DAVID WAXMAN, Ph.D.
Professor of Cell & Molecular Biology and Medicine
Department of Biochemistry
Office: J5 Cummington street
Phone: (617) 353-7401
Electronic Mail:
djw@bu.edu
Research Interests:
Humans, like other mammals, are exposed to a large number of toxic foreign chemicals, many of which are lipophilic and have a tendency to persist in fatty tissues. In response to this environmental challenge, mammals have evolved a large number of genes which encode cytochromes P450 and other enzymes that oxygenate lipophilic foreign compounds. Expression of these genes is controlledby a complex array of molecular regulatory circuits that respond to varying physiological conditions and changes in hormonal and environmental stimuli. In addition to metabolizing foreign chemicals, P450 enzymes hydroxylate physiological substrates, such as steroid hormones, arachidonic acid and cholesterol, which both compete with drug and other foreign chemical substrates and can regulate P450 metabolism through the modulation of P450 gene expression.
A major goal of our laboratory is to elucidate these metabolic processes at both the biochemical level and the molecular regulatory level. One of our research projects involves the regulation of liver P450 gene expression by the temporal pattern of pituitary growth hormone (GH) release. Other ongoing studies concern the regulation of these enzymes and their genes by factors such as thyroid hormone, circadian rhythms and non-genotoxic carcinogens classified as peroxisome proliferators. A second important goal of our laboratory is to identify ways through which our understanding of P450 biochemistry and gene regulation may be applied to improve human health. These efforts are exemplified by our development of cytochrome P450 as a model for cancer gene therapy using drug-susceptibility genes. P450 genes have great promise for applications designed to enhance the sensitivity of tumor cells to cancer chemotherapeutic drugs.
