Michael Keiser, PhD

Associate Professor; CZI Ben Barres Investigator; Allen Distinguished Investigator

Michael is a Chan Zuckerberg Initiative Ben Barres Investigator and a Paul G. Allen Distinguished Investigator. Michael joined the UCSF faculty in 2014, in the Dept. of Pharmaceutical Chemistry and the Institute for Neurodegenerative Diseases, with appointments in the Dept. of Bioengineering & Therapeutic Sciences and the Bakar Computational Health Sciences Institute. He is also a member of the Quantitative Biosciences Institute and the Kavli Institute for Fundamental Neuroscience at UCSF.

Before this, he co-founded a startup bringing systems pharmacology methods for drug-target prediction to pharma and the US FDA, where they are in use today. During his bioinformatics Ph.D. at UCSF as a NSF Fellow, Michael developed techniques to relate drugs and proteins from the statistical similarity of their ligands, such as the Similarity Ensemble Approach (SEA). He holds multiple degrees from Stanford, including a BSc. in Computer Science.

Lab papers

1. Retrieval augmented docking using hierarchical navigable small worlds.

   Hall BW, Keiser MJ. chemRxiv. 2024 Apr 24.

2. Metric Ion Classification (MIC)- A deep learning tool for assigning ions and waters in cryo-EM and x-ray crystallography structures.

   Shub L, Liu W, Skiniotis G, Keiser MJ, Robertson MJ. bioRxiv. 2024 Mar 19.

3. Deep phenotypic profiling of neuroactive drugs in larval zebrafish.

   Gendelev L, Taylor J, Myers-Turnbull D, Chen S, McCarroll MN, Arkin MR, Kokel D, Keiser MJ. bioRxiv. 2024 Feb 25.

4. Proximity Graph Networks- Predicting Ligand Affinity with Message Passing Neural Networks.

   Gale-Day ZJ, Shub L, Chuang KV, Keiser MJ. chemRxiv. 2024 Feb 23.

5. Toward a generalizable machine learning workflow for neurodegenerative disease staging with focus on neurofibrillary tangles.

   Vizcarra JC, Pearce TM, Dugger BN, Keiser MJ, Gearing M, Crary JF, Kiely EJ, Morris M, White B, Glass JD, Farrell K, Gutman DA. Acta Neuropathol Commun. 2023 Dec 18.

6. ChromaFactor- deconvolution of single-molecule chromatin organization with non-negative matrix factorization.

   Gunsalus LM, Keiser MJ, Pollard KS. bioRxiv. 2023 Nov 22.

7. Autoregressive fragment-based diffusion for pocket-aware ligand design.

   Ghorbani M, Gendelev L, Beroza P, Keiser MJ. arXiv - NeurIPS GenBio. 2023 Nov 2.

8. In silico discovery of repetitive elements as key sequence determinants of 3D genome folding.

   Gunsalus LM, Keiser MJ, Pollard KS. Cell Genom. 2023 Oct 11.

9. Learning chemical sensitivity reveals mechanisms of cellular response.

   Connell W, Garcia K, Goodarzi H, Keiser MJ. bioRxiv. 2023 Aug 28.

10. Learning fast and fine-grained detection of amyloid neuropathologies from coarse-grained expert labels.

    Wong DR, Magaki SD, Vinters HV, Yong WH, Monuki ES, Williams CK, Martini AC, DeCarli C, Khacherian C, Graff JP, Dugger BN, Keiser MJ. Commun Biol. 2023 Jun 24.

11. A single-cell gene expression language model.

    Connell W, Khan U, Keiser MJ. arXiv - NeurIPS LMRL. 2022 Oct 25.

12. Prioritizing Virtual Screening with Interpretable Interaction Fingerprints.

    Fassio AV, Shub L, Ponzoni L, McKinley J, O’Meara MJ, Ferreira RS, Keiser MJ, de Melo Minardi RC. J Chem Inf Model. 2022 Sep 26.

13. Simultaneous analysis of neuroactive compounds in zebrafish.

    Myers-Turnbull D, Taylor JC, Helsell C, McCarroll MN, Ki CS, Tummino TA, Ravikumar S, Kinser R, Gendelev L, Alexander R, Keiser MJ, Kokel D. bioRxiv. 2022 Jun 15.

14. Trans-channel fluorescence learning improves high-content screening for Alzheimer's disease therapeutics.

    Wong DR, Conrad J, Johnson N, Ayers J, Laeremans A, Lee JC, Lee J, Prusiner SB, Bandyopadhyay S, Butte AJ, Paras NA, Keiser MJ. Nat Mach Intell. 2022 Jun.

15. Deep learning from multiple experts improves identification of amyloid neuropathologies.

    Wong DR, Tang Z, Mew NC, Das S, Athey J, McAleese KE, Kofler JK, Flanagan ME, Borys E, White CL 3rd, Butte AJ, Dugger BN, Keiser MJ. Acta Neuropathol Commun. 2022 Apr 28.

16. Stress testing reveals gaps in clinic readiness of image-based diagnostic artificial intelligence models.

    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. NPJ Digit Med. 2021 Jan 21.

17. Adding Stochastic Negative Examples into Machine Learning Improves Molecular Bioactivity Prediction.

    Caceres EL, Mew NC, Keiser MJ. J Chem Inf Model. 2020 Dec 28.

18. Predicting Cellular Drug Sensitivity using Conditional Modulation of Gene Expression.

    Connell W, Keiser MJ. bioRxiv - NeurIPS LMRL. 2020 Dec 11.

19. Attention-Based Learning on Molecular Ensembles.

    Chuang KV, Keiser MJ. arXiv - NeurIPS ML4Molecules. 2020 Nov 25.

20. Learning Molecular Representations for Medicinal Chemistry.

    Chuang KV, Gunsalus LM, Keiser MJ. J Med Chem. 2020 Aug 27.

21. Artificial Intelligence in Dermatology- A Primer.

    Young AT, Xiong M, Pfau J, Keiser MJ, Wei ML. J Invest Dermatol. 2020 Aug.

22. Robust Semantic Interpretability- Revisiting Concept Activation Vectors.

    Pfau J, Young AT, Wei J, Wei ML, Keiser MJ. arXiv - ICML - WHI. 2020 Jul 17.

23. Validation of machine learning models to detect amyloid pathologies across institutions.

    Vizcarra JC, Gearing M, Keiser MJ, Glass JD, Dugger BN, Gutman DA. Acta Neuropathol Commun. 2020 Apr 28.

24. Global Saliency- Aggregating Saliency Maps to Assess Dataset Artefact Bias.

    Pfau J, Young AT, Wei ML, Keiser MJ. arXiv - NeurIPS ML4H. 2019 Oct 16.

25. Zebrafish behavioural profiling identifies GABA and serotonin receptor ligands related to sedation and paradoxical excitation.

    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. Nat Commun. 2019 Sep 9.

26. Interpretable classification of Alzheimer's disease pathologies with a convolutional neural network pipeline.

    Tang Z, Chuang KV, DeCarli C, Jin LW, Beckett L, Keiser MJ, Dugger BN. Nat Commun. 2019 May 15.

27. Comment on "Predicting reaction performance in C-N cross-coupling using machine learning".

    Chuang KV, Keiser MJ. Science. 2018 Nov 16.

28. Adversarial Controls for Scientific Machine Learning.

    Chuang KV, Keiser MJ. ACS Chem Biol. 2018 Oct 19.

29. The Psychiatric Cell Map Initiative- A Convergent Systems Biological Approach to Illuminating Key Molecular Pathways in Neuropsychiatric Disorders.

    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. Cell. 2018 Jul 26.

30. Predicted Biological Activity of Purchasable Chemical Space.

    Irwin JJ, Gaskins G, Sterling T, Mysinger MM, Keiser MJ. J Chem Inf Model. 2018 Jan 22.

31. Evolutionarily Conserved Roles for Blood-Brain Barrier Xenobiotic Transporters in Endogenous Steroid Partitioning and Behavior.

    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. Cell Rep. 2017 Oct 31.

32. A Simple Representation of Three-Dimensional Molecular Structure.

    Axen SD, Huang XP, Caceres EL, Gendelev L, Roth BL, Keiser MJ. J Med Chem. 2017 Sep 14.

33. Zebrafish behavioral profiling identifies multitarget antipsychotic-like compounds.

    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. Nat Chem Biol. 2016 Jul.

34. Leveraging Large-scale Behavioral Profiling in Zebrafish to Explore Neuroactive Polypharmacology.

    McCarroll MN, Gendelev L, Keiser MJ, Kokel D. ACS Chem Biol. 2016 Apr 15.

35. Polygenic overlap between schizophrenia risk and antipsychotic response- a genomic medicine approach.

    Ruderfer DM, Charney AW, Readhead B, Kidd BA, Kahler AK, Kenny PJ, Keiser MJ, Moran JL, Hultman CM, Scott SA, Sullivan PF, Purcell SM, Dudley JT, Sklar P. Lancet Psychiatry. 2016 Apr.

36. Prediction and validation of enzyme and transporter off-targets for metformin.

    Yee SW, Lin L, Merski M, Keiser MJ, Gupta A, Zhang Y, Chien HC, Shoichet BK, Giacomini KM. J Pharmacokinet Pharmacodyn. 2015 Oct.

37. Systems pharmacology augments drug safety surveillance.

    Lorberbaum T, Nasir M, Keiser MJ, Vilar S, Hripcsak G, Tatonetti NP. Clin Pharmacol Ther. 2015 Feb.

38. In silico molecular comparisons of C. elegans and mammalian pharmacology identify distinct targets that regulate feeding.

    Lemieux GA, Keiser MJ, Sassano MF, Laggner C, Mayer F, Bainton RJ, Werb Z, Roth BL, Shoichet BK, Ashrafi K. PLoS Biol. 2013 Nov.

39. Large-scale prediction and testing of drug activity on side-effect targets.

    Lounkine E, Keiser MJ, Whitebread S, Mikhailov D, Hamon J, Jenkins JL, Lavan P, Weber E, Doak AK, Cote S, Shoichet BK, Urban L. Nature. 2012 Jun 10.

40. Chemical informatics and target identification in a zebrafish phenotypic screen.

    Laggner C, Kokel D, Setola V, Tolia A, Lin H, Irwin JJ, Keiser MJ, Cheung CY, Minor DL Jr, Roth BL, Peterson RT, Shoichet BK. Nat Chem Biol. 2011 Dec 18.

41. The presynaptic component of the serotonergic system is required for clozapine's efficacy.

    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. Neuropsychopharmacology. 2011 Feb.

42. The chemical basis of pharmacology.

    Keiser MJ, Irwin JJ, Shoichet BK. Biochemistry. 2010 Dec 7.

43. Complementarity between a docking and a high-throughput screen in discovering new cruzain inhibitors.

    Ferreira RS, Simeonov A, Jadhav A, Eidam O, Mott BT, Keiser MJ, McKerrow JH, Maloney DJ, Irwin JJ, Shoichet BK. J Med Chem. 2010 Jul 8.

44. Prediction and evaluation of protein farnesyltransferase inhibition by commercial drugs.

    DeGraw AJ, Keiser MJ, Ochocki JD, Shoichet BK, Distefano MD. J Med Chem. 2010 Mar 25.

45. 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.

    Thomas KL, Ellingrod VL, Bishop JR, Keiser MJ. Psychopharmacol Bull. 2010.

46. Predicting new molecular targets for known drugs.

    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. Nature. 2009 Nov 12.

47. A mapping of drug space from the viewpoint of small molecule metabolism.

    Adams JC, Keiser MJ, Basuino L, Chambers HF, Lee DS, Wiest OG, Babbitt PC. PLoS Comput Biol. 2009 Aug.

48. Quantifying biogenic bias in screening libraries.

    Hert J, Irwin JJ, Laggner C, Keiser MJ, Shoichet BK. Nat Chem Biol. 2009 Jul.

49. Off-target networks derived from ligand set similarity.

    Keiser MJ, Hert J. Methods Mol Biol. 2009.

50. Quantifying the relationships among drug classes.

    Hert J, Keiser MJ, Irwin JJ, Oprea TI, Shoichet BK. J Chem Inf Model. 2008 Apr.

51. Relating protein pharmacology by ligand chemistry.

    Keiser MJ, Roth BL, Armbruster BN, Ernsberger P, Irwin JJ, Shoichet BK. Nat Biotechnol. 2007 Feb.