Michael S. Cohen, Ph.D.

  • Professor of Chemical Physiology and Biochemistry, School of Medicine
  • Neuroscience Graduate Program, School of Medicine
  • Graduate Program in Biomedical Sciences, School of Medicine

Biography

My research program combines chemistry and molecular design to develop novel chemical tools to answer biological questions. Our overall interests are in two main areas: 1. uncovering new roles for nicotinamide adenine dinucleotide (NAD+) regulation in cells and  2. elucidating the function of post-translational modifications (PTMs) by enzymes that use NAD+ as a substrate. A current focus in on the evolutionarily conserved PTM known as ADP-ribosylation. We seek to understanding the impact ADP-ribosylation on cell function as a strategy for therapeutic development. ADP-ribosylation is catalyzed by a family of enzymes known as poly-ADP-ribose polymerases (PARPs, 17 in humans; also referred to as ARTDs), and involves the transfer of ADP-ribose from NAD+ to amino acids in target proteins. Despite being called PARPs, most (12, referred to as mono-PARPs) of the family members catalyze mono-ADP-ribosylation (MARylation) and not poly-ADP-ribosylation (PARylation). Over the last several years we have developed novel chemical tools and approaches, including orthogonal NAD+ analogue-enzyme pairs, selective PARP inhibitors, an NAD+ biosensor, which have provided insights into NAD+ regulation and the function of PARP-mediated MARylation in ways not attainable with conventional methods. 

Education and training

  • Degrees

    • B.S., 2000, University of California, Irvine
    • Ph.D., 2006, University of California, San Francisco
  • Fellowship

    • 2006-11 LSRF Postdoctoral Fellow Weill Cornell Medical College, New York, NY

Honors and awards

  • 2015 Pew Biomedical Scholar
  • 2016 Medical Research Foundation, Richard T. Jones New Investigator Award
  • 2018 ICBS Young Chemical Biologist Award

Publications

Publications

  • A Genetically Encoded Sensor for Real-Time Monitoring of Poly-ADP-Ribosylation Dynamics In Vitro and in Cells

    ACS Sensors
    1. Alix Thomas
    2. Kapil Upadhyaya
    3. Daniel Bejan
    4. Hayden Adoff
    5. Michael Cohen
    6. Carsten Schultz
  • PARP11 inhibition inactivates tumor-infiltrating regulatory T cells and improves the efficacy of immunotherapies

    Cell Reports Medicine
    1. Raghavendra Basavaraja
    2. Hongru Zhang
    3. Ágnes Holczbauer
    4. Zhen Lu
    5. Enrico Radaelli
    6. Charles Antoine Assenmacher
    7. Subin S. George
    8. Vamshidhar C. Nallamala
    9. Daniel P. Beiting
    10. Mirella L. Meyer-Ficca
    11. Ralph G. Meyer
    12. Wei Guo
    13. Yi Fan
    14. Andrew J. Modzelewski
    15. Vladimir S. Spiegelman
    16. Michael S. Cohen
    17. Serge Y. Fuchs
  • Visualizing and profiling de novo protein synthesis in Drosophila with cell-type specificity

    Methods in cell biology
    1. Stefanny Villalobos-Cantor
    2. Ruth M. Barrett
    3. Alec F. Condon
    4. Alicia Arreola-Bustos
    5. Kelsie M. Rodriguez
    6. Michael S. Cohen
    7. Ian Martin
  • Proximity-dependent mapping of the HCMV US28 interactome identifies RhoGEF signaling as a requirement for efficient viral reactivation

    PLoS pathogens
    1. Samuel Medica
    2. Lindsey B. Crawford
    3. Michael Denton
    4. Chan Ki Min
    5. Taylor A. Jones
    6. Timothy Alexander
    7. Christopher J. Parkins
    8. Nicole L. Diggins
    9. Gabriel J. Streblow
    10. Adam T. Mayo
    11. Craig N. Kreklywich
    12. Patricia Smith
    13. Sophia Jeng
    14. Shannon McWeeney
    15. Meaghan H. Hancock
    16. Andrew Yurochko
    17. Michael S. Cohen
    18. Patrizia Caposio
    19. Daniel N. Streblow
  • Rapid cell type-specific nascent proteome labeling in Drosophila

    eLife
    1. Stefanny Villalobos-Cantor
    2. Ruth M. Barrett
    3. Alec F. Condon
    4. Alicia Arreola-Bustos
    5. Kelsie M. Rodriguez
    6. Michael S. Cohen
    7. Ian Martin
  • Structurally distinct PARP7 inhibitors provide new insights into the function of PARP7 in regulating nucleic acid-sensing and IFN-β signaling

