Michael Keiser, PhD

Title(s)Associate Professor, Institute for Neurodegenerative Diseases
SchoolSchool of Medicine
Address675 Nelson Rising Lane, #416A
San Francisco CA 94158
ORCID ORCID Icon0000-0002-1240-2192 Additional info
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    Other Positions
    Title(s)UCSF Weill Institute for Neurosciences

    Collapse Biography 
    Collapse Education and Training
    University of California, San Francisco, CA2020Diversity, Equity, and Inclusion Champion Training
    Collapse Awards and Honors
    Chan Zuckerberg Initiative2018Ben Barres Early Career Acceleration Award
    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 In The News

    Collapse Research 
    Collapse Research Activities and Funding
    Relating GPCRs by biased ligands for enhanced therapeutic efficacy
    NIH R43MH099712Jan 18, 2013 - Mar 31, 2015
    Role: Principal Investigator
    Calculating target bias in small molecules for library design
    NIH R43GM097912Sep 15, 2011 - Aug 31, 2013
    Role: Principal Investigator
    A platform to predict side-effect targets for drugs
    NIH R44GM093456Jun 1, 2010 - Jul 31, 2016
    Role: Co-Principal Investigator
    Drug Repurposing using Pharmacological Networks
    NIH R43GM093456Jun 1, 2010 - May 31, 2012
    Role: Principal Investigator

    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. to make corrections and additions.
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    1. Toward a generalizable machine learning workflow for neurodegenerative disease staging with focus on neurofibrillary tangles. Acta Neuropathol Commun. 2023 Dec 18; 11(1):202. Vizcarra JC, Pearce TM, Dugger BN, Keiser MJ, Gearing M, Crary JF, Kiely EJ, Morris M, White B, Glass JD, Farrell K, Gutman DA. PMID: 38110981; PMCID: PMC10726581.
      View in: PubMed   Mentions:    Fields:    
    2. ChromaFactor: deconvolution of single-molecule chromatin organization with non-negative matrix factorization. bioRxiv. 2023 Nov 22. Gunsalus LM, Keiser MJ, Pollard KS. PMID: 38045231; PMCID: PMC10690235.
      View in: PubMed   Mentions:
    3. In silico discovery of repetitive elements as key sequence determinants of 3D genome folding. Cell Genom. 2023 Oct 11; 3(10):100410. Gunsalus LM, Keiser MJ, Pollard KS. PMID: 37868032; PMCID: PMC10589630.
      View in: PubMed   Mentions: 2  
    4. Learning chemical sensitivity reveals mechanisms of cellular response. bioRxiv. 2023 Aug 28. Connell W, Garcia K, Goodarzi H, Keiser MJ. PMID: 37693536; PMCID: PMC10491110.
      View in: PubMed   Mentions:
    5. Learning fast and fine-grained detection of amyloid neuropathologies from coarse-grained expert labels. Commun Biol. 2023 06 24; 6(1):668. Wong DR, Magaki SD, Vinters HV, Yong WH, Monuki ES, Williams CK, Martini AC, DeCarli C, Khacherian C, Graff JP, Dugger BN, Keiser MJ. PMID: 37355729; PMCID: PMC10290693.
      View in: PubMed   Mentions: Translation:Humans
    6. The scalable precision medicine open knowledge engine (SPOKE): a massive knowledge graph of biomedical information. Bioinformatics. 2023 02 03; 39(2). Morris JH, Soman K, Akbas RE, Zhou X, Smith B, Meng EC, Huang CC, Cerono G, Schenk G, Rizk-Jackson A, Harroud A, Sanders L, Costes SV, Bharat K, Chakraborty A, Pico AR, Mardirossian T, Keiser M, Tang A, Hardi J, Shi Y, Musen M, Israni S, Huang S, Rose PW, Nelson CA, Baranzini SE. PMID: 36759942; PMCID: PMC9940622.
