Peroxisome Proliferator-Activated Receptors (PPARs)
Research in my laboratory is focused on the cell-specific roles of the peroxisome proliferator-activated receptors (PPARs), of which there are three family members (alpha, delta/beta and gamma), with respect to cancer. PPARs are ligand-activated transcription factors, belonging to the nuclear receptor superfamily, that regulate expression of downstream target genes containing specific promoter recognition sequences known as peroxisome proliferator responsive elements (PPREs). PPARs are themselves expressed in a number of cell/tissue types. For example, PPARg expression has been identified in adipocytes (fat cells), and cells of the breast, liver, colon, prostate, and cardiovascular and immune systems. Several synthetic compounds used to successfully treat various human disorders for many years, and now identified as PPAR ligands, helped establish critical regulatory roles for PPARs in lipid and glucose metabolism. Interestingly, in vitro and in vivo studies since the late 1990s have suggested the PPARs may play important roles in carcinogenesis. However, the molecular mechanisms linking PPARs to the regulation of cell growth and transformation are only partially understood.
Currently, our goal is to gain a thorough understanding of the processes involved in breast cancer at the genetic, cellular and whole body levels. The laboratory is using state-of-the-art methods to complement in vivo PPAR knockout mouse studies with in vitro and molecular techniques. Ultimately, we aim to develop innovative strategies for identifying those individuals at increased risk for breast cancer, improve the effectiveness of the therapeutic approaches used, and hopefully prevent this disease in susceptible populations.