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
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Degrees
- B.S., 2000, University of California, Irvine
- Ph.D., 2006, University of California, San Francisco
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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 SensorsPARP11 inhibition inactivates tumor-infiltrating regulatory T cells and improves the efficacy of immunotherapies
Cell Reports MedicineVisualizing and profiling de novo protein synthesis in Drosophila with cell-type specificity
Methods in cell biologyProximity-dependent mapping of the HCMV US28 interactome identifies RhoGEF signaling as a requirement for efficient viral reactivation
PLoS pathogensRapid cell type-specific nascent proteome labeling in Drosophila
eLifeStructurally distinct PARP7 inhibitors provide new insights into the function of PARP7 in regulating nucleic acid-sensing and IFN-β signaling
Cell Chemical BiologyADP-ribosyltransferases, an update on function and nomenclature
FEBS JournalAllosteric regulation of DNA binding and target residence time drive the cytotoxicity of phthalazinone-based PARP-1 inhibitors
Cell Chemical BiologyMolecular-Scale Dynamics of Long Range Retrograde Brain-Derived Neurotrophic Factor Transport Shaped by Cellular Spatial Context
Frontiers in NeuroscienceSmall Molecules Targeting PTPσ-Trk Interactions Promote Sympathetic Nerve Regeneration
ACS Chemical NeuroscienceStructure-guided design and characterization of a clickable, covalent PARP16 inhibitor
Chemical ScienceThe non-canonical target PARP16 contributes to polypharmacology of the PARP inhibitor talazoparib and its synergy with WEE1 inhibitors
Cell Chemical BiologyTherapeutics That Promote Sympathetic Reinnervation Modulate the Inflammatory Response After Myocardial Infarction
JACC: Basic to Translational ScienceA Sort-Seq Approach to the Development of Single Fluorescent Protein Biosensors
ACS chemical biologyCatching mono- and poly-ADP-ribose readers with synthetic ADP-ribose baits
Molecular CellCharacterization of parp6 function in knockout mice and patients with developmental delay
CellsChemical genetics and proteome-wide site mapping reveal cysteine MARylation by PARP-7 on immune-relevant protein targets
eLifeChemical Proteomics Approach for Profiling the NAD Interactome
Journal of the American Chemical SocietyMitochondrial permeability transition causes mitochondrial reactive oxygen species-and caspase 3-dependent atrophy of single adult mouse skeletal muscle fibers
CellsPASTA
STAR ProtocolsRational design of selective inhibitors of PARP4
RSC Medicinal ChemistryTreatment with a triazole inhibitor of the mitochondrial permeability transition pore fully corrects the pathology of sapje zebrafish lacking dystrophin
Pharmacological ResearchA novel class of cardioprotective small-molecule PTP inhibitors
Pharmacological ResearchCoronavirus infection and PARP expression dysregulate the NAD metabolome
Journal of Biological Chemistry