    Cell Chemical Biology
    1. Daniel J. Sanderson
    2. Kelsie M. Rodriguez
    3. Daniel S. Bejan
    4. Ninni E. Olafsen
    5. Inga D. Bohn
    6. Ana Kojic
    7. Sunil Sundalam
    8. Ivan R. Siordia
    9. Anna K. Duell
    10. Nancy Deng
    11. Carsten Schultz
    12. Denis M. Grant
    13. Jason Matthews
    14. Michael S. Cohen
  • ADP-ribosyltransferases, an update on function and nomenclature

    FEBS Journal
    1. Bernhard Lüscher
    2. Ivan Ahel
    3. Matthias Altmeyer
    4. Alan Ashworth
    5. Peter Bai
    6. Paul Chang
    7. Michael Cohen
    8. Daniela Corda
    9. Françoise Dantzer
    10. Matthew D. Daugherty
    11. Ted M. Dawson
    12. Valina L. Dawson
    13. Sebastian Deindl
    14. Anthony R. Fehr
    15. Karla L.H. Feijs
    16. Dmitri V. Filippov
    17. Jean Philippe Gagné
    18. Giovanna Grimaldi
    19. Sebastian Guettler
    20. Nicolas C. Hoch
    21. Michael O. Hottiger
    22. Patricia Korn
    23. W. Lee Kraus
    24. Andreas Ladurner
    25. Lari Lehtiö
    26. Anthony K.L. Leung
    27. Christopher J. Lord
    28. Aswin Mangerich
    29. Ivan Matic
    30. Jason Matthews
    31. George Lucian Moldovan
    32. Joel Moss
    33. Gioacchino Natoli
    34. Michael L. Nielsen
    35. Mario Niepel
    36. Friedrich Nolte
    37. John Pascal
    38. Bryce M. Paschal
    39. Krzysztof Pawłowski
    40. Guy G. Poirier
    41. Susan Smith
    42. Gyula Timinszky
    43. Zhao Qi Wang
    44. José Yélamos
    45. Xiaochun Yu
    46. Roko Zaja
    47. Mathias Ziegler
  • Allosteric regulation of DNA binding and target residence time drive the cytotoxicity of phthalazinone-based PARP-1 inhibitors

    Cell Chemical Biology
    1. Moriah R. Arnold
    2. Marie France Langelier
    3. Jessica Gartrell
    4. Ilsa T. Kirby
    5. Daniel J. Sanderson
    6. Daniel S. Bejan
    7. Justina Šileikytė
    8. Sunil K. Sundalam
    9. Shanthi Nagarajan
    10. Parthiban Marimuthu
    11. Anna K. Duell
    12. Anang A. Shelat
    13. John M. Pascal
    14. Michael S. Cohen
  • Molecular-Scale Dynamics of Long Range Retrograde Brain-Derived Neurotrophic Factor Transport Shaped by Cellular Spatial Context

    Frontiers in Neuroscience
    1. Anke Vermehren-Schmaedick
    2. Mark J. Olah
    3. Damien Ramunno-Johnson
    4. Keith A. Lidke
    5. Michael S. Cohen
    6. Tania Q. Vu
  • Small Molecules Targeting PTPσ-Trk Interactions Promote Sympathetic Nerve Regeneration

    ACS Chemical Neuroscience
    1. Matthew R. Blake
    2. Ryan T. Gardner
    3. Haihong Jin
    4. Melanie A. Staffenson
    5. Nicole J. Rueb
    6. Amy M. Barrios
    7. Gregory B. Dudley
    8. Michael S. Cohen
    9. Beth A. Habecker
  • Structure-guided design and characterization of a clickable, covalent PARP16 inhibitor

    Chemical Science
    1. Daniel S. Bejan
    2. Sunil Sundalam
    3. Haihong Jin
    4. Rory K. Morgan
    5. Ilsa T. Kirby
    6. Ivan R. Siordia
    7. Barr Tivon
    8. Nir London
    9. Michael S. Cohen
  • The non-canonical target PARP16 contributes to polypharmacology of the PARP inhibitor talazoparib and its synergy with WEE1 inhibitors

    Cell Chemical Biology
    1. Vinayak Palve
    2. Claire E. Knezevic
    3. Daniel S. Bejan
    4. Yunting Luo
    5. Xueli Li
    6. Silvia Novakova
    7. Eric A. Welsh
    8. Bin Fang
    9. Fumi Kinose
    10. Eric B. Haura
    11. Alvaro N. Monteiro
    12. John M. Koomen
    13. Michael S. Cohen
    14. Harshani R. Lawrence
    15. Uwe Rix
  • Therapeutics That Promote Sympathetic Reinnervation Modulate the Inflammatory Response After Myocardial Infarction

