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    Michael Keiser, PhD

    TitleAssistant Professor
    SchoolUCSF School of Medicine
    DepartmentInstitute for Neurodegenerative Diseases
    Address675 Nelson Rising Lane
    San Francisco CA 94158
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      Collapse Biography 
      Collapse Awards and Honors
      Paul G. Allen Family Foundation2015Allen Distinguished Investigator
      Glenn Foundation2014Glenn Award for Research in Biological Mechanisms of Aging
      SF Business Times201440 Under Forty
      UCSF2010Frank M Goyan Award for excellence in physical chemistry
      Wired2009Top 10 Scientific Breakthroughs of 2009
      NSF2006 - 2009Graduate Research Fellow
      US Dept. Education2003 - 2004Foreign Languages and Area Studies Fellow

      Collapse Overview 
      Collapse Overview
      Our lab investigates how small molecules perturb protein target networks to biological and therapeutic effect. In a forward polypharmacology campaign, we are using machine learning and computational methods such as the Similarity Ensemble Approach (SEA) to infer new combinations of targets underlying compound-induced phenotypes in cells and broader model systems. Thinking of each target as a musical note, we predict and test entire chords at a time via chemical-genetic epistasis experiments in models of complex diseases such as neurodegeneration.

      These systems pharmacology inquiries tell us where current understanding of drug action is weak, and because we use human pharmacology to mine for mechanisms, we can apply the therapeutic chords we find directly to the prediction of patient drug responses, adverse drug reactions, and personalized medicine.

      Collapse ORNG Applications 
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      Collapse In The News

