Marc Greenberg

Vernon K. Krieble Professor of Chemistry

New Chemistry Building, 313
410-516-8095
mgreenberg@jhu.edu
Group/Lab Website

Marc Greenberg is the Vernon K. Krieble Professor of Chemistry and has been a member of the Johns Hopkins University faculty since 2002. Greenberg received his training as an American Cancer Society Postdoctoral Fellow at Caltech in the laboratory of Professor Peter Dervan and earned his Ph.D. at Yale University under the guidance of Professor Jerome Berson. He has undergraduate degrees in Chemistry and Chemical Engineering from New York University and the Cooper Union School of Engineering, respectively.

Greenberg is a Fellow of the American Association for the Advancement of Science. He was the recipient of an Arthur C. Cope Scholar Award from the American Chemical Society (2016) for his research on nucleic acids, and was an Alfred P. Sloan Foundation fellow (1996-2000). Greenberg was the Founding Director of the Chemistry-Biology Interface program (2005-2013) at Johns Hopkins University.

Nucleic acids play vital roles in health and biotechnology. Our research group uses organic chemistry, biochemistry, and molecular biology to understand and exploit the reactivity and structure of nucleic acids. Our ability to chemically synthesize unnatural molecules and carry out physicochemical and biochemical studies with them enables us to address a variety of biologically important questions at the molecular level.

The investigations carried out in our group are designed to answer fundamental problems concerning nucleic acid chemistry, such as providing chemical insight into how cytotoxic antitumor agents that target DNA kill tumor cells. Practical applications give rise to tools that are useful in biotechnology. To bring these projects to fruition we synthesize novel molecules and study their behavior using a variety of physicochemical, biochemical, and biological techniques.

Recent examples include:

  • Determining how nucleic acids are oxidatively damaged by synthesizing molecules that enable us to independently generate reactive intermediates at defined sites in DNA (eqn. 1) and RNA (eqn. 2).
  • Demonstrating that the histone proteins in nucleosome core particles catalyze DNA cleavage at damaged sites (e.g. C4-AP), and are themselves modified during the process (eqn. 3).
  • Developing novel irreversible inhibitors of DNA repair enzymes (1).
  • Developing radiosensitizing agents that enhance the effects of ionizing radiation on DNA (2).
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Organic Chemistry I – 030.205

Honors Organic Chemistry II – 030.212

Advanced Mechanistic Organic Chemistry I – 030.625

Advanced Mechanistic Organic Chemistry II – 030.626

Organic Chemistry of Nucleic Acids – 030.682

Rapid Histone Catalyzed DNA Lesion Excision and Accompanying Protein Modification in Nucleosomes and Nucleosome Core Particles. Weng, L.; Greenberg, M. M. J. Am. Chem. Soc. 2015, 137, 11022-11031.

Light-Triggered RNA Annealing by an RNA Chaperone. Panja, S.; Paul, R.; Greenberg, M. M.; Woodson, S. A. Angew. Chem. Int. Ed. 2015, 54, 7281-7284.

Rapid RNA Strand Scission Following C2'-Hydrogen Atom Abstraction. Paul, R.; Greenberg, M. M. J. Am. Chem. Soc. 2015, 137, 596-599. (PMC: 4313564)

Probing Interactions Between Histone Tails and Nucleosomal DNA via Product and Kinetic Analysis. Weng, L.; Zhou, C.; Greenberg, M. M. ACS Chem. Biol. 2015, 10, 622-630. "Spotlighted" in Chem. Res. Toxicol. 2015, 28, 3. (PMC: 4336632)

DNA Damage by Histone Radicals in Nucleosome Core Particles. Zhou, C.; Greenberg, M. M. J. Am. Chem. Soc. 2014, 136, 6562-6565. (PMC: 4017609)

Irreversible Inhibition of DNA Polymerase b by Small Molecule Mimics of a DNA Lesion. Arian, D.; Hedayati, M.; Zhou, H.; Bilis, Z.; Chen, K.; DeWeese, T. L.; Greenberg, M. M. J. Am. Chem. Soc. 2014, 136, 3176-3183. (PMC: 4047187)

5.6-Dihydropyrimidine Peroxyl Radical Reactivity in DNA. San Pedro, J. M. N.; Greenberg, M. M. J. Am. Chem. Soc. 2014, 136, 3928-3936. (PMC: 3980663)

DNA Double Strand Cleavage via Interstrand Hydrogen Atom Transfer. Taverna Porro, M. L.; Greenberg, M. M. J. Am. Chem. Soc. 2013, 135, 16368-16371. "Spotlighted" in the J. Am. Chem. Soc. 2013, 135, 16745. Cited by Faculty1000: http://f1000.com/prime/718152314?bd=1&ui=21843. (PMC: 3852885)

Histone Modification via Rapid Cleavage of C4'-Oxidized Abasic Sites in Nucleosome Core Particles. Zhou, C.; Sczepanski, J. T.; Greenberg, M. M. J. Am. Chem. Soc. 2013, 135, 5274-5277. "Spotlighted" in the J. Am. Chem. Soc. 2013, 135, 5933. (PMC: 3638250)

Photochemical Control of RNA Structure by Disrupting p-Stacking. Resendiz, M. J. E.; Schön, A; Freire, E.; Greenberg, M. M. J. Am. Chem. Soc. 2012, 134, 12478-12481. Highlighted by Faculty1000: http://f1000.com/prime/718008044?subscriptioncode=698beb4c-fb8a-4a37-bb37-0f3e5fc23efb#related-articles (PMC: 3416055)

Mechanistic Studies on Histone Catalyzed Cleavage of Apyrimidinic/Apurinic Sites in Nucleosome Core Particles. Zhou, C.; Sczepanski, J. T.; Greenberg, M. M. J. Am. Chem. Soc. 2012, 134, 16734-16741. (PMC: 3477373)

Direct Strand Scission in Double Stranded RNA via a C5-Pyrimidine Radical. Resendiz, M. J. E.; Pottiboyina, V.; Sevilla, M. D.; Greenberg, M. M. J. Am. Chem. Soc. 2012, 134, 3917-3924. (PMC: 3315363)

Histone Catalyzed Cleavage of Nucleosomal DNA Containing 2-Deoxyribonolactone. Zhou, C.; Greenberg, M. M. J. Am. Chem. Soc. 2012, 134, 8090-8093. "Spotlighted" in the J. Am. Chem. Soc. 2012, 134, 9031. (PMC: 3354019)

Product and Mechanistic Analysis of the Reactivity of a C6-Pyrimidine Radical in RNA. Jacobs, A. C.; Resendiz, M. J. E.; Greenberg, M. M. J. Am. Chem. Soc. 2011, 133, 5152-5159. (PMC: 3071645)

Rapid DNA-Protein Cross-linking and Strand Scission by an Abasic Site in a Nucleosome Core Particle. Sczepanski, J. T.; Wong, R. S.; McKnight, J. N.; Bowman, G. D.; Greenberg,, M. M. Proc. Natl. Acad. Sci. USA 2010, 107, 22475-22480. (PMC: 3012510)