Wesley B. Asher, PhD

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Overview

Dr. Wesley B. Asher is an Assistant Professor in the Division of Molecular Therapeutics in the Neuroscience Research Area of the Department of Psychiatry at Columbia University and a Research Scientist at the Research Foundation of Mental Hygiene, Inc. at the New York State Psychiatric Institute.

Dr. Asher earned a BS in chemistry (biochemistry concentration) and biology from Eastern Kentucky University (2007) and completed his PhD in biophysical chemistry at the University of Rochester (2012) with Drs. Kara Bren and Todd Krauss studying the biogenesis and folding of heme-containing proteins. After completing his graduate work, Dr. Asher did postdoctoral training with Dr. Jonathan Javitch at Columbia University using various biophysical techniques to probe G protein-coupled receptor structure and function.

Email: wa2186@cumc.columbia.edu
Office Phone: 646-774-8603

Academic Appointments

  • Assistant Professor of Clinical Neurobiology (in Psychiatry)

Administrative Titles

  • Research Scientist, Research Foundation for Mental Hygiene, Inc., New York State Psychiatric Institute

Credentials & Experience

Education & Training

  • BS, 2007 Chemistry (Biochemistry Concentration), Eastern Kentucky University, KY
  • BS, 2007 Biology, Eastern Kentucky University, KY
  • MS, 2009 Chemistry, University of Rochester, NY
  • PhD, 2012 Biophysical Chemistry, University of Rochester, NY
  • Fellowship: 2015 Columbia University, NY

Honors & Awards

  • 2015, NARSAD Young Investigator Award, Brain and Behavior Research Foundation
  • 2011, Elon Huntington Hooker Graduate Research Fellowship
  • 2010, DeRight Graduate Research Fellowship
  • 2009, GAANN Graduate Research Fellowship
  • 2009, Edward Peck Curtis Teaching Award, University of Rochester
  • 2008, W. D. Walters Teaching Award, University of Rochester
  • 2008, NSF Graduate Research Fellowship Program Honorable Mention

Research

Dr. Asher’s research in the Division of Molecular Therapeutics focuses on investigating the structural and functional mechanisms of G Protein-Coupled Receptors (GPCRs) and their signaling partners at the molecular level. GPCRs are the largest family of transmembrane-protein receptors that include the dopamine, opioid, and metabotropic glutamate receptors that are major targets for the development of therapeutics treating neuropsychiatric disorders. The structural basis of how drug binding and specificity in GPCRs is transduced into signaling protein activation as well as how receptor dimerization influences signaling are still unclear. Dr. Asher uses a variety of biochemical and biophysical approaches, with a primary focus on using single-molecule imaging techniques to understand receptor signaling and dimerization. Investigating individual receptors and their effectors allows for an unprecedented view into GPCR biology not possible with traditional approaches, with the potential for revealing new insights into molecular events that mediate receptor function.

 

Research Interests

  • G Protein-Coupled Receptors: Structure, Function, and Pharmacology
  • Molecular Mechanisms of Therapeutic Action
  • Molecular Neuroscience
  • Neurobiology of Disease
  • Single-Molecule Biophysics of Transmembrane Receptors

Selected Publications

  • Chakraborty S, DiBerto JF, Faouzi A, Bernhard SM, Gutridge AM, Ramsey S, Zhou Y, Provasi D, Nuthikattu N, Jilakara R, Nelson MNF, Asher WB, Eans S, Wilson L, Chintala SM, Filizola M, van Rijn R, Margolis EB, Roth B, McLaughlin J, Che T, Sames D, Javitch JA, Majumdar S. A novel mitragynine analog with low efficacy mu-opioid receptor agonism displays antinociception with attenuated adverse effects. J Med Chem. 2021. accepted. 
  • Perry-Hauser NA, Asher WB, Hauge Pederson M, Javitch JA. (2021) Assays for detecting arrestin interaction with GPCRs. Methods in Cell Biology. In press. Epub 2021 Jul 17.doi: 10.1016/bs.mcb.2021.06.007.
  • Asher WB, Geggier P, Holsey MD, Gilmore GT, Pati AK, Meszaros J, Terry DS,Mathiasen S, Kaliszewski MJ, McCauley MD, Govindaraju A, Zhou Z, Harikumar KG,Jaqaman K, Miller LJ, Smith AW, Blanchard SC, Javitch JA. Single-molecule FRETimaging of GPCR dimers in living cells. Nature Methods. 2021 Apr;18(4):397-405.doi: 10.1038/s41592-021-01081-y. Epub 2021 Mar 8. PMID: 33686301; PMCID:PMC8232828.
  • Hauge Pedersen M, Pham J, Mancebo H, Inoue A, Asher WB, Javitch JA. A novelluminescence-based β-arrestin recruitment assay for unmodified receptors. J BiolChem. 2021 Jan-Jun;296:100503. doi: 10.1016/j.jbc.2021.100503. Epub 2021 Mar 5. PMID: 33684444; PMCID: PMC8027564.
  • Pati AK, El Bakouri O, Jockusch S, Zhou Z, Altman RB, Fitzgerald GA, Asher WB, Terry DS, Borgia A, Holsey MD, Batchelder JE, Abeywickrama C, Huddle B, Rufa D, Javitch JA, Ottosson H, Blanchard SC. Tuning the Baird aromatic triplet-state energy of cyclooctatetraene to maximize the self-healing mechanism in organic fluorophores. Proc Natl Acad Sci U S A. 2020 Sep 29;117(39):24305-24315. doi: 10.1073/pnas.2006517117. Epub 2020 Sep 10. PMID: 32913060; PMCID: PMC7533661.
  • Asher WB, Mathiasen S, Holsey MD, Grinnell SG, Lambert NA, Javitch JA. (2017) Extreme Vetting of Dopamine Receptor Oligomerization. In: Herrick-Davis K, Milligan G, Di Giovanni G. (eds) G-Protein-Coupled Receptor Dimers. The Receptors, vol 33. Humana Press, Cham. https://doi.org/10.1007/978-3-319-60174-8_5.
  • Zheng Q, Jockusch S, Zhou Z, Altman RB, Zhao H, Asher W, Holsey M, Mathiasen S, Geggier P, Javitch JA, Blanchard SC. Electronic tuning of self-healing fluorophores for live-cell and single-molecule imaging. Chem Sci. 2017 Jan 1;8(1):755-762. doi: 10.1039/C6SC02976K. Epub 2016 Sep 7. PMID: 28377799; PMCID: PMC5299821.
  • Zheng Q, Jockusch S, Zhou Z, Altman RB, Zhao H, Asher W, Holsey M, Mathiasen S, Geggier P, Javitch JA, Blanchard SC. Electronic tuning of self-healing fluorophores for live-cell and single-molecule imaging. Chem Sci. 2017 Jan 1;8(1):755-762. doi: 10.1039/C6SC02976K. Epub 2016 Sep 7. PMID: 28377799; PMCID: PMC5299821.
  • Lee AJ*, Asher WB*, Stern HA, Bren KL, Krauss TD. Single-Molecule Analysis of Cytochrome cFolding by Monitoring the Lifetime of an Attached Fluorescent Probe. J Phys Chem Lett. 2013 Aug 15;4(16):2727-2733. doi: 10.1021/jz401259y. PMID: 24116268; PMCID: PMC3791595. *Contributed equally.
  • Asher WB, Bren KL. A heme fusion tag for protein affinity purification and quantification. Protein Sci. 2010 Oct;19(10):1830-9. doi: 10.1002/pro.460. PMID: 20665691; PMCID: PMC2998719.
  • Asher WB, Hoskins SN, Slasor LA, Morris DH, Cook EM, Bautista DL. Two model system of the alpha1A-adrenoceptor docked with selected ligands. J Chem Inf Model. 2007 Sep-Oct;47(5):1906-12. doi: 10.1021/ci700026v. Epub 2007 Aug 23. PMID: 17715910.