      View in: PubMed   Mentions: 12     Fields:    
    7. Learning fast and fine-grained detection of amyloid neuropathologies from coarse-grained expert labels. bioRxiv. 2023 Jan 17. Wong DR, Magaki SD, Vinters HV, Yong WH, Monuki ES, Williams CK, Martini AC, DeCarli C, Khacherian C, Graff JP, Dugger BN, Keiser MJ. PMID: 36711704; PMCID: PMC9882138.
      View in: PubMed   Mentions:
    8. Prioritizing Virtual Screening with Interpretable Interaction Fingerprints. J Chem Inf Model. 2022 09 26; 62(18):4300-4318. Fassio AV, Shub L, Ponzoni L, McKinley J, O'Meara MJ, Ferreira RS, Keiser MJ, de Melo Minardi RC. PMID: 36102784.
      View in: PubMed   Mentions: 7     Fields:    
    9. Trans-channel fluorescence learning improves high-content screening for Alzheimer's disease therapeutics. Nat Mach Intell. 2022 Jun; 4(6):583-595. Wong DR, Conrad J, Johnson N, Ayers J, Laeremans A, Lee JC, Lee J, Prusiner SB, Bandyopadhyay S, Butte AJ, Paras NA, Keiser MJ. PMID: 36276634; PMCID: PMC9585544.
      View in: PubMed   Mentions: 5  
    10. Deep learning from multiple experts improves identification of amyloid neuropathologies. Acta Neuropathol Commun. 2022 04 28; 10(1):66. Wong DR, Tang Z, Mew NC, Das S, Athey J, McAleese KE, Kofler JK, Flanagan ME, Borys E, White CL, Butte AJ, Dugger BN, Keiser MJ. PMID: 35484610; PMCID: PMC9052651.
      View in: PubMed   Mentions: 8     Fields:    Translation:Humans
    11. A biomedical open knowledge network harnesses the power of AI to understand deep human biology. AI Mag. 2022; 43(1):46-58. Baranzini SE, Börner K, Morris J, Nelson CA, Soman K, Schleimer E, Keiser M, Musen M, Pearce R, Reza T, Smith B, Herr BW, Oskotsky B, Rizk-Jackson A, Rankin KP, Sanders SJ, Bove R, Rose PW, Israni S, Huang S. PMID: 36093122; PMCID: PMC9456356.
      View in: PubMed   Mentions: 2  
    12. Stress testing reveals gaps in clinic readiness of image-based diagnostic artificial intelligence models. NPJ Digit Med. 2021 Jan 21; 4(1):10. Young AT, Fernandez K, Pfau J, Reddy R, Cao NA, von Franque MY, Johal A, Wu BV, Wu RR, Chen JY, Fadadu RP, Vasquez JA, Tam A, Keiser MJ, Wei ML. PMID: 33479460; PMCID: PMC7820258.
      View in: PubMed   Mentions: 11  
    13. Adding Stochastic Negative Examples into Machine Learning Improves Molecular Bioactivity Prediction. J Chem Inf Model. 2020 12 28; 60(12):5957-5970. Cáceres EL, Mew NC, Keiser MJ. PMID: 33245237.
      View in: PubMed   Mentions: 3     Fields:    
    14. 836 Calibration performance of deep neural networks for image classification declines on real-world, versus curated, test sets. Journal of Investigative Dermatology. 2020 Jul 1; 140(7):s109. Young YA, Pfau PJ, Keiser KM, Wei WM. .
      View in: Publisher Site   Mentions:
    15. 902 Assessing performance of deep neural networks used for image classification by stress testing. Journal of Investigative Dermatology. 2020 Jul 1; 140(7):s119. Young YA, Pfau PJ, Keiser KM, Wei WM. .
      View in: Publisher Site   Mentions:
    16. 383 Assessing deep learning artefact bias using global saliency. Journal of Investigative Dermatology. 2020 Jul 1; 140(7):s49. Pfau PJ, Young YA, Wei WM, Keiser KM. .
      View in: Publisher Site   Mentions:
    17. Learning Molecular Representations for Medicinal Chemistry. J Med Chem. 2020 08 27; 63(16):8705-8722. Chuang KV, Gunsalus LM, Keiser MJ. PMID: 32366098.
