Rebecca J. Howard
Assistant Professor of Chemistry
Office: Dana 218
- B.A. 2001, Pomona College
- Ph.D. 2007, University of California, San Francisco
- Postdoctoral Fellow, 2008-2012, The University of Texas at Austin
At Skidmore since 2012
Affiliated Faculty, Skidmore College Neuroscience Program
The Howard research group uses simple model systems—including bacterial proteins, frog cells, and computer simulations—to study how drugs such as alcohol and anesthetics affect electrical signaling in the human brain. Our primary approach is two-electrode voltage clamp electrophysiology in oocytes from African clawed frogs, a straightforward but powerful method to study cellular electrochemical activity. Students in the Howard group have the opportunity to gain expertise in this widely used technique, as well as nucleic acid mutagenesis and puriﬁcation, reagent preparation, electrophysiological measurements and analysis, protein oxidation and reduction, and molecular modeling and dynamics, among other things. Our research applies recent advances in biochemistry, chemical biology, pharmacology, and biophysics to the critical and fascinating subject of drug use and abuse. For example, we recently demonstrated that alcohol (ethanol) enhances the amount of current conducted by certain ion channel proteins. By mutating speciﬁc amino acid residues in these proteins, we are able to increase or decrease their sensitivity to alcohol. Using these data, we are collaborating with computational chemists to simulate the binding of alcohol to the protein. We are now testing the predictions of our binding models, and continuing to probe for additional important drug-protein interactions.
- CH 105 Chemical Principles I
- CH 341 Biochemistry: Macromolecular Structure & Function
- CH 342 Biochemistry: Intermediary Metabolism
- CH 343 Experimental Biochemistry
- CH 377/378 Senior Seminar in Chemistry and Biochemistry
- SSP 100 Under the Influence: Alcohol in Science and Society (Scribner Seminar)
SELECTED PUBLICATIONS (*authors contributed equally to this work)
- Howard RJ, Trudell JR, Harris RA (2014) Seeking structural specificity: direct modulation of pentameric ligand-gated ion channels by alcohols and anesthetics. Pharmacol Rev 66: 396–412.
- Heusser SA, Howard RJ, Borghese CM, Cullins MA, Broemstrup T, Lee US, Lindahl E, Carlsson J, Harris RA (2013) Functional validation of virtual screening for novel agents with general anesthetic action at ligand-gated ion channels. Mol Pharmacol 84: 670-8.
- Broemstrup T, Howard RJ, Trudell JR, Harris RA, Lindahl E (2013) Inhibition versus potentiation of ligand-gated ion channels can be altered by a single mutation that moves ligands between intra- and intersubunit sites. Structure 21: 1307-16.
- Sauguet L*, Howard RJ*, Malherbe L, Lee US, Corringer P-J, Harris RA, Delarue M (2013) Structural basis for potentiation by alcohols and anaesthetics in a ligand-gated ion channel. Nature Commun 4: 1697.
- Spurny R, Billen B, Howard RJ, Brams M, Debaveye S, Price K, Weston D, Strelkov S, Tytgat J, Bertrand S, Bertrand D, Lummis S, Ulens C (2013) Multisite binding of a general anesthetic to the prokaryotic pentameric Erwinia crysanthemiligand-gated ion channel (ELIC). J Biol Chem 288: 8355–64.
- Murail S, Howard RJ, Broemstrup T, Bertaccini EJ, Harris RA, Trudell JR, Lindahl E (2012) Molecular mechanism for the dual alcohol modulation of Cys-loop receptors. PLoS Comput Biol 8: e1002710.
- Johnson WD, Howard RJ, Trudell JR, Harris RA (2012) The TM2 6′ position of GABA(A) receptors mediates alcohol inhibition. J Pharmacol Exp Ther 340: 445–56.
- Howard RJ, Murail S, Ondricek KE, Corringer P-J, Lindahl E, Trudell JR, Harris RA (2011) Structural basis for alcohol modulation of a pentameric ligand-gated ion channel. Proc Natl Acad Sci USA 108: 12149–54.
- Howard RJ, Slesinger PA, Davies DL, Das J, Trudell JR, Harris RA (2011) Alcohol binding sites in distinct brain proteins: the quest for atomic level resolution. Alcohol Clin Exp Res 35: 1561–73.
- Howard RJ, Clark KA, Holton JM, Minor DL (2007) Structural insight into KCNQ (Kv7) channel assembly and channelopathy. Neuron 53: 663–75.
- Walden H, Podgorski MS, Huang DT, Miller DW, Howard RJ, Minor DL, Holton JM, Schulman BA (2003) The structure of the APPBP1-UBA3-NEDD8-ATP complex reveals the basis for selective ubiquitin-like protein activation by an E1. Mol Cell 12: 1427–37.
- Blackwell HE, Sadowsky JD, Howard RJ, Sampson JN, Chao JA, Steinmetz WE, O’Leary DJ, Grubbs RH (2001) Ring-closing metathesis of olefinic peptides: design, synthesis, and structural characterization of macrocyclic helical peptides. J Org Chem 66: 5291–302.
- American Chemical Society
- American Society for Pharmacology and Experimental Therapeutics
- Association for Women in Science
- Biophysical Society
- International Society for Biomedical Research on Alcoholism
- Research Society on Alcoholism
- Society for Neuroscience