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Michael Keiser, PhD

Title(s)Assistant Professor, Institute for Neurodegenerative Diseases
SchoolSchool of Medicine
Phone415-502-7651
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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. Chuang KV, Keiser MJ. Comment on "Predicting reaction performance in C-N cross-coupling using machine learning". Science. 2018 11 16; 362(6416). PMID: 30442776.
      View in: PubMed
    2. Chuang KV, Keiser MJ. Adversarial Controls for Scientific Machine Learning. ACS Chem Biol. 2018 Oct 19; 13(10):2819-2821. PMID: 30336670.
      View in: PubMed
    3. Willsey AJ, Morris MT, Wang S, Willsey HR, Sun N, Teerikorpi N, Baum TB, Cagney G, Bender KJ, Desai TA, Srivastava D, Davis GW, Doudna J, Chang E, Sohal V, Lowenstein DH, Li H, Agard D, Keiser MJ, Shoichet B, von Zastrow M, Mucke L, Finkbeiner S, Gan L, Sestan N, Ward ME, Huttenhain R, Nowakowski TJ, Bellen HJ, Frank LM, Khokha MK, Lifton RP, Kampmann M, Ideker T, State MW, Krogan NJ. The Psychiatric Cell Map Initiative: A Convergent Systems Biological Approach to Illuminating Key Molecular Pathways in Neuropsychiatric Disorders. Cell. 2018 Jul 26; 174(3):505-520. PMID: 30053424.
      View in: PubMed
    4. Irwin JJ, Gaskins G, Sterling T, Mysinger MM, Keiser MJ. Predicted Biological Activity of Purchasable Chemical Space. J Chem Inf Model. 2018 01 22; 58(1):148-164. PMID: 29193970.
      View in: PubMed
    5. Hindle SJ, Munji RN, Dolghih E, Gaskins G, Orng S, Ishimoto H, Soung A, DeSalvo M, Kitamoto T, Keiser MJ, Jacobson MP, Daneman R, Bainton RJ. Evolutionarily Conserved Roles for Blood-Brain Barrier Xenobiotic Transporters in Endogenous Steroid Partitioning and Behavior. Cell Rep. 2017 Oct 31; 21(5):1304-1316. PMID: 29091768.
      View in: PubMed
    6. Axen SD, Huang XP, Cáceres EL, Gendelev L, Roth BL, Keiser MJ. A Simple Representation of Three-Dimensional Molecular Structure. J Med Chem. 2017 09 14; 60(17):7393-7409. PMID: 28731335.
      View in: PubMed
    7. 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 07; 12(7):559-66. PMID: 27239787; PMCID: PMC4912417 [Available on 11/30/16].
      View in: PubMed, PubMed Central
    8. 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; PMCID: PMC4982509 [Available on 04/01/17].
      View in: PubMed, PubMed Central
    9. 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
    10. 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.
      View in: PubMed, PubMed Central
    11. Lorberbaum T, Nasir M, Keiser MJ, Vilar S, Hripcsak G, Tatonetti NP. Systems pharmacology augments drug safety surveillance. Clin Pharmacol Ther. 2015 Feb; 97(2):151-8. PMID: 25670520; PMCID: PMC4325423.
      View in: PubMed, PubMed Central
    12. 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.
      View in: PubMed, PubMed Central
    13. 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 10; 486(7403):361-7. PMID: 22722194; PMCID: PMC3383642.
      View in: PubMed, PubMed Central
    14. 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. 2011 Dec 18; 8(2):144-6. PMID: 22179068; PMCID: PMC3262069.
      View in: PubMed, PubMed Central
    15. Keiser MJ, Irwin JJ, Shoichet BK. The chemical basis of pharmacology. Biochemistry. 2010 Dec 07; 49(48):10267-76. PMID: 21058655; PMCID: PMC2994275.
      View in: PubMed, PubMed Central
    16. 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.
      View in: PubMed, PubMed Central
    17. 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 08; 53(13):4891-905. PMID: 20540517; PMCID: PMC2895358.
      View in: PubMed, PubMed Central
    18. 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.
      View in: PubMed, PubMed Central
    19. 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.
      View in: PubMed, PubMed Central
    20. 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.
      View in: PubMed, PubMed Central
    21. 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.
      View in: PubMed, PubMed Central
    22. 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.
      View in: PubMed, PubMed Central
    23. Keiser MJ, Hert J. Off-target networks derived from ligand set similarity. Methods Mol Biol. 2009; 575:195-205. PMID: 19727616.
      View in: PubMed
    24. 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.
      View in: PubMed
    25. 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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