David R. Manning, Ph.D.

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Professor of Pharmacology
Department: Pharmacology
Graduate Group Affiliations

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

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. in press 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.

Page ME, Cryan JF, Sullivan A, Dalvi A, Saucy B, Manning DR, Lucki I: Behavioral and neurochemical effects of 5-(4-[4-(5-Cyano-3-indolyl)-butyl)-butyl]-1-piperazinyl)-benzofuran-2-carboxamide (EMD 68843): A combined selective inhibitor of serotonin reuptake and 5-hydroxytryptamine(1A) receptor partial agonist. JPET 302: 1220-1227, 2002.

Yang J, Wu J, Jiang H, Mortensen R, Austin S, Manning DR, Woulfe D, Brass LF: Signaling through Gi family members in platelets. Redundancy and specificity in the regulation of adenylyl cyclase and other effectors. J Biol Chem 277: 46035-46042, 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: 07/15/2011
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