

Windh RT and Manning DR: Analysis of G protein activation in Sf9 and mammalian cells by agonist-promoted [35S]GTP gamma S binding. Methods in Enzymology 344: 3-14, 2002.

Windh RT and Manning DR: Expression of G protein-coupled receptors and G proteins in Sf9 cells: Analysis of coupling by radioligand binding. Methods in Enzymology 343: 417-429, 2002.

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Last updated: 06/14/2018
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