My lab is conducting two distinct research projects. In the first project, we are investigating the mechanisms that control the uptake and homeostasis of iron. This project has important implications both for our basic understanding of these mechanisms, and also for our ability to manipulate the iron content of particular plant parts as a means of improving the iron nutritional quality of food. In the second project, we are using molecular approaches to discover genes involved in production of paclitaxel (generic name for Taxol™ - Bristol-Myers Squibb). Genes discovered during this project will improve our ability to supply sufficient quantities of paclitaxel to the world. Iron is one of the most important and most problematic of all the micronutrients used by living organisms. Iron is an essential cofactor for many cellular redox reactions, yet the same high reactivity that makes it so useful can cause cellular damage if iron is not carefully controlled. Add to this problem that iron is also only sparingly soluble in aqueous solution, and it is easy to see why plants have evolved multifaceted iron homeostatic mechanisms. These mechanisms include control of uptake, translocation from organ to organ and cell to cell, re-mobilization of stored iron, as well as poorly understood sensing and signaling systems by which the plant communicates its iron status between tissues. Many of the mechanisms involved in plant iron homeostasis are not well understood, and this is a major obstacle to devising approaches for biofortification of staple foods with iron. Biofortification refers to the genetic engineering of staple crops to accumulate additional bioavailable iron in edible parts; it is widely regarded as a sustainable means of improving the iron nutrition of the 2-3 billion people worldwide whose inadequate diet causes iron deficiency anemia. My group has a strong interest in the processes by which plants move iron and other transition metals within their above ground parts. We have recently shown that members of the Yellow Stripe Like (YSL) family of transporters are required for normal iron, zinc, and copper loading into both vegetative and reproductive tissues. In future, my group will continue to perform experiments that will elucidate the mechanisms that plants use to achieve correct distribution of iron and other metals into above ground organs and seeds. We will also pursue experiments that will elucidate the function(s) of additional YSL family members both at the biochemical and whole plant physiological levels. We are using molecular approaches to delineate global metabolic control of taxol (paclitaxel) in Taxus cell cultures. Paclitaxel is a valuable pharmaceutical currently used primarily for treatment of cancer, but which has also been found to reduce major adverse cardiac events when coated onto coronary stents, and which is being tested in the treatment of Alzheimer’s disease and other neurodegenerative disorders characterized by altered microtubule networks. Because two to four mature trees are needed to supply enough paclitaxel for the treatment of one patient, supply of paclitaxel from natural sources was limiting, and alternative methods of production such as cell culture systems for production are actively sought. The biosynthesis of paclitaxel is complex, and molecular analysis of the system has been limited to work on the biosynthetic genes themselves. We are using transcription profiling to identify genes involved in global metabolic control. Such genes will be involved not just in paclitaxel biosynthesis (where all current efforts are focused), but also in transcriptional regulation, transport, secretion and degradation. Most recently, we have identified a transcription factor from yew (Taxus cuspidata) that is capable of activating transcription from the promoters of several of the genes for paclitaxel biosynthesis. Our identification of a protein that may regulate the biosynthesis of this compound is an important step forward in efforts to engineer cultured yew cells for enhanced production of paclitaxel.

Plant Development and Molecular Genetics, Iron Homeostasis in Plants, Paclitaxel biosynthesis