on making them attractive in the prevention of a multifactorial disease process like atherosclerosis. Two Ayurvedic herbals, gugulipid and curcuminoids, appear to have hypolipidemic, antioxidant and anti- inflammatory effects in humans. In this protocol, Dr. Szapary will primarily study the hypolipidemic effects of standardized extracts of curcuminoids and gugulipid in two RCTs. These trials will assess the safety and efficacy of these two agents when used alone and in combination, as done in Ayurvedic medicine, over a 3 to 6 month period. In addition, Dr. Szapary will examine their effects on state of the art biomarkers of oxidant stress and vascular micro-inflammation, both of which are important processes in the pathogenesis of atherosclerosis. These studies will help define the role of these herbal therapies in the prevention of atherosclerosis, and serve as a model for the critical evaluation of dietary supplements in cardiovascular disease.

Increased expression of the Fibroblast growth factor 8 (Fgf8) gene plays an important role in the progression of both breast and prostate cancer. To understand how abnormal Fgf8 expression affects cell function, we are studying its normal role during vertebrate embryogenesis, using the mouse as a model system. Fgf8 is expressed in a variety of regions of the embryo that may be termed "organizers": regions that are a source of signals that pattern and thus "organize" the surrounding tissue. An allelic series generated at the Fgf8 locus (Meyers et al. 1998 Nature Genetics 18:136), as well as Cre-mediated tissue-specific knockouts (Lewandoski et al. 2000 Nature Genetics, 26:460; Lewandoski 2001 Nature Reviews Genet. 2:743) has revealed a role for Fgf8 in organizers that control gastrulation, limb, and brain development. Recently we have produced a valuable mouse line (TCre) that expresses Cre throughout all embryonic mesodermal lineages but not ectoderm/neuroedctoderm, thus allowing us to control gene expression in these lineages. This line is useful to bypass the embryoni