Current Research:

The Gold laboratory has three areas of interest.

-The use of molecules that sequence specifically bind to duplex DNA via triple helix formation is an attractive strategy to alter gene expression by blocking access of transcription factors to their major groove DNA binding domains, to probe transcriptional regulatory sequences, and to affect gene correction through targeted homologous recombination. We have synthesized a series of heterocyclic C-glycosides that form triplex structures with DNA. Efforts are underway to evaluate and exploit the biological activities of these molecules.
-It is not known why many carcinogens and anticancer drugs react with DNA in a sequence-selective manner that results in unique patterns of DNA damage, and eventually in unique distributions and types of mutations. We hypothesize that there is an electrostatic information recognition scheme embedded in DNA sequence that we refer to as the Sequence-Dependent Electrostatic Landscape (SDEL). To study this fundamental question, we are synthesizing modified nucleotides that will allow us to inhibit or impose cation localization at specific positions in the major groove of DNA .
-Many carcinogens and anticancer drugs covalently react with DNA to afford a diverse mixture of products. This a barrier to being able to attribute the biological role(s) of individual DNA lesions to the mutagenic and/or toxic potency of the agent. This issue is important in the design of new anticancer drugs that are cytotoxic without being mutagenic, i.e., will not induce secondary cancers. We are studying molecules that form DNA adducts that are cytotoxic but not mutagenic.

Bio:

Barry Gold is Professor and Chair of 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.