      View in: PubMed   Mentions: 37     Fields:    Translation:Cells
    18. Validation of machine learning models to detect amyloid pathologies across institutions. Acta Neuropathol Commun. 2020 04 28; 8(1):59. Vizcarra JC, Gearing M, Keiser MJ, Glass JD, Dugger BN, Gutman DA. PMID: 32345363; PMCID: PMC7189549.
      View in: PubMed   Mentions: 17     Fields:    Translation:Humans
    19. Artificial Intelligence in Dermatology: A Primer. J Invest Dermatol. 2020 08; 140(8):1504-1512. Young AT, Xiong M, Pfau J, Keiser MJ, Wei ML. PMID: 32229141.
      View in: PubMed   Mentions: 37     Fields:    Translation:Humans
    20. Differential methylation and expression of genes in the hypoxia-inducible factor 1 signaling pathway are associated with paclitaxel-induced peripheral neuropathy in breast cancer survivors and with preclinical models of chemotherapy-induced neuropathic pain. Mol Pain. 2020 Jan-Dec; 16:1744806920936502. Kober KM, Lee MC, Olshen A, Conley YP, Sirota M, Keiser M, Hammer MJ, Abrams G, Schumacher M, Levine JD, Miaskowski C. PMID: 32586194; PMCID: PMC7322824.
      View in: PubMed   Mentions: 12     Fields:    Translation:HumansAnimalsCells
    21. Zebrafish behavioural profiling identifies GABA and serotonin receptor ligands related to sedation and paradoxical excitation. Nat Commun. 2019 09 09; 10(1):4078. McCarroll MN, Gendelev L, Kinser R, Taylor J, Bruni G, Myers-Turnbull D, Helsell C, Carbajal A, Rinaldi C, Kang HJ, Gong JH, Sello JK, Tomita S, Peterson RT, Keiser MJ, Kokel D. PMID: 31501447; PMCID: PMC6733874.
      View in: PubMed   Mentions: 13     Fields:    Translation:AnimalsCells
    22. Interpretable classification of Alzheimer's disease pathologies with a convolutional neural network pipeline. Nat Commun. 2019 05 15; 10(1):2173. Tang Z, Chuang KV, DeCarli C, Jin LW, Beckett L, Keiser MJ, Dugger BN. PMID: 31092819; PMCID: PMC6520374.
      View in: PubMed   Mentions: 62     Fields:    Translation:Humans
    23. Comment on "Predicting reaction performance in C-N cross-coupling using machine learning". Science. 2018 11 16; 362(6416). Chuang KV, Keiser MJ. PMID: 30442776.
      View in: PubMed   Mentions: 28     Fields:    
    24. Adversarial Controls for Scientific Machine Learning. ACS Chem Biol. 2018 10 19; 13(10):2819-2821. Chuang KV, Keiser MJ. PMID: 30336670.
      View in: PubMed   Mentions: 15     Fields:    
    25. The Psychiatric Cell Map Initiative: A Convergent Systems Biological Approach to Illuminating Key Molecular Pathways in Neuropsychiatric Disorders. Cell. 2018 07 26; 174(3):505-520. 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. PMID: 30053424; PMCID: PMC6247911.
      View in: PubMed   Mentions: 60     Fields:    Translation:Humans
    26. THE USE OF CONVOLUTIONAL NEURAL NETWORKS TO QUANTIFY AMYLOID PLAQUES IN POSTMORTEM HUMAN BRAIN. Alzheimer's & Dementia. 2018 Jul 1; 14(7):p1446. Chuang CK, Tang TZ, Keiser KM, Beckett BL, DeCarli DC, Jin JL, Dugger DB. .
      View in: Publisher Site   Mentions:
    27. Predicted Biological Activity of Purchasable Chemical Space. J Chem Inf Model. 2018 01 22; 58(1):148-164. Irwin JJ, Gaskins G, Sterling T, Mysinger MM, Keiser MJ. PMID: 29193970; PMCID: PMC5780839.
      View in: PubMed   Mentions: 14     Fields:    
    28. Evolutionarily Conserved Roles for Blood-Brain Barrier Xenobiotic Transporters in Endogenous Steroid Partitioning and Behavior. Cell Rep. 2017 Oct 31; 21(5):1304-1316. 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. PMID: 29091768; PMCID: PMC5774027.
