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Biography

The main emphasis of the research in the laboratory is to understand the signal transduction of G protein-coupled receptors (GPCRs) and to identify and advance GPCR targeted molecules for therapeutic drug discovery.  GPCRs are the largest group of signaling proteins in the human genome and an estimated 30-40% of all marketed drugs act directly to modulate this receptor family.  Our primary focus is the neuropharmacology of dopamine, serotonin and other GPCRs that control the striatum and basal ganglia neuronal system.  GPCRs within the striatum mediate reward behavior and movement coordination underlying not only addictive effects of abused drugs such as cocaine but also 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 to identify novel GPCR ligands and test compounds for their therapeutic potential in rodent models of addiction and related neuropsychiatric diseases.

In our research we use a range of multidisciplinary approaches involving identification of GPCR signaling pathways using proteomics, measurement of GPCR signaling in neurons, drug discovery using high throughput screening platforms, microscopy and live cell imaging of neuronal GPCR trafficking and behavioral characterization of genetic mouse models with altered components of GPCR signaling machinery.

Background

John Allen recently joined UTMB as an Assistant Professor after spending several years in industry pursuing drug discovery and development.  Dr. Allen received his Ph.D. in  Physiology & Biophysics from the University of Illinois-College of Medicine where he investigated the molecular pharmacology, trafficking and cellular signaling of heterotrimeric G proteins.  He completed post-doctoral training at the University of North Carolina-Chapel Hill with Dr. Bryan Roth’s laboratory where he studied neuronal signaling of 5-HT2A and Dopamine D2 receptors and defined mechanisms of antipsychotic drug action G protein-coupled receptors (GPCRs).  Most recently, John was Principal Scientist and Laboratory Head at Pfizer Neuroscience, where he successfully advanced small molecules into preclinical and clinical drug development programs, including the discovery of signaling biased ligands for Dopamine D1 and D2 receptors.  His recent work at Pfizer defined the mechanisms of action of novel Dopamine D1 receptor agonists which have advanced into clinical trials for the treatment of Parkinson’s disease and schizophrenia.  John’s research on drug discovery and GPCR pharmacology has been extended at UTMB and the Center for Addiction Research, where his laboratory will identify and advance receptor targets and molecules for treating addiction and related neuropsychiatric disorders.  John is the recipient of several awards including a 2011 NARSAD Young Investigator Award, 2009 Young Investigator Award from the American College of Neuropsychopharmacology and a 2015 Rising STAR Award from the University of Texas System.  

Education
  • B.S., 2002, University of Illinois
  • PhD, 2008, University of Illinois
Publications

Allen JA, Coe JW, Davoren JE, Dounay AB, Efremov IV, Gray DL et al. Heteroaromatic compounds and their use as Dopamine D1 ligands. Patent application.  Pfizer, Inc., assignee. World Intellectual Property Organization (WIPO) WO2014072881. (2014) May 15.

Sassano MF, Allen JA, Jin J, Setola V, Wetsel WC, Caron MG, Roth BL.  D2 Functionally Selective Ligands: Novel Therapeutics?  Eiden LE, editor. Boston: Academic Press; (2014). Catecholamine Research in the 21st Century; p.105.

Dichter GS, Damiano CA and Allen JA. Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings. (2012) Journal of Neurodevelopmental Disorders July 19; 4:20

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.(2012) (*, 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 b-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)

Marder SR, Roth BL, Sullivan PF, Scolnick EM, Nestler EJ, Geyer MA, Weinberger DR, Karayiorgou M, Guidotti A, Gingrich J, Akbarian S, Buchanan RW, Lieberman JA, Conn PJ, Haggarty SJ, Law AJ, Campbell B, Krystal JH, Moghaddam B,Sawa A, Caron MG, George SR, Allen JA, and Solis M. Advancing drug discovery for schizophrenia. (2011) Annals of the New York Academy of Sciences Oct;1236 (1):30-43.

Kozikowski AP, Cho SJ, Jensen NH, Allen JA, Svennebring AM, and Roth BL.HTS and rational drug design to generate a class of 5-HT2C-selective ligands for possible use in schizophrenia. (2010) ChemMedChem Aug 2;5(8):1221-5.

Dong S, Allen JA, Farrell MS, and Roth BL. A chemical-genetic approach for precise spatio-temporal control of cellular signaling. (2010) Molecular Biosystems Aug;6(8):1376-80

Strachan R, Allen JA, Sheffler D and Roth BL. p90Ribosomal S6 kinase 2, a novel GPCR kinase, is required for growth factor-mediated attenuation of GPCR signaling. (2010) Biochemistry Mar;49(12):2657-71.

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.

Huang XP, Setola V, Yadav PN, Allen JA, Rogan SC, Hanson SJ, Revankar C, Robers M, Doucette C and Roth BL.Parallel functional activity profiling reveals valvulopathogens are potent 5-HT2B receptor agonists: implications for drug safety assessment. (2009) Molecular Pharmacology Oct;76(4):710-22.

Yan F, Bikbulatov RV, Mocanu V, Dicheva N, Parker CE, Wetsel WC, Mosier PD, Westkaemper RB, Allen JA, Zjawiony JK, and Roth BL. Structure-based design, synthesis, biochemical and pharmacological characterization of novel Salvinorin A analogues as active state probes of theκ-opioid receptor. (2009) Biochemistry Jul28;48(29):6898-908.

Yu, JZ, Dave RH, Allen JA, Sarma T, Rasenick MM. Cytosolic Gαs acts as an intracellular messenger to increase microtubule dynamics and promote neurite outgrowth. (2009) Journal of Biological Chemistry Apr 17;284(16):10462-72.