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
    UCSF Program for Breakthrough Biomedical Research2016New Frontier Research Award
    Paul G. Allen Family Foundation2015Allen Distinguished Investigator
    Glenn Foundation2014Award for Research in Biological Mechanisms of Aging
    SF Business Times201440 Under Forty
    UCSF2010Frank M Goyan Award
    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 Research 
    Collapse Research Activities and Funding
    Relating GPCRs by biased ligands for enhanced therapeutic efficacy
    NIH/NIMH R43MH099712Jan 18, 2013 - Jan 17, 2015
    Role: Principal Investigator
    Calculating target bias in small molecules for library design
    NIH/NIGMS R43GM097912Sep 15, 2011 - Aug 31, 2013
    Role: Principal Investigator
    A platform to predict side-effect targets for drugs
    NIH/NIGMS R44GM093456Jun 1, 2010 - Jul 31, 2015
    Role: Co-Principal Investigator
    Drug Repurposing using Pharmacological Networks
    NIH/NIGMS R43GM093456Jun 1, 2010 - May 31, 2012
    Role: Principal Investigator

    Collapse ORNG Applications 
    Collapse Websites
    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.
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    1. Axen SD, Huang XP, Cáceres EL, Gendelev L, Roth BL, Keiser M. A Simple Representation of Three-Dimensional Molecular Structure. J Med Chem. 2017 Sep 14; 60(17):7393-7409. PMID: 28731335.
      View in: PubMed
    2. 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 M, Peterson RT, Kokel D. Zebrafish behavioral profiling identifies multitarget antipsychotic-like compounds. Nat Chem Biol. 2016 Jul; 12(7):559-66. PMID: 27239787; PMCID: PMC4912417 [Available on 11/30/16].
    3. Ruderfer DM, Charney AW, Readhead B, Kidd BA, Kähler AK, Kenny PJ, Keiser M, 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; PMCID: PMC4982509 [Available on 04/01/17].
    4. McCarroll MN, Gendelev L, Keiser M, 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
    5. Yee SW, Lin L, Merski M, Keiser M, 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.
    6. 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.
    7. Lemieux GA, Keiser M, 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.
    8. Lounkine E, Keiser M, 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 10; 486(7403):361-7. PMID: 22722194; PMCID: PMC3383642.
    9. Laggner C, Kokel D, Setola V, Tolia A, Lin H, Irwin JJ, Keiser M, Cheung CY, Minor DL, Roth BL, Peterson RT, Shoichet BK. Chemical informatics and target identification in a zebrafish phenotypic screen. Nat Chem Biol. 2011 Dec 18; 8(2):144-6. PMID: 22179068; PMCID: PMC3262069.
    10. Keiser M, Irwin JJ, Shoichet BK. The chemical basis of pharmacology. Biochemistry. 2010 Dec 07; 49(48):10267-76. PMID: 21058655; PMCID: PMC2994275.
    11. Yadav PN, Abbas AI, Farrell MS, Setola V, Sciaky N, Huang XP, Kroeze WK, Crawford LK, Piel DA, Keiser M, 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.
    12. Ferreira RS, Simeonov A, Jadhav A, Eidam O, Mott BT, Keiser M, 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 08; 53(13):4891-905. PMID: 20540517; PMCID: PMC2895358.
    13. DeGraw AJ, Keiser M, 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.
    14. Thomas KL, Ellingrod VL, Bishop JR, Keiser M. 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.
    15. Keiser M, 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.
    16. Adams JC, Keiser M, 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.
    17. Hert J, Irwin JJ, Laggner C, Keiser M, Shoichet BK. Quantifying biogenic bias in screening libraries. Nat Chem Biol. 2009 Jul; 5(7):479-83. PMID: 19483698; PMCID: PMC2783405.
    18. Keiser M, Hert J. Off-target networks derived from ligand set similarity. Methods Mol Biol. 2009; 575:195-205. PMID: 19727616.
      View in: PubMed
    19. Hert J, Keiser M, 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.
    20. Keiser M, 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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