|Nitric Oxide: Chemistry and Pathophysiology
Our laboratory has been interested for many years in the formation, distribution, and metabolism of nitrate, nitrite, and N-nitroso compounds. This work led to our discovery of the endogenous synthesis of nitrogen oxides and eventually the discovery of nitric oxide as a biological molecule. At present our laboratory is conducting research on the pathophysiological consequences of nitric oxide and its oxidation products. This encompasses cell-mediated nitrosation, free-radical reactions, and oxidation. We are particularly interested in the nature of chemical damage to DNA and its genotoxic consequences. From a health point of view this is important for the inflammatory state and for various infections and diseases that increase the risk of cancer. We are also interested in the inhibition of these reactions by antioxidants and other substances that offer protection from oxidative stress.
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Tissue Engineering for Drug Development and Chemical Toxicity
Cells placed in culture generally lose at least some key differentiated physiological functions that they normally exhibit as part of organized tissues in the body. Thus, while cultured cells may be adequate for some applications in drug metabolism and detection of toxins, they are certain to fail for others. We have developed an in vitro organized tissue-based sensor for detection of unknown toxins and rapid screening of drug metabolism. The technology combines a unique chip-based micro tissue arrangement with mass spectrometric and optical sensors to detect changes in tissue behavior and measure primary and secondary biochemical transformations of drugs and toxins.
Quantitative Ultramicro Measurements for Drug
and Carcinogen Metabolism
We are developing new approaches to measure the fate of drugs and chemicals in the classical paradigm for drug metabolism: Absorption, Distribution, Metabolism, Excretion (ADME). The methods include variations in biological Mass Spectrometry and Laser-Induced Fluorescence Spectroscopy. An important new, unique tool is an Accelerator Mass Spectrometer for C14 and tritium that will be directly coupled to gas and liquid chromatography. These tools will enable us to conduct "Nanotracing" of molecules in humans at heretofore unexplored levels.