Marc M. Greenberg

About

Marc Greenberg is the Vernon K. Krieble Professor of Chemistry at Johns Hopkins University, where he has been a faculty member since 2002. His research group focuses on organic and bioorganic chemistry, chemical biology, with particular emphasis on nucleic acids. Greenberg's work involves using organic chemistry, biochemistry, and molecular biology to understand and exploit the reactivity and structure of nucleic acids, aiming to address fundamental questions about nucleic acid chemistry and develop practical tools for biotechnology. He received his Ph.D. at Yale University under Professor Jerome Berson and trained as an American Cancer Society Postdoctoral Fellow at Caltech in Professor Peter Dervan's laboratory. Greenberg holds undergraduate degrees in Chemistry from New York University and in Chemical Engineering from the Cooper Union School of Engineering. He is a Fellow of the American Association for the Advancement of Science and has received several awards, including the Arthur C. Cope Scholar Award from the American Chemical Society in 2016 and an Alfred P. Sloan Foundation fellowship from 1996 to 2000. His research explores the chemical biology of nucleic acids, including understanding how cytotoxic antitumor agents target DNA, and developing tools for biotechnology. His group synthesizes novel molecules and studies their behavior using various physicochemical, biochemical, and biological techniques. Greenberg has also served as the Founding Director of the…

Research topics

• Chemistry
• Biochemistry
• Stereochemistry
• Molecular biology
• Photochemistry

Selected publications

• Identifying Poly(ADP-ribose)-Binding Proteins with Photoaffinity-Based Proteomics

  Journal of the American Chemical Society · 2021-02-17 · 73 citations

  articleOpen accessCorresponding

  Post-translational modification of proteins with poly(ADP-ribose) (PAR) is an important component of the DNA damage response. Four PAR synthesis inhibitors have recently been approved for the treatment of breast, ovarian, and prostate cancers. Despite the clinical significance of PAR, a molecular understanding of its function, including its binding partners, remains incomplete. In this work, we synthesized a PAR photoaffinity probe that captures and isolates endogenous PAR binders. Our method id…

  PublisherOA PDFDOI

• Light-controlled twister ribozyme with single-molecule detection resolves RNA function in time and space

  Proceedings of the National Academy of Sciences · 2020-05-19 · 22 citations

  articleOpen access

  Significance Small ribozymes are widespread in nature and have been engineered for artificial gene control in biotechnology and therapeutic applications. To understand how these simple RNA motifs work, we designed and synthesized a chemically protected “photocaged” nucleotide that blocks ribozyme folding until the block is removed with a short (≤0.03 s) pulse with a blue laser. We combined this tool with a microscope capable of observing single RNA molecules and showed that photocaged ribozymes…

  PublisherOA PDFDOI

• Selective Inhibition of DNA Polymerase β by a Covalent Inhibitor

  Journal of the American Chemical Society · 2021-05-20 · 17 citations

  articleOpen accessSenior authorCorresponding

  DNA polymerase β (Pol β) plays a vital role in DNA repair and has been closely linked to cancer. Selective inhibitors of this enzyme are lacking. Inspired by DNA lesions produced by antitumor agents that inactivate Pol β, we have undertaken the development of covalent small-molecule inhibitors of this enzyme. Using a two-stage process involving chemically synthesized libraries, we identified a potent irreversible inhibitor (14) of Pol β (KI = 1.8 ± 0.45 μM, kinact = (7.0 ± 1.0) × 10–3 s–1). Inhi…

  PublisherOA PDFDOI

• Deoxyguanosine-Linked Bifunctional Inhibitor of SAMHD1 dNTPase Activity and Nucleic Acid Binding

  ACS Chemical Biology · 2023-05-26 · 10 citations

  articleOpen accessCorresponding

  complex indicates that the biphenyl fragment impedes a conformational change in the C-terminal lobe that is required for tetramerization.

  PublisherOA PDFDOI

• 8-Oxo-2′-deoxyguanosine Replication in Mutational Hot Spot Sequences of the <i>p53</i> Gene in Human Cells Is Less Mutagenic than That of the Corresponding Formamidopyrimidine

  Chemical Research in Toxicology · 2023-04-24 · 10 citations

  articleOpen access

  tumor suppressor gene, was replicated in HEK 293T cells. 8-OxodGuo was only a weak block of replication, and the bypass was largely error-free. The mutations (1-5%) were primarily G → T transversions, and the mutation frequency was generally lower than that of the chemically related Fapy·dG. A unique 8-OxodGuo mutation spectrum was observed at each site, as reflected by replication in translesion synthesis (TLS) polymerase- or hPol λ-deficient cells. In codon 248 (CG*G) and 249 (AG*G), where G*…

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01GM063028

  NIH · $5.4M · 2020

• NIH Grant R01CA074954

  NIH · $1.7M · 2008

• NIH Grant R01ES027558

  NIH · $1.7M · 2024

Frequent coauthors

• Kelly M. Kroeger

  Agilent Technologies (United States)

  31 shared

• Brian C. Bales

  GE Global Research (United States)

  27 shared

• Carissa J. Wiederholt

  Johns Hopkins University

  25 shared

• Michael O. Delaney

  Cornell University

  22 shared

• Myron F. Goodman

  University of Southern California

  21 shared

• Murat Saparbaev

  Institut Gustave Roussy

  20 shared

• Jacques Laval

  Université Paris-Saclay

  20 shared

• Jaeseung Kim

  Qurient (South Korea)

  20 shared

Labs

• Marc GreenbergPI

Awards & honors

• Arthur C. Cope Scholar Award from the American Chemical Soci…
• Fellow of the American Association for the Advancement of Sc…
• Alfred P. Sloan Foundation fellow (1996-2000)
• Founding Director of the Chemistry-Biology Interface program…

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