Barry Gold is Professor in the Department of Pharmaceutical Sciences at the University of Pittsburgh. He also serves as a co-Director of the University of Pittsburgh Drug Discovery Institute and is a member of the University of Pittsburgh Cancer Institute.
Before moving to Pittsburgh, he was Professor and Associate Director for Basic Research at the University of Nebraska Medical Center’s Eppley Cancer Center. He did his undergraduate, graduate and postgraduate studies in organic chemistry at Hunter College of the City University of New York, the University of Nebraska-Lincoln and the University of Toronto, respectively.
His research interests are related to: (1) The design, synthesis and characterization of heterocyclic C-glycoside molecules that sequence-specifically bind to duplex DNA via triple helix formation. The goal of this work is to gene specifically regulation protein expression and probe transcriptional regulatory sequences; (2) The generation of anticancer drugs that efficiently form DNA lesions that are cytotoxic but not mutagenic in order to minimize secondary cancers; and (3) The development of small molecule inhibitors of specific DNA repair pathways that are involved in tumor resistance to anticancer drugs. He is active in the training of undergraduate, graduate and post-graduate students and has taught courses in medicinal chemistry, biochemistry, biophysical biochemistry, chemical carcinogenesis, nucleic acids and cancer research.
Dr. Gold has published more than 100 peer-reviewed papers and been the lead inventor on three patents. He has maintained continuous NIH funding since 1977. He has been a member of the ACS since 1969. In 2008, he served as the Chair for the 31st National Medicinal Chemistry Symposium that was held in Pittsburgh. Previously, he has been on the executive committee of the ACS Division of Chemical Toxiciology. He has reviewed grants for a number of NIH study sections and for center and program project grants. He is on the editorial advisory boards of Burger’s Medicinal Chemistry and Drug Discovery and Future Medicinal Chemistry.
Dr. Gold has on ongoing involvement with efforts to increase the number of under-represented minorities in science. He has served as a mentor for high school teachers as part of the mentoring program of the Society for the Advancement of Native Americans and Chicanos in Science (SACNAS) and is on the Minority Affairs Committee of the Biophysical Society.
Design and characterization of DNA binding molecules, and recognition of DNA damage.
Burns, N. and Gold, B. The effect of 3-methyladenine-DNA-Glycosylase mediated DNA repair on the induction of toxicity and diabetes by the β-cell toxicant Streptozotocin. Toxicol. Sci. 95, 391-400 (2007).
Ganguly, G., Wang, F., Kaushik, M., Stone, M. P., Marky, L. A. and Gold, B. A study of 7-deaza-2’-deoxyguanosine•2’-deoxycytidine base pairing in DNA. Nucleic Acids Res. 35, 6181-6195 (2007).
Monti, P., Ciribilli, Y., Russo, D., Bisio, A., Perfumo, C., Andreotti, V., Menichini, P., Inga, A., Huang, X., Gold, B. and Fronza, G. REV1 and Polζ influence toxicity and mutagenicity of Me-lex, a sequence selective N3-adenine methylating agent. DNA Repair 7, 431-438 (2008).
Wang, F., Li, F., Ganguly, M., Marky, L. A., Gold, B., Egli, M. and Stone, M. P. A bridging water anchors the tethered 5-(3-aminopropyl)-2’-deoxyuridine amine in the DNA major groove proximate to the N+2 C•G base pair: Implications for formation of interstrand 5’-GNC-3’ cross-links by nitrogen mustards. Biochemistry 47, 7147-7157 (2008).
Wang, R.-W. and Gold, B. A facile synthetic approach to 7-deazaguanine nucleosides via a Boc protection strategy. Org. Lett. 11, 2465-2468 (2009).
Ganguly, M., Wang, R.-W., Marky, L. A. and Gold, B. Introduction of cationic charge into DNA near the major groove edge of a guanine•cytosine base pair: characterization of oligodeoxynucleotides substituted with 7-aminomethyl-7-deaza-2’-deoxyguanosine. J. Am. Chem. Soc. 131, 12068–12069 (2009).
Russo, D., Fronza, G., Ottaggio, L., Monti, P., Inga, A. Iyer, P., Gold, B. and Menichini, P. High frequency of genomic deletions induced by Me-lex, a sequence selective N3-adenine methylating agent, at the Hprt locus in Chinese hamster ovary cells. Mutat. Res., 671, 58-66 (2009).
Monti, P., Traverso, I., Casolari, L., Menichini, P., Inga, A., Ottaggio, L., Russo, D., Iyer, P., Gold, B. and Fronza, G. Mutagenicity of N3-methyadenine: a multi translesion polymerase affair. Mutat. Res. 683, 50-56 (2010).
Ganguly, M., Wang, R.-W., Marky, L. A. and Gold, B. Thermodynamic characterization of DNA with 3-deazaadenine and 3-methyl-3-deazaadenine substitutions. J. Phys. Chem. B 114, 7656-7661 (2010).
