Colleen Niswender, Ph.D.
Associate Professor
B.S. University of Toledo, 1991 Pharmacy
Ph.D. Vanderbilt University, 1996 Pharmacology
Biosketch and Research Interests
Colleen is currently a Research Associate Professor within the Conn group. She obtained her Ph.D. in 1996 in the lab of Dr. Ronald Emeson at Vanderbilt. During her graduate career Colleen studied the regulation of RNA editing in the mammalian central nervous system and characterized molecular determinants regulating RNA editing events within the AMPA subtype glutamate receptor, GluR2, and the G protein-coupled 5HT2C serotonin receptor. She then pursued postdoctoral studies with Dr. Stan McKnight at the University of Washington, focusing on the study of Protein Kinase A signal transduction using recombinant mouse lines and genetically engineering mutations within the PKA enzyme.
Colleen joined the Conn lab in 2004 and serves as the Director of Molecular Pharmacology for the Vanderbilt Program in Drug Discovery. She has focused on the development of assays to aid in screening programs to search for ligands specific for G protein-coupled receptors (GPCRs) of the muscarinic and metabotropic glutamate receptor families. In conjunction with Vanderbilt’s High Throughput Screening Facility, Colleen and others within the Molecular Pharmacology group identify and characterize compounds that act as allosteric modulations of the various muscarinic receptors and mGluRs. It is hoped that these compounds will eventually provide starting points for clinically relevant drugs providing therapeutic benefit for neurological disorders and psychiatric disorders.
Selected Publications
*Rueter SM, *Burns CM, Coode SA, Mookherje P, Emeson RB. Glutamate receptor RNA editing in vitro by enzymatic conversion of adenosine to inosine. Science 1995;267:1491-1494.
Burns CM, Chu H, Rueter SM, Hutchinson LK, Canton H, Sanders-Bush E, Emeson RB. Regulation of serotonin-2C receptor G-protein coupling by RNA editing. Nature 1997;387:303-308.
Niswender CM, Copeland SC, Emeson RB, Sanders-Bush E. RNA editing of the human serotonin 5-hydroxytryptamine 2C receptor silences constitutive activity. J Biol Chem 1999;274(14):9472-9478.
Niswender CM, Herrick-Davis K, Dilley GE, Meltzer HY, Overholser JC, Stockmeier CA, Emeson RB, Sanders-Bush E. RNA editing of the serotonin 2C receptor: alterations in suicide and implications for serotonergic pharmacotherapy. Neuropsychopharm 2001;24(5):478-491.
Niswender CM, Willis BS, Wallen A, Sweet I, Jetton T, Thompson BR, Wu C, Lange AJ, McKnight GS. Hepatocyte-specific activation of a Protein Kinase A holoenzyme with enhanced sensitivity to cAMP disrupts glucose homeostasis. Genesis, 2005; 43(3):109-119.
Niswender CM, Myers KA, Kim, C, Ayala JE, Conn PJ, Weaver CD. Development of a novel and direct assay for high throughput screening of Gi/o-linked G protein coupled receptors using thallium flux through GIRK channels. Mol Pharmacol, 2008, 73(4):1213-1224.
Shirey JK, Xiang Z, Orton D, Brady AE, Myers KA, Williams R, Rodriguez AL, Weaver CD, Niswender CM, Conn PJ. Development and use of allosteric potentiators to examine the role of M4 mAChR in modulating hippocampal neurotransmission. Nat Chem Biol 2008, 4(1):42-50.
Niswender CM, Johnson KA, Weaver CD, Jones CK, Xiang Z, Luo Q, Rodriguez AL, Marlo JE, de Paulis T, Thompson AD, Days EL, Nalywajko T, Austin CA, Williams MB, Ayala JE, Williams R, Lindsley SW, Conn PJ. Discovery, characterization, and antiparkinsonian effects of novel positive allosteric modulators of metabotropic glutamate receptor 4. Mol Pharmacol, 2008, 74(5):1345-1358. PMCID:PMC2574552
Marlo JE*, Niswender CM*, Days EL, Bridges TM, Xiang, Z, Rodriguez AL, Shirey JK, Brady AE, Nalywajko T, Luo Q, Austin CA, Williams MB, Kim K, Williams R, Orton D, Brown HA, Lindsley CW, Conn PJ. Discovery and chacterization of novel allosteric potentiators of M1 muscarinic receptors reveals multiple modes of activity. Mol Pharmacol, 2008, 75(3):577-588. PMCID: PMC2684909
Bridges TM, Marlo JE, Niswender CM, Jones CK, Jadhav SB, Gentry PR, Plumley HC, Weaver CD, Conn PJ, Lindsley CW. Discovery of the first highly M5-preferring muscarinic acetylcholine receptor ligand, an M5 positive allosteric modulator derived from a series of 5-trifluormethoxy N-benzyl isatins. J Med Chem, 2009 52(11):3445-3448. PMCID: In process
Engers DW, Niswender CM, Weaver CD, Jadhav S, Menon UN, Zamorano R, Conn PJ, Lindsley CW, Hopkins CR. Synthesis and evaluation of a series of heterobiarylamids that are centrally penetrant metabotropic glutamate receptor 4 (mGluR4) positive allosteric modulators (PAMs). J Med Chem, 2009, 52(14):4115-8. PMCID: PMC2765192
Hopkins CR, Lindsley CW, Niswender CM. mGluR4 positive allosteric modulation as potential treatment of Parkinson’s disease. Future Med Chem, 2009, 1(3): 501-513. PMCID: PMC2790174
Sheffler DJ, Williams R, Bridges TM, Xiang Z, Kane AS, Byun NE, Jadhav S, Mock MM, Zheng F, Lewis LM, Jones CK, Niswender CM, Weaver CD, Lindsley CW, Conn PJ. A novel selective muscairnic acetylcholine receptor subtype 1 antagonist reduced seizures without impairing hippocampus-dependent learning. Mol Pharmacol, 2009, 76(2):356-68. PMCID: PMC2713127
Niswender CM, Johnson KA, Ayala JE, Luo Q, Williams R, Saleh S, Orton D, Weaver CD, Conn PJ. Context-dependent pharmacology induced by negative allosteric modulators of metabotropic glutamate receptor 7. Mol Pharmacol, 2010, 77(3):459-468. PMCID: PMC2835423
LeBois EP, Bridges TM, Lewis LM, Dawson ES, Kane AS, Xiang Z, Jadhav SB, Yin H, Kennedy JP, Meiler J, Niswender CM, Jones CK, Conn PJ, Weaver CD, Lindsley CW. Discovery and characterization of novel subtype-selective allosteric agonists for the investigation of M1 receptor function in the central nervous system. ACS Chemical Neurosci, 2010, 1(2):104-121. PMCID: in process
*Denotes co-first or co-corresponding authors