      View in: PubMed   Mentions: 27     Fields:    Translation:AnimalsCells
    29. A Simple Representation of Three-Dimensional Molecular Structure. J Med Chem. 2017 09 14; 60(17):7393-7409. Axen SD, Huang XP, Cáceres EL, Gendelev L, Roth BL, Keiser MJ. PMID: 28731335; PMCID: PMC6075869.
      View in: PubMed   Mentions: 23     Fields:    Translation:Cells
    30. Zebrafish behavioral profiling identifies multitarget antipsychotic-like compounds. Nat Chem Biol. 2016 07; 12(7):559-66. 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. PMID: 27239787; PMCID: PMC4912417.
      View in: PubMed   Mentions: 57     Fields:    Translation:AnimalsCells
    31. Polygenic overlap between schizophrenia risk and antipsychotic response: a genomic medicine approach. Lancet Psychiatry. 2016 Apr; 3(4):350-7. 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. PMID: 26915512; PMCID: PMC4982509.
      View in: PubMed   Mentions: 61     Fields:    Translation:Humans
    32. Leveraging Large-scale Behavioral Profiling in Zebrafish to Explore Neuroactive Polypharmacology. ACS Chem Biol. 2016 Apr 15; 11(4):842-9. McCarroll MN, Gendelev L, Keiser MJ, Kokel D. PMID: 26845413; PMCID: PMC5067259.
      View in: PubMed   Mentions: 14     Fields:    Translation:Animals
    33. Prediction and validation of enzyme and transporter off-targets for metformin. J Pharmacokinet Pharmacodyn. 2015 Oct; 42(5):463-75. Yee SW, Lin L, Merski M, Keiser MJ, Gupta A, Zhang Y, Chien HC, Shoichet BK, Giacomini KM. PMID: 26335661; PMCID: PMC4656030.
      View in: PubMed   Mentions: 22     Fields:    Translation:HumansCells
    34. In Silico Prediction of Drug Side Effects. Antitargets and Drug Safety. 2015 Apr 22; 19-44. Keiser KM. .
      View in: Publisher Site   Mentions:
    35. Systems pharmacology augments drug safety surveillance. Clin Pharmacol Ther. 2015 Feb; 97(2):151-8. Lorberbaum T, Nasir M, Keiser MJ, Vilar S, Hripcsak G, Tatonetti NP. PMID: 25670520; PMCID: PMC4325423.
      View in: PubMed   Mentions: 24     Fields:    Translation:Humans
    36. In silico molecular comparisons of C. elegans and mammalian pharmacology identify distinct targets that regulate feeding. PLoS Biol. 2013 Nov; 11(11):e1001712. Lemieux GA, Keiser MJ, Sassano MF, Laggner C, Mayer F, Bainton RJ, Werb Z, Roth BL, Shoichet BK, Ashrafi K. PMID: 24260022; PMCID: PMC3833878.
      View in: PubMed   Mentions: 11     Fields:    Translation:HumansAnimals
    37. Large-scale prediction and testing of drug activity on side-effect targets. Nature. 2012 Jun 10; 486(7403):361-7. Lounkine E, Keiser MJ, Whitebread S, Mikhailov D, Hamon J, Jenkins JL, Lavan P, Weber E, Doak AK, Côté S, Shoichet BK, Urban L. PMID: 22722194; PMCID: PMC3383642.
      View in: PubMed   Mentions: 296     Fields:    Translation:HumansCells
    38. Chapter 4. Designing Multi-Target Drugs. 2012 Jan 1; 50-65. Gregori-Puigjané GE, Keiser KM. .
      View in: Publisher Site   Mentions:
    39. Chemical informatics and target identification in a zebrafish phenotypic screen. Nat Chem Biol. 2011 Dec 18; 8(2):144-6. Laggner C, Kokel D, Setola V, Tolia A, Lin H, Irwin JJ, Keiser MJ, Cheung CY, Minor DL, Roth BL, Peterson RT, Shoichet BK. PMID: 22179068; PMCID: PMC3262069.
