Investigators and Program Directors

Research Interests

The overall objective of this laboratory is to apply molecular genetics tools to the study of human toxicology. The focus is on the in vivo function and mechanisms of regulation of microsomal cytochrome P450 monooxygenases, which metabolize numerous drugs, chemical carcinogens, environmental pollutants, as well as endogenous signaling molecules such as steroid hormones and eicosanoids. One major area of current research involves development of conventional and conditional knockout mouse models to determine the roles of extrahepatic P450 enzymes in target tissue metabolic activation and tissue-selective toxicity of environmental agents. These mouse models will also be used to explore the potential biological functions of extrahepatic biotransformation enzymes in various organ systems, such as the brain and the olfactory chemosensory organ. Complementary to these studies in animal models, there are continuous efforts to characterize the P450s and other biotransformation enzymes expressed in human tissues, with an emphasis on the respiratory tract and the application of a genomics approach, and to identify the genetic polymorphisms of selected human P450 genes. A particularly interesting P450 gene is CYP2A13, which is expressed selectively in the respiratory tract, and is highly active in the metabolic activation of known tobacco-related carcinogens. A long-term goal is to identify the genetic variations that predispose human subpopulations to chemical toxicity. In addition, there are on-going studies on the mechanisms of tissue-specific and xenobiotic-induced P450 gene expression. Current focus in this area is on the identification and characterization of novel transcription factors responsible for the tissue-specific transcriptional activation of the CYP2A genes. These studies will further our understanding of the mechanisms of toxicity of environmental chemicals, and may provide better methods for determining the risk associated with environmental exposure and possible preventive measures for environmental diseases.

Contact Information

Phone: (518) 486-2585
Fax: (518) 486-1505
E-mail: xding@wadsworth.org