Barbara L. Weber, MD Medline search Professor of Medicine Genetics Director, Cancer Genomics Program Director, Breast Cancer Program, Abramson Family Cancer Research Institute 514 BRBII/III 421 Curie Blvd. Philadelphia, PA 19104-6160 215-898-0247 phone 215-573-2486 fax Research: Our laboratory is focused on understanding the molecular events that lead to the development of breast cancer. We have used the study of inherited forms of breast cancer as a means of identifying and characterizing genes that are important in this process. We are interested in both high penetrance genes and the more common low penetrance, or modifier, genes. As an extension of this work we are now using microarray-based transcriptional profiling and array-based comparative genomic hybridization to characterize genetic changes that occur as normal breast epithelium undergoes malignant transformation through a series of premalignant lesions. Out current efforts at defining the function of the BRCA1 protein are focused on the development of genetic models. We are developing a human cell line model as well as a mouse model and have preliminary data to suggest a yeast model may also be useful. We will also use a microarray-based system to examine differences in gene regulation in model cells with and without functional BRCA1 protein. This allow the identification of both known and novel genes which are up or down-regulated by BRCA1 and place them in the context of entire cellular pathways.