      View in: PubMed   Mentions: 52     Fields:    Translation:Animals
    40. The chemical basis of pharmacology. Biochemistry. 2010 Dec 07; 49(48):10267-76. Keiser MJ, Irwin JJ, Shoichet BK. PMID: 21058655; PMCID: PMC2994275.
      View in: PubMed   Mentions: 36     Fields:    Translation:HumansAnimalsCells
    41. The presynaptic component of the serotonergic system is required for clozapine's efficacy. Neuropsychopharmacology. 2011 Feb; 36(3):638-51. 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. PMID: 21048700; PMCID: PMC3055689.
      View in: PubMed   Mentions: 42     Fields:    Translation:AnimalsCells
    42. Complementarity between a docking and a high-throughput screen in discovering new cruzain inhibitors. J Med Chem. 2010 Jul 08; 53(13):4891-905. Ferreira RS, Simeonov A, Jadhav A, Eidam O, Mott BT, Keiser MJ, McKerrow JH, Maloney DJ, Irwin JJ, Shoichet BK. PMID: 20540517; PMCID: PMC2895358.
      View in: PubMed   Mentions: 65     Fields:    Translation:Humans
    43. Prediction and evaluation of protein farnesyltransferase inhibition by commercial drugs. J Med Chem. 2010 Mar 25; 53(6):2464-71. DeGraw AJ, Keiser MJ, Ochocki JD, Shoichet BK, Distefano MD. PMID: 20180535; PMCID: PMC2867455.
      View in: PubMed   Mentions: 16     Fields:    Translation:AnimalsCells
    44. 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. Thomas KL, Ellingrod VL, Bishop JR, Keiser MJ. PMID: 20581797; PMCID: PMC3807824.
      View in: PubMed   Mentions: 2     Fields:    Translation:Humans
    45. Predicting new molecular targets for known drugs. Nature. 2009 Nov 12; 462(7270):175-81. 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. PMID: 19881490; PMCID: PMC2784146.
      View in: PubMed   Mentions: 617     Fields:    Translation:HumansAnimals
    46. A mapping of drug space from the viewpoint of small molecule metabolism. PLoS Comput Biol. 2009 Aug; 5(8):e1000474. Adams JC, Keiser MJ, Basuino L, Chambers HF, Lee DS, Wiest OG, Babbitt PC. PMID: 19701464; PMCID: PMC2727484.
      View in: PubMed   Mentions: 16     Fields:    Translation:HumansAnimalsCells
    47. Quantifying biogenic bias in screening libraries. Nat Chem Biol. 2009 Jul; 5(7):479-83. Hert J, Irwin JJ, Laggner C, Keiser MJ, Shoichet BK. PMID: 19483698; PMCID: PMC2783405.
      View in: PubMed   Mentions: 72     Fields:    Translation:Cells
    48. Off-target networks derived from ligand set similarity. Methods Mol Biol. 2009; 575:195-205. Keiser MJ, Hert J. PMID: 19727616.
      View in: PubMed   Mentions: 5     Fields:    Translation:Cells
    49. ChemInform Abstract: Quantifying the Relationships among Drug Classes. ChemInform. 2008 Jul 15; 39(29). Hert HJ, Keiser KM, Irwin IJ, Oprea OT, Shoichet SB. .
      View in: Publisher Site   Mentions:
    50. Quantifying the relationships among drug classes. J Chem Inf Model. 2008 Apr; 48(4):755-65. Hert J, Keiser MJ, Irwin JJ, Oprea TI, Shoichet BK. PMID: 18335977; PMCID: PMC2722950.
      View in: PubMed   Mentions: 55     Fields:    Translation:Cells
    51. Relating protein pharmacology by ligand chemistry. Nat Biotechnol. 2007 Feb; 25(2):197-206. Keiser MJ, Roth BL, Armbruster BN, Ernsberger P, Irwin JJ, Shoichet BK. PMID: 17287757.
      View in: PubMed   Mentions: 692     Fields:    Translation:Cells
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