Jeffrey Conn Research Group

Doug Sheffler , Ph.D.
Post-Doctoral Fellow

Pharmacology B.S. Biology Saint Vincent College 1999
Ph.D. Biochemistry Case Western Reserve University 2006

Phone: 615-322-6730
Email: doug.sheffler@vanderbilt.edu
Fax: 615-343-3088
Location: 1215 Light Hall

Mailing Address:
Department of Pharmacology
Vanderbilt University School of Medicine
2300 Garland Avenue
Nashville, TN 37232-6600

Curriculum Vita

Douglas James Sheffler, Ph.D., is a post-doctoral research fellow who joined the Conn laboratory in November 2005. Doug obtained his doctoral training in the laboratory of Bryan L. Roth, M.D., Ph.D. at Case Western Reserve University in Cleveland, Ohio. His graduate studies focused on the regulation of 5-hydroxytryptamine 2A (5-HT 2A) receptor signaling via a novel interaction between the third intracellular (i3) loop of the 5-HT 2A receptor and a member of the mitogen-activated protein kinase family, p90 Ribosomal S6 Kinase 2 (RSK2). Doug’s interests are in the complex regulation of G-protein coupled receptors (GPCRs) - GPCR signal transduction, ligand binding, receptor desensitization, and the processes of GPCR internalization and down-regulation. In addition, he has also has a specific interest in both the pharmacology of GPCRs, in general mechanisms of signal transduction, and in the pathogenesis of schizophrenia.

Doug continues to pursue his interest in GPCR signal transduction in the Conn laboratory, working on a number of projects related to the metabotropic glutamate receptors (mGluRs). The mGluRs are family III GPCRs, containing a large extracellular N-terminal domain where their endogenous ligand, glutamate, binds. Over the years, a number of compounds have been discovered that can bind to sites that are distinct from the glutamate (orthosteric) binding site. One class of these compounds is referred to as allosteric potentiators. Allosteric potentiators both bind to a site separate from glutamate (allosteric site) and can potentiate glutamate signaling. Signaling potentiation can occur in a number of ways including increasing the maximal signal elicited by glutamate and/or altering the potency of glutamate or other orthosteric ligands. Doug is closely examining the effects of a number of mGluR1a-selective allosteric potentiators on the signaling of the mGluR1a receptor to a variety of signaling pathways including cAMP accumulation, calcium mobilization, and activation of the ERK1/2 mitogen-activated protein kinase cascade. Although many of these compounds were initially discovered to potentiate calcium signaling, the effects of these compounds on other signal transduction cascades are largely unknown. Elucidation of the full-range of action of these compounds may provide exciting new tools to selectively activate a sub-set of signal transduction cascades.