      Collapse Bibliographic 
      Collapse Publications
      Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
      List All   |   Timeline
      1. Bruni G, Rennekamp AJ, Velenich A, McCarroll M, Gendelev L, Fertsch E, Taylor J, Lakhani P, Lensen D, Evron T, Lorello PJ, Huang XP, Kolczewski S, Carey G, Caldarone BJ, Prinssen E, Roth BL, Keiser MJ, Peterson RT, Kokel D. Zebrafish behavioral profiling identifies multitarget antipsychotic-like compounds. Nat Chem Biol. 2016 Jul; 12(7):559-66. PMID: 27239787.
        View in: PubMed
      2. Ruderfer DM, Charney AW, Readhead B, Kidd BA, Kähler AK, Kenny PJ, Keiser MJ, Moran JL, Hultman CM, Scott SA, Sullivan PF, Purcell SM, Dudley JT, Sklar P. Polygenic overlap between schizophrenia risk and antipsychotic response: a genomic medicine approach. Lancet Psychiatry. 2016 Apr; 3(4):350-7. PMID: 26915512.
        View in: PubMed
      3. McCarroll MN, Gendelev L, Keiser MJ, Kokel D. Leveraging Large-scale Behavioral Profiling in Zebrafish to Explore Neuroactive Polypharmacology. ACS Chem Biol. 2016 Apr 15; 11(4):842-9. PMID: 26845413.
        View in: PubMed
      4. Yee SW, Lin L, Merski M, Keiser MJ, Gupta A, Zhang Y, Chien HC, Shoichet BK, Giacomini KM. Prediction and validation of enzyme and transporter off-targets for metformin. J Pharmacokinet Pharmacodyn. 2015 Oct; 42(5):463-75. PMID: 26335661; PMCID: PMC4656030.
      5. Lorberbaum T, Nasir M, Keiser M, Vilar S, Hripcsak G, Tatonetti N. Systems pharmacology augments drug safety surveillance. Clin Pharmacol Ther. 2015 Feb; 97(2):151-8. PMID: 25670520; PMCID: PMC4325423 [Available on 02/01/16].
      6. Lemieux GA, Keiser MJ, Sassano MF, Laggner C, Mayer F, Bainton RJ, Werb Z, Roth BL, Shoichet BK, Ashrafi K. In silico molecular comparisons of C. elegans and mammalian pharmacology identify distinct targets that regulate feeding. PLoS Biol. 2013 Nov; 11(11):e1001712. PMID: 24260022; PMCID: PMC3833878.
      7. Lounkine E, Keiser MJ, Whitebread S, Mikhailov D, Hamon J, Jenkins JL, Lavan P, Weber E, Doak AK, Côté S, Shoichet BK, Urban L. Large-scale prediction and testing of drug activity on side-effect targets. Nature. 2012 Jun 21; 486(7403):361-7. PMID: 22722194; PMCID: PMC3383642.
      8. Laggner C, Kokel D, Setola V, Tolia A, Lin H, Irwin JJ, Keiser MJ, Cheung CY, Minor DL, Roth BL, Peterson RT, Shoichet BK. Chemical informatics and target identification in a zebrafish phenotypic screen. Nat Chem Biol. 2012 Feb; 8(2):144-6. PMID: 22179068; PMCID: PMC3262069.
      9. Keiser MJ, Irwin JJ, Shoichet BK. The chemical basis of pharmacology. Biochemistry. 2010 Dec 7; 49(48):10267-76. PMID: 21058655; PMCID: PMC2994275.
      10. Yadav PN, Abbas AI, Farrell MS, Setola V, Sciaky N, Huang XP, Kroeze WK, Crawford LK, Piel DA, Keiser MJ, Irwin JJ, Shoichet BK, Deneris ES, Gingrich J, Beck SG, Roth BL. The presynaptic component of the serotonergic system is required for clozapine's efficacy. Neuropsychopharmacology. 2011 Feb; 36(3):638-51. PMID: 21048700; PMCID: PMC3055689.
      11. Ferreira RS, Simeonov A, Jadhav A, Eidam O, Mott BT, Keiser MJ, McKerrow JH, Maloney DJ, Irwin JJ, Shoichet BK. Complementarity between a docking and a high-throughput screen in discovering new cruzain inhibitors. J Med Chem. 2010 Jul 8; 53(13):4891-905. PMID: 20540517; PMCID: PMC2895358.
      12. DeGraw AJ, Keiser MJ, Ochocki JD, Shoichet BK, Distefano MD. Prediction and evaluation of protein farnesyltransferase inhibition by commercial drugs. J Med Chem. 2010 Mar 25; 53(6):2464-71. PMID: 20180535; PMCID: PMC2867455.
      13. Thomas KL, Ellingrod VL, Bishop JR, Keiser MJ. A pilot study of the pharmacodynamic impact of SSRI drug selection and beta-1 receptor genotype (ADRB1) on cardiac vital signs in depressed patients: a novel pharmacogenetic approach. Psychopharmacol Bull. 2010; 43(1):11-22. PMID: 20581797; PMCID: PMC3807824.
      14. Keiser MJ, Setola V, Irwin JJ, Laggner C, Abbas AI, Hufeisen SJ, Jensen NH, Kuijer MB, Matos RC, Tran TB, Whaley R, Glennon RA, Hert J, Thomas KL, Edwards DD, Shoichet BK, Roth BL. Predicting new molecular targets for known drugs. Nature. 2009 Nov 12; 462(7270):175-81. PMID: 19881490; PMCID: PMC2784146.
      15. Adams JC, Keiser MJ, Basuino L, Chambers HF, Lee DS, Wiest OG, Babbitt PC. A mapping of drug space from the viewpoint of small molecule metabolism. PLoS Comput Biol. 2009 Aug; 5(8):e1000474. PMID: 19701464; PMCID: PMC2727484.
      16. Hert J, Irwin JJ, Laggner C, Keiser MJ, Shoichet BK. Quantifying biogenic bias in screening libraries. Nat Chem Biol. 2009 Jul; 5(7):479-83. PMID: 19483698; PMCID: PMC2783405.
      17. Keiser MJ, Hert J. Off-target networks derived from ligand set similarity. Methods Mol Biol. 2009; 575:195-205. PMID: 19727616.
        View in: PubMed
      18. Hert J, Keiser MJ, Irwin JJ, Oprea TI, Shoichet BK. Quantifying the relationships among drug classes. J Chem Inf Model. 2008 Apr; 48(4):755-65. PMID: 18335977; PMCID: PMC2722950.
      19. Keiser MJ, Roth BL, Armbruster BN, Ernsberger P, Irwin JJ, Shoichet BK. Relating protein pharmacology by ligand chemistry. Nat Biotechnol. 2007 Feb; 25(2):197-206. PMID: 17287757.
        View in: PubMed
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