Tentori, L. Muzi, A., Dorio, A. S., Scarsella, M., Leonetti, C., Shah, G. M., Xu, W., Camaioni, E., Gold, B., Pellicciari, R., Dantzer, F., Zhang, J. and Graziana, G. Pharmacological inhibition of poly(ADP-ribose) polymerase (PARP) activity in PARP-1 silenced tumor cells increases chemosensitivity to temozolomide and to a N3-adenine selective methylating agent. Curr. Cancer Drug Targ. 10, 368-383 (2010).
Russo, D., Fronza, G. Ottaggio, L., Monti, P. Perfumo, C., Inga, A. Iyer, P., Gold, B. and Menichini, P. Xrcc1 deficiency influences the cytotoxicity and the genomic instability induced by Me-lex, a specific inducer of N3-methyladenine. DNA Repair 9, 728-736 (2010).
Settles, Wang, R.-W., Fronza, G. and Gold, B. Effect of N3-Methyladenine and an isosteric stable analogue on DNA polymerization. J. Nucl. Acids 2010, 426505.
Rubinson, E. H., Gowda, A. S. P., Spratt, T. E., Gold, B. and Eichman, B. F. An unprecedented nucleic acid capture mechanism for excision of DNA damage. Nature 468, 406-411 (2010).
Singh, S. K., Szulik, M. W., Ganguly, M., Khutsishvili, I., Stone, M. P., Marky, L. A. and Gold, B. (2011) Characterization of DNA with an 8-oxoguanine modification. Nucleic Acids Res. 39, 6789-680 .
Monti, P., Broxson, C., Inga, A., Wang, R.-W., Menichini, P., Tornaletti, S., Gold, B. and Fronza, G. (2011) 3-Methyl-3-deazaadenine, a stable isostere of N3-methyl-adenine, is efficiently bypassed by replication in vivo and by transcription in vitro. DNA Repair, 10, 861-868.
Kowal, E., Ganguly, M., Pallan, P., Marky, L. A., Gold, B., Egli, M. Stone, M. P. (2011) Altering the electrostatic potential in the major groove: thermodynamic and structural characterization of 7-deaza-2'-deoxyadenosine•dT base pairing in DNA. J. Phys. Chem. B. 115, 13925-13934.
Ganguly, M., Szulik, M. W., Donahue, P. S., Clancy, K., Michael P. Stone, M. P. and Gold, B. (2012) Thermodynamic signature of DNA damage: characterization of DNA with a 5-hydroxy-2’-deoxycytidine•2’-deoxyguanosine base pair. Biochemistry 51, 2018-2027.
Ganguly, M., Szulik, M. W., Donahue, P. S., Clancy, K., Michael P. Stone, M. P. and Gold, B. Thermodynamic signature of DNA damage: characterization of DNA with a 5-hydroxy-2’-deoxycytidine•2’-deoxyguanosine base pair. Biochemistry 51, 2018-2027 (2012).
Srinivasan, A., and Gold, B. Small molecule inhibitors of DNA damage repair pathways: an approach to overcome tumor resistance to alkylating anticancer drugs. Future Med. Chem. 4, 1093-1111 (2012).
Srinivasan, A. Wang, L., Cline, C. J., Xie, Z., Sobol, R. W., Xie, X-Q. and Gold, B. The identification and characterization of human AP endonuclease-1 inhibitors. Biochemistry 51, 6246-6259 (2012).
Iyer,P., Srinivasan, A., Singh, S. K., Mascara, G. P., Zayitova, S., Sidone, B.,† Fouquerel, E., Svilar, D., Sobol, R. W., Bobola, M. S., Silber, J. R. and Gold, B. Synthesis and Characterization of DNA Minor Groove Binding Alkylating Agents. Chem. Res. Toxicol., 26, 156−168 (2013).
Gold, B. Combating infectious disease. Drug resistance: the problem that keeps on giving. Future Med. Chem. 5, 981-982 (2013).
Szulik, M, Voehler, M., Ganguly, M., Gold, B. and Stone, M. P. Site-specific stabilization of DNA by a tethered major groove amine, 7-aminomethyl-7-deaza-2'-deoxyguanosine. Biochemistry 52, 7659-7668 (2013).
Monti, P., Foggetti, G., Menichini, P. Inga, A., Gold, B. and Fronza, G. Comparison of the biological effects of MMS and Me-lex, a minor groove methylating agent: clarifying the role of N3-methyladenine. Mutat. Res. 759, 45-51 (2014).
Gold, B., Stone, M. P. and Marky, L. A. Looking for Waldo: A potential thermodynamic signature to DNA damage. Acc. Chem. Res., 47, 1446-1454.
DNA Damage: Roles in Toxicity and Mutagenicity