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Chemical Engineering Research Seminar
Cain Department of Chemical Engineering
Louisiana State University
Cancer is a highly heterogeneous disease with significant differences between patients (intertumor heterogeneity) and among cells in the tumor microenvironment (intratumor heterogeneity) requiring a multi-faceted approach to obtain a greater fundamental understanding of the driving forces behind metastasis and developed drug resistance. The focus of my research group is developing new bioanalytical techniques to study drug resistance in multiple myeloma and creating better preclinical models to study metastasis in breast cancer. Multiple myeloma is a cancer of plasma cells that has found to be treatable by inhibiting enzymes associated with protein degradation including the proteasome and deubiquitinating enzymes (DUBs): however, there is a substantial variation in the patient response with some patients exhibiting an inherent (or developed) resistance to the drugs due to substantial heterogeneity within the cancer