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overview
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Research in the Eblen lab focuses on the roles of serine-threonine protein kinases in cancer biology, particularly in ovarian and breast cancer. The research is primarily focused on the MAP kinase family, which regulate a number of cellular processes throughout the cell, including proliferation, migration, gene expression and drug resistance. These diverse roles are carried out by phosphorylation of dozens of target proteins throughout the cell. Changes in gene expression and kinase activation can greatly affect the biology of cancer cells. Areas of research interest include identification of novel MAP kinase substrates, regulation of MAP kinase activation by cellular adhesion and biological outcomes of signaling events.
The laboratory uses a bioengineered system to identify novel MAP kinase substrates through use of a mutant MAP kinase that has been designed to uniquely utilize analogs of ATP. This method allows for the specific labeling of direct substrates of MAP kinases in a complex mixture of proteins, followed by the identification of the substrates by mass spectrometry. The laboratory has identified novel targets of the MAP kinase ERK2, some of which may have specific implications for ovarian cancer. In addition, similar mutants of p38 are used in a mouse model system of breast cancer to determine substrates of p38 involved in breast cancer progression.
Another research interest in the lab is the regulation of MAP Kinase activation by cellular adhesion, which is important for anchorage independent growth and metastasis. We have uncovered some novel aspects of this regulation specific to ovarian cancer cell lines and are currently characterizing them. These mechanisms appear to be involved in the acquisition of anchorage-independent growth of ovarian cancer cells, which could have implications for cell survival and proliferation in peritoneal ascites fluid.
Multicellular spheroids in the ascites fluid of ovarian cancer patients represent a population of cells that increase intraperitoneal metastasis and exhibit greater resistance to chemotherapeutic agents. The laboratory has a focus in determining how protein kinase signaling in spheroids regulates acquired drug resistance. The goal of this work is to develop novel therapeutic interventions in kinase signaling pathways for the treatment of ovarian cancer.
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