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 Description

 

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.

Selected Publications 

• Salerno P, De Falco V, Tamburrino A, Nappi TC, Vecchio G, Schweppe RE, Bollag G, Santoro M, Salvatore G. Cytostatic activity of adenosine triphosphate-competitive kinase inhibitors in BRAF mutant thyroid carcinoma cells. J Clin Endocrinol Metab. 2010 Jan;95(1):450-5. PUBMED

Schweppe RE, Kerege AA, Sharma V, Poczobutt JM, Gutierrez-Hartmann A, Grzywa RL, Haugen BR. Distinct genetic alterations in the mitogen-activated protein kinase pathway dictate sensitivity of thyroid cancer cells to mitogen-activated protein kinase kinase 1/2 inhibition. Thyroid. 2009 Aug;19(8):825-35. PUBMED

• Old WM, Shabb JB, Houel S, Wang H, Couts KL, Yen CY, Litman ES, Croy CH, Meyer-Arendt K, Miranda JG, Brown RA, Witze ES, Schweppe RE, Resing KA, Ahn NG. Functional proteomics identifies targets of phosphorylation by B-Raf signaling in melanoma. Mol Cell. 2009 Apr 10;34(1):115-31. PUBMED

Schweppe RE, Kerege AA, French JD, Sharma V, Grzywa RL, Haugen BR. Inhibition of Src with AZD0530 reveals the Src-Focal Adhesion kinase complex as a novel therapeutic target in papillary and anaplastic thyroid cancer. J Clin Endocrinol Metab. 2009 Jun;94(6):2199-203. PUBMED

Schweppe RE, Klopper JP, Korch C, Pugazhenthi U, Benezra M, Knauf JA, Fagin JA, Marlow LA, Copland JA, Smallridge RC, Haugen BR. Deoxyribonucleic acid profiling analysis of 40 human thyroid cancer cell lines reveals cross-contamination resulting in cell line redundancy and misidentification. J Clin Endocrinol Metab. 2008 Nov;93(11):4331-41. PUBMED

Schweppe RE, Cheung TH, Ahn NG. Global gene expression analysis of ERK5 and ERK1/2 signaling reveals a role for HIF-1 in ERK5-mediated responses. J Biol Chem. 2006 Jul 28;281(30):20993-1003. PUBMED

Education

Coming Soon!

Reasearch Interests

 

·        Thyroid Cancer

·        Oncogenic Signaling Mechanisms

·        Molecular Targeted Therapies