Steven R. Tannenbaum, Ph.D., is a Professor of Chemistry and Toxicology and the Director of the Division of Bioengineering and Environmental Health. Dr. Tannenbaum studies the etiology of cancer in high-risk populations. This is done by developing appropriate in vivo and in vitro models for comparison and extrapolation to humans, and through the measurement of carcinogen adducts covalently bound to biological macromolecules. Dr. Tannenbaum is developing analytical methods for the quantitation of toxicologically significant compounds by monitoring their reaction products in human or animal blood. The proposed method would be applicable to many carcinogens, mutagens, and other reactive chemicals. The results would allow more accurate assessments of human risk, and more precise epidemiological investigations of the links, for example, between exposure to carcinogens and human cancer. N-nitroso compounds may be formed endogenously from nitrite and a variety of nitrogen-containing compounds. The substances thus formed may be toxic and carcinogenic and have been implicated in the etiology of certain cancers in humans, including that of the stomach, lower GI tract, bladder, and esophagus. Dr. Tannenbaum's research program encompasses many of the factors which influence this process.
Gerald N. Wogan, MS, Ph.D. is Underwood-Prescott Professor of Bioengineering and Environmental Health, Professor of Chemistry. He studies the molecular and cellular effects of carcinogen exposure. Many chemically inert compounds can be metabolically converted in the tissues of animals and humans to reactive derivatives. Covalent binding of these derivatives to cellular macromolecules, especially DNA, is associated with various toxic manifestations including cancer, mutation, or cell death. Elucidation of these molecular interactions is crucial to an understanding of the mechanisms underlying toxic responses. Several experimental models are being applied with this objective. Other studies focus on binding of chemical carcinogens to macromolecules, in particular DNA, which can elicit a variety of cellular responses, some of which lead to malignancy. Carcinogen-induced alterations in DNA can lead to changes in expression of transforming genes. In many types of human tumors, altered expression of cellular proto-oncogenes is associated with mutations in specific regions of the genes, which lead to changes in the primary sequence of the encoded gene product. Animal and tissue culture models have been developed to define the sequence of events that follows the exposure of cells to chemical carcinogens, and the temporal relationship between the formation of DNA-carcinogen adducts and the activation of proto-oncogenes to the development of a pre-neoplastic cell phenotype and the subsequent development of tumors.
Peter C. Dedon, MD, Ph.D., is an Associate Professor of Bioengineering and Environmental Health. His work includes the interactions of most genotoxins with DNA, which have been studied with isolated, naked DNA, an essential simplification for determining gross chemical mechanisms. DNA rarely exists as such in the living organism, however, in which it is packaged along with proteins into the compact mass of chromatin. There is evidence to suggest that chromatin structure changes the way genotoxins interact with DNA in vivo, and it is the long-term objective of the research in Dr. Dedon's laboratory to delineate the rules that govern the interactions of small molecules with chromatin from toxicologic, pharmacologic and biochemical points of view. An understanding of the role that chromatin structures play in the biochemistry of DNA-interactive agents is essential to the design of selective chemotherapeutic agents and chemical probes of DNA and chromatin structure, and to the understanding of the mechanisms of mutagenicity, carcinogenicity, and DNA-directed toxicity of small molecules.
Timothy C. Wang, MD, Professor of Medicine at the Columbia University, has an active NIH supported collaboration of Helicobacter associated gastric cancer with Dr. Fox. Timothy Wang is also Chief of the Division of Digestive and Liver Disease at Columbia and has extensive experience in in vivo molecular techniques constructing transgenics and knockouts. His current research is dissecting the pathophysiology of gastrin on target tissue using these genetically manipulated mice.
Bruce Horwitz, MD, PhD - Assistant Professor at the Harvard Medical School is one of the Division's research collaborators. He has extensive experience developing immuno-deficient animal models and in performig complex adoptive transfer and radiation chimera experiments.