CYTOCHROME P4501A1

大多数药物和其他外源性药物在…之前被广泛代谢

Most drugs and other xenobiotics are extensively metabolized prior to elimination. Although this can be a beneficial process, e.g. activation of a pro-drug to its pharmacologically active derivative, metabolism can also lead to pathological effects. Although several enzyme systems are known to participate in this activity, the cytochromes P450 and flavin-containing monooxygenases (FMO) are widely recognized as the major players in at least the initial steps of this process. The AI has established an active research program to elucidate factors controlling the expression of the human CYP1A1 gene and the predominant FMO. Current work is focused on the interaction of a repressor with the CYP1A1 gene which appears to modulate its inducibility. Tissue-specific control mechanisms are being explored for FMO1 and 2 in the rabbit and BMO3 in the human. Possible polymorphisms in the human FMO3 gene are also being explored. The AI currently has five full-time and one rotating Ph.D. students in his laboratory. Students are recruited both from the Pharmacology and Cancer Biology graduate programs. The decision to work in one laboratory or another are largely based on the rotation experience. Quite often, the students dissertation project is an extension of work performed during the rotation. Students have ample opportunities to attend departmental seminars and to participate in a journal Club. In the latter, an emphasis is placed on a critical evaluation of recent publications of interest. The laboratory holds regular meting wherein laboratory personnel are encouraged to discuss current results and problems they might be encountering in specific experimental approaches. Students are given the opportunity to help in the review of papers the AI receives for evaluation in his role on various editorial boards. Students are also encouraged to subunit their work to national meetings and if accepted, funds are provided for them to attend. Finally, the AI has established a process to aid the students in remaining focused on their specific projects which usually results in a good publication record and a timely finish to their graduate training.