Alicia D. Powers

Alicia D. Powers

Degree Program: Chemical and Biological Engineering
Faculty Advisor: Sean P. Palecek
Phone: (608) 265-3502
Email: adpowers@wisc.edu

 

 

 

 

 

Current Research

Overactive and overexpressed kinases have been implicated in the cause and progression of many types of cancers. Kinase inhibitors offer a targeted approach for treating cancers associated with increased or deregulated kinase activity. Sometimes, however, cancer cells exhibit initial resistance to these inhibitors or evolve to develop resistance during treatment. Additionally, cancers of any one tissue type are often heterogeneous in their mechanisms of oncogenesis, and thus diagnosis of a particular type of cancer does not provide insight into what kinase therapies may be effective. For example, while some lung cancers overexpressing EGFR kinase respond to treatment with EGFR kinase inhibitors, other lung cancers overexpress Met kinase and are thus resistant to treatment with EGFR kinase inhibitors. Here we describe a microfluidic-based assay for quantifying Met kinase activity in cancer cell lysates with the goal of predicting responsiveness to Met inhibitors and development of resistance to these inhibitors. In this assay, we immobilized a phosphorylation substrate for Met kinase onto a glass microscope slide. We then exposed the substrate to a cancer cell lysate and detected substrate phosphorylation using a fluorescently-conjugated antibody. This assay is able to quantitatively detect Met kinase activity in whole cell lysate from as few as 300 cancer cells as well as detect Met kinase in a background of up to 75% non-cancerous cells. Additionally, it can detect kinase inhibition by the general kinase inhibitor genistein as well as the specific kinase inhibitors SU11274 and PHA665752, giving it potential predictive capability for patient response to kinase inhibitors.

Publications

Powers AD, Liu B, Lee AG, Palecek SP. Macroporous hydrogel micropillars for quantifying Met kinase activity in cancer cell lysates. Analyst 2012, 137(17):4052-61.

Abstract (PDF)

Resume (PDF)

 

 

 


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