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Dr. Schweppe received her Ph.D. in Biochemistry from the University of Colorado Health Sciences Center and carried out her post-doctoral studies with Dr. Natalie Ahn where she used proteomic and genomic strategies to study molecular responses to MAP kinase signaling pathways as they relate to cancer progression. Dr. Schweppe joined the Division of Endocrinology as an Assistant Professor in 2006. Dr. Schweppe’s research is directed toward identifying novel molecular targets relevant to papillary and anaplastic thyroid cancer (PTC and ATC), with the ultimate goal of advancing these studies into clinical trials for thyroid cancer patients who do not respond to standard therapies.

Project #1
The mitogen activated protein kinase (MAPK) pathway plays an important role in PTC and ATC. Dr. Schweppe and others have shown that the growth and invasion of PTC and ATC cells are differentially sensitive to MAPK pathway inhibitors (Schweppe et al 2009 Thyroid). Her current interests are to identify signaling mechanisms associated with deregulated MAP kinase signaling and sensitivity and resistance to MAPK pathway inhibitors.

Project #2
Src and Focal Adhesion Kinase (FAK) are both overexpressed and/or activated in many types of cancer. Recently, Src inhibitors, including AZD0530 (Saracatinib) and BMS-354825 (Dasatinib) have entered human clinical trials. FAK and Src signaling and the efficacy of Src inhibitors has not been studied in thyroid cancer. We were the first to report that FAK and Src are phosphorylated in the majority of thyroid cancer cell lines (Schweppe et al 2009 J Clin Endocrinol Metab). We have further shown that treatment of PTC and ATC cells with Saracatinib selectively inhibits the growth and invasion of cells expressing elevated levels of phospho-FAK. Finally, we show that phospho-FAK is present in a subset of PTC tumor samples. These studies provide the first evidence that FAK is activated in PTC and ATC, and that the FAK-Src complex represents a viable therapeutic target for a subset of patients with advanced thyroid cancer. The goals of our current studies are to characterize the mechanisms by which certain cell lines are sensitive to Src inhibition to help direct therapy and identify new therapeutic targets.

Project #3
Drs. Haugen and Schweppe recently received an NIH Challenge Grant (15-CA-103) along with Drs. James Fagin and Jeffrey Knauf at Memorial Sloan Kettering to generate a panel of comprehensively characterized thyroid cancer cell lines. Our goals are to apply global molecular and genomic approaches with novel computational analyses to the new and existing thyroid cancer cell lines to uncover pathways important in thyroid cancer development and progression.