B.Sc. University of British Columbia, 1991
Ph.D. University of British Columbia, 1998
NSERC Postdoctoral Fellow, University of Munich, 1998-1999

Plants produce a great diversity of natural products (phytochemicals), many of which are used as medicines or are important dietary constituents. The Page Lab is tapping the biosynthetic potential of the plant kingdom by studying the enzymes and metabolic pathways leading to bioactive natural products. We use a blend of genomics, biochemistry and metabolite analysis to discover genes encoding enzymes involved in natural product biosynthesis and the transcription factors that control pathways. Target pathways are those leading to terpenoids, terpenophenolics and alkaloids. We also conduct research aimed at identifying phytochemicals that prevent disease through their ability to induce phase 2 proteins in mammalian cells.

Projects underway in the lab include:

1. Terpenophenolic biosynthesis in hop and hemp

Terpenophenolics, also known as prenylated polyketides, are unusual natural products derived from isoprenoid and phenolic precursors. Despite being a relatively small group of plant metabolites, terpenophenolics have bioactivities that make them important for human health. Prominent examples of terpenophenolics with pharmacological properties are cannabinoids (e.g. D9-tetrahydocannabinol, THC) in Cannabis sativa L. (hemp, marijuana) and xanthohumol, a prenylflavonoid from in hop (Humulus lupulus). We are identifying genes encoding biosynthetic enzymes from hop and cannabis using a comparative genomics approach involving EST sequencing of trichome-specific cDNA libraries. Identification of key genes will allow for improved breeding and metabolic engineering of terpenophenolic pathways in these plants.

2. Functional genomics of alkaloid metabolism

Functional genomics methods using virus-induced gene silencing (VIGS) promise to both speed up gene discovery and allow for the cloning of novel genes inaccessible to traditional mutagenesis approaches. We use tobacco rattle virus (TRV) to silence genes in Nicotiana benthamiana, a member of the Solanaceae that produces nicotine and serves as a model for other alkaloid-producing plants. The targets of our VIGS experiments are enzymes involved in alkaloid biosynthesis, and transcription factors that regulate this pathway. This project aims to provide information useful in the biotechnological modification of pharmaceutical alkaloid production.

3. Identification of cytoprotective phytochemicals from food and medicinal plants

The consumption of a diet rich in phytochemicals has been linked to reduced incidence of many diseases, including cancer and cardiovascular disease. Many phytochemicals with health-promoting activities exert their effects through the induction of an "indirect" antioxidant response mediated through phase 2 proteins. Prominent examples of such compounds are sulforaphane from broccoli and xanthohumol from hops. We have an ongoing program to test extracts of herbal medicines and food plants to determine if they induce phase 2 proteins in cultured mammalian cells. Bioassay-guided fractionation is employed as a means to isolate and identify the active constituents of extract "hits". Through this project we hope to both provide information in support of the consumption of dietary phytochemicals and to identify nutraceuticals for the supplement industry.