Department & Graduate Program Faculty
John A. Allen, PhD
Chemical Biology and Drug Discovery
Chemical Biology and Drug Discovery
Department of Pharmacology and Toxicology
Phone: (409) 772-9621
Fax: (409) 747-7050
BS, Cell Biology, 2002, University of Illinois, Chicago, Illinois
PhD, Physiology and Biophysics, 2008, University of Illinois-School of Medicine
Postdoctoral Fellow, 2008-2011, Pharmacology, University of North Carolina, Chapel Hill, NC
Areas of Research: Neuropharmacology; drug discovery and translational
research for neurological and psychiatric disorders; cell biology,
biochemistry and pharmacology of G protein-coupled receptors.
The main focus of our research is to understand the signal transduction of G protein-coupled receptors (GPCRs) and to identify and advance GPCR-targeted molecules for neurotherapeutic drug discovery. GPCRs are the largest group of signaling proteins in the human genome and an estimated 35% of all marketed drugs act directly to modulate this receptor family. Our primary focus is the neuropharmacology of dopamine, serotonin and novel orphan receptors that control the brain’s striatum and basal ganglia neuronal system. GPCRs within the striatum mediate reward signals underlying the addictive effects of abused drugs as well as dysfunctions observed in movement disorders such as Parkinson's and Huntington's disease. We apply a synergistic approach using cell/molecular, biochemical and systems pharmacology to reveal the mechanisms of GPCR signaling in cells, neurons and in the brain. We also apply large scale screening technologies and medicinal chemistry to discover novel GPCR ligands and test compounds for their therapeutic potential in pre-clinical models of addiction and related neurological diseases.
We use a range of multidisciplinary approaches in our research including identification of GPCR signaling pathways using CRISPR/Cas9 genome editing and transcriptomics, measurement of GPCR signaling in neurons, drug discovery using high throughput screening platforms, microscopy and live cell imaging of GPCR trafficking and behavioral characterization of rodent models with altered components of GPCR signaling machinery.
- Wang P, Felsing DE, Chen H, Stutz SJ, Murphy RE, Cunningham KA, Allen JA* and Zhou J*. Discovery of potent and brain-penetrant GPR52 agonist that suppresses psychostimulant behavior. (2020) Journal of Medicinal Chemistry Nov 25; 63(22):13951-13972. *, co-contributing and co-corresponding authors.
- Felsing DE, Jain MK, and Allen JA. Advances in dopamine D1 receptor ligands for neurotherapeutics. (2019) Current Topics in Medicinal Chemistry July 12; 19(16), pp 1365–1380.
- Wang P, Felsing DE, Chen H, Raval SR, Allen JA*, Zhou J. Synthesis and pharmacological evaluation of non-catechol G protein biased and unbiased dopamine D1 receptor agonists. (2019) ACS Medicinal Chemistry Letters April 5; 10 (5), pp 792–799. *, co-contributing and co-corresponding authors.
- Gray DL, Allen JA, Mente S, O’Connor RE, DeMarco GJ, Efremov I, Tierney P, Volfson D, Davoren J, Guilmette E, Salafia M, Kozak R, and Ehlers MD. Impaired Beta-arrestin recruitment and reduced desensitization by non-catechol agonists of the D1 Dopamine receptor. (2018) Nature Communications 9(1): p.674.
- Huang HS*, Allen JA*, Mabb AM, Mirilyala J, Taylor-Blake B, Sciaky N, Dutton JW, Lee HM, Chen X, Jin J, Bridges AS, Zylka M, Roth BL and Philpot, BD. Topoisomerase inhibitors unsilence the dormant allele of Ube3a in neurons. (2012) Nature Jan 12;485,185–189. (*, equal first author contribution)
- Allen JA and Roth BL. Strategies to discover unexpected targets for drugs active at G protein-coupled receptors. (2011) Annual Review of Pharmacology and Toxicology Feb 10;51:117-44.
- Allen JA, Yost JM, Setola V, Chen X, Sassano MF, Chen M, Peterson S, Yadav PN, Huang XP, Feng B, Jensen NH, Che X, Bai X, Frye SV, Wetsel WC, Caron MG, Javitch JA, Roth BL and Jin J. Discovery of Beta-arrestin biased Dopamine D2 ligands for probing signal transduction pathways essential for antipsychotic efficacy. (2011) Proceedings of the National Academy of Sciences Nov 8;108 (45):18488-93.
- Allen JA, Yadav PN, Setola V, Farrell MS and Roth BL. Schizophrenia risk gene CAV1 is both pro-psychotic and required for atypical antipsychotic drug actions in vivo. (2011) Translational Psychiatry 1, e33; doi:10.1038/tp.2011.35 (epub 16 Aug. 2011)
- Allen JA, Yu JZ, Dave R, Bhatnagar A, Roth BL and Rasenick MM. Caveolin-1 and lipid microdomains regulate Gαs trafficking and attenuate Gαs/adenylyl cyclase signaling. (2009) Molecular Pharmacology Nov;76(5):1082-93.
- Jones KA, Srivastava DP, Allen JA, Strachan RT, Roth BL and Penzes P. Rapid modulation of spine morphology by the 5-HT2A serotonin receptor through kalirin-7 signaling.(2009) Proceedings of the National Academy of Sciences Nov 17;106(46):19575-19580
- Alexander GM, Rogan SC, Abbas AI, Armbruster BN, Pei Y, Allen JA, Nonneman RJ, Moy SS, Nicolelis MA, McNamara JO and Roth BL. Remote control of neuronal activity in transgenic mice expressing evolved G protein-coupled receptors. (2009) Neuron Jul 16;63(1):27-39.