    JACC: Basic to Translational Science
    1. Joseph J. Sepe
    2. Ryan T. Gardner
    3. Matthew R. Blake
    4. Deja M. Brooks
    5. Melanie A. Staffenson
    6. Courtney B. Betts
    7. Sam Sivagnanam
    8. William Larson
    9. Sushil Kumar
    10. Richard G. Bayles
    11. Haihong Jin
    12. Michael S. Cohen
    13. Lisa M. Coussens
    14. Beth A. Habecker
  • A Sort-Seq Approach to the Development of Single Fluorescent Protein Biosensors

    ACS chemical biology
    1. John N. Koberstein
    2. Melissa L. Stewart
    3. Taylor L. Mighell
    4. Chadwick B. Smith
    5. Michael S. Cohen
  • Catching mono- and poly-ADP-ribose readers with synthetic ADP-ribose baits

    Molecular Cell
    1. Michael S. Cohen
  • Characterization of parp6 function in knockout mice and patients with developmental delay

    Cells
    1. Anke Vermehren-Schmaedick
    2. Jeffrey Y. Huang
    3. Madison Levinson
    4. Matthew B. Pomaville
    5. Sarah Reed
    6. Gary A. Bellus
    7. Fred Gilbert
    8. Boris Keren
    9. Delphine Heron
    10. Damien Haye
    11. Christine Janello
    12. Christine Makowski
    13. Katharina Danhauser
    14. Lev M. Fedorov
    15. Tobias B. Haack
    16. Kevin M. Wright
    17. Michael S. Cohen
  • Chemical genetics and proteome-wide site mapping reveal cysteine MARylation by PARP-7 on immune-relevant protein targets

    eLife
    1. Kelsie M. Rodriguez
    2. Sara C. Buch-Larsen
    3. Ilsa T. Kirby
    4. Ivan Rodriguez Siordia
    5. David Hutin
    6. Marit Rasmussen
    7. Denis M. Grant
    8. Larry L. David
    9. Jason Matthews
    10. Michael L. Nielsen
    11. Michael S. Cohen
  • Chemical Proteomics Approach for Profiling the NAD Interactome

    Journal of the American Chemical Society
    1. Justina Šileikytė
    2. Sunil Sundalam
    3. Larry L. David
    4. Michael S. Cohen
  • Mitochondrial permeability transition causes mitochondrial reactive oxygen species-and caspase 3-dependent atrophy of single adult mouse skeletal muscle fibers

    Cells
    1. Sarah K. Skinner
    2. Angelo Solania
    3. Dennis W. Wolan
    4. Michael S. Cohen
    5. Terence E. Ryan
    6. Russell T. Hepple
  • PASTA

    STAR Protocols
    1. Ilsa T. Kirby
    2. Daniel J. Sanderson
    3. Michael S. Cohen
  • Rational design of selective inhibitors of PARP4

    RSC Medicinal Chemistry
    1. Ilsa T. Kirby
    2. Ashley Person
    3. Michael Cohen
  • Treatment with a triazole inhibitor of the mitochondrial permeability transition pore fully corrects the pathology of sapje zebrafish lacking dystrophin

    Pharmacological Research
    1. Anna Stocco
    2. Natalia Smolina
    3. Patrizia Sabatelli
    4. Justina Šileikytė
    5. Edoardo Artusi
    6. Vincent Mouly
    7. Michael Cohen
    8. Michael Forte
    9. Marco Schiavone
    10. Paolo Bernardi
  • A novel class of cardioprotective small-molecule PTP inhibitors

    Pharmacological Research
    1. Salvatore Antonucci
    2. Moises Di Sante
    3. Justina Sileikyte
    4. Jordan Deveraux
    5. Tyler Bauer
    6. Michael J. Bround
    7. Roberta Menabò
    8. Melanie Paillard
    9. Petra Alanova
    10. Michela Carraro
    11. Michel Ovize
    12. Jeffery D. Molkentin
    13. Michael Cohen
    14. Michael A. Forte
    15. Paolo Bernardi
    16. Fabio Di Lisa
    17. Elizabeth Murphy
  • Coronavirus infection and PARP expression dysregulate the NAD metabolome

    Journal of Biological Chemistry
    1. Collin D. Heer
    2. Daniel J. Sanderson
    3. Lynden S. Voth
    4. Yousef M.O. Alhammad
    5. Mark S. Schmidt
    6. Samuel A.J. Trammell
    7. Stanley Perlman
    8. Michael S. Cohen
    9. Anthony R. Fehr
    10. Charles Brenner