Ductal carcinoma in situ (DCIS) is a precursor to invasive breast cancer, and the protein psoriasin is one of the most highly expressed genes in DCIS. Psoriasin is present at abnormally high levels in many pre-invasive breast cancer cells and in a smaller subgroup of invasive breast cancer cells. Recent research has shown that the interaction of psoriasin with the signaling protein Jab1 may be a keystone of the signal network of the breast cancer cell, and that psoriasin binding can cause Jab1 to stimulate the development of invasive and metastatic breast cancer cells. Inhibiting protein-protein interactions is an exciting new approach in the search for targeted cancer therapeutics, and the psoriasin-Jab1 interaction is a promising new target for the treatment of breast cancer. Dr. Fraser Hof’s work deals with fundamental questions about the interactions of proteins and small molecules and with the applied design of small molecule therapeutics. His proposal is to design and develop novel drug molecules to block this psoriasin-Jab1 interaction, first to validate the target and then to guide subsequent drug development. A drug that inhibits this interaction may offer a novel therapy to directly target pre-invasive breast cancer and prevent the development of invasive breast cancer. This therapy may also hold promise as a new approach to target the small subgroup of invasive breast cancers where psoriasin is also present, as this subgroup is typically not eligible for current targeted therapies such as tamoxifen and herceptin.