Professor Ian Phillips

Research

Research Interests:

My research is concerned with understanding the molecular mechanisms by which organisms protect themselves against the effects of potentially harmful foreign chemicals.

It is concentrated on two families of enzymes, the flavin-containing monooxygenases (FMOs) and the cytochromes P450 (CYPs), that are of central importance in the metabolism of a wide range of foreign hydrophobic compounds, including many therapeutic drugs, chemical carcinogens and environmental pollutants.

Regulation of gene expression

We are investigating the molecular mechanisms that regulate the differential developmental and tissue-specific expression of FMO genes. Other work is aimed at elucidating the molecular mechanisms and signalling pathways by which barbiturates selectively induce the CYP required for their detoxification.

Inherited disorders

We have established that loss-of-function mutations of FMO3 cause the inherited disorder trimethylaminuria, or fish-odour syndrome. Affected individuals are unable to metabolize dietary-derived trimethylamine and consequently excrete the smelly free amine, which imparts an odour characteristic of rotting fish. We are investigating the molecular pathology of the disorder and developing potential therapies.

Physiological roles of FMOs

Knockout mice bearing targeted disruptions of specific FMO genes are being used to investigate the roles of FMOs in development and homeostasis and in the multipathway metabolism of therapeutic drugs and toxic chemicals.

Pharmacogenetics

We are investigating the effect of genetic polymorphisms of human FMOs on the ability of individuals to metabolize drugs and toxic chemicals and the consequences of this for human health and disease. Also of interest is how this genetic variation has been shaped by natural selection and population history.

Publications

• Browse a list of publications by Ian Phillips