Research Abstract:
Alterations of signal transduction pathways play a significant role in the growth and metastasis of human cancers. We focus on the Her2/neu receptor tyrosine kinase, a member of the EGFR growth factor receptor family, which is gene amplified and activated in about 25% of human breast cancer cases. Several drugs that target Her2/neu are used in the treatment of Her2-positive breast cancer, such as a monoclonal antibody to the extracellular portion of the receptor or small molecule kinase inhibitors, but resistance to these drugs has frequently been seen in patients. Better understanding of Her2/neu and the downstream signal transduction pathways it uses will provide improved treatment for breast cancer patients.
Our lab studies signal transduction pathways in breast cancer using a variety of approaches involving biochemistry, proteomics, and cell biology. Fundamental questions that we are interested in are:
-- What are the mechanisms that activate and regulate Her2/neu?
-- What is the network of signal proteins that is activated by protein kinases in breast cancer and how can we study them using systems biology approaches?
-- What are the molecular alterations that give rise to breast cancer and how can our knowledge of signal transduction and proteomics be used to improve cancer treatment for patients?
Proteomics is the large-scale identification and characterization of proteins and it can be used to provide deeper insights into these pathways by identifying novel proteins and sites of post-translational modifications. We have previously published a large proteomic study of Her2/neu signaling in cell lines and are currently working on performing proteomic experiments in animal models.
Research in the Bose lab is divided into the following project areas:
Project Area 1: Proteomics Studies of Her2/neu Signal Transduction
Project Area 2: In vitro Biochemistry and Structural Biology experiments to define the mechanisms of activation and regulation of the Her2/neu and Her4 kinases.
Project Area 3: Genome Sequencing of Breast Cancer
Please come talk to us to get more details about this research. We are very interested in having graduate students come to the lab for rotations.
Selected Publications:
Bose R and Zhang X. The ErbB Kinase Domain: Structural Perspectives into Kinase Activation and Inhibition. Experimental Cell Research 2009 315:649-58.
Zhang X, Pickin KA, Bose R, Jura N, Cole PA, and Kuriyan J. Inhibition of the EGF Receptor by Binding of MIG6 to an Activating Kinase Domain Interface. Nature 2007 450:741-744.
Bose R, Molina H, Patterson AS, Bitok JK, Periaswamy B, Bader JS, Pandey A and Cole PA. Phosphoproteomic Analysis of Her2/neu Signaling and Inhibition. Proc Natl Acad Sci USA 2006 103:9773-9778.
Last Updated: 08/20/2009 |