Professor, Department of Pharmacology and Chemical Biology, Director, Women's Cancer Research Center, University of Pittsburgh Cancer Institute
The goal of the Lee laboratory is translational breast cancer research. The laboratory has two main areas of focus.
The first involves targeting the insulin-like growth factor pathway in breast cancer. A major emphasis is upon the downstream signaling intermediates the insulin receptor substrates (IRSs) analyzing interactions with steroid hormone receptors (ER and PR), role in normal mouse mammary gland development, mechanisms of transformation of mammary epithelial cells in vitro and in mouse models, and roles in human breast cancer. These studies include a systems biology approach to understanding the pathway that includes use of transcriptomics (RNA-seq) and proteomics (Reverse Phase Protein Arrays).
The second area of research is the role of next generation sequencing in personalized cancer genomic medicine. This work includes basic studies on mutations in breast cancer and then methods (both technical and computational) to apply this in the clinical setting. Studies examine tumor heterogeneity and molecular changes during progression, with a particular focus on DNA and RNA structural rearrangements. Analysis includes use of long-insert mate-pair, whole genome, whole exome and RNA-sequencing which have all been completed on a set of 20 biopsies to allow an unprecedented integrated view of genomic and transcriptomic changes during progression. Genomic alterations are measured in blood using targeted sequencing and ddPCR. Computational methods are being developed and optimized for analyzing clonal architecture, evolutionary genomic change, and refinement of structural rearrangements. The laboratory is also developing a breast cancer specific next-generation sequencing test for clinical sequencing and developing a computational architecture for integration of patient genomic and phenotypic data for research and clinical (Oracle Translational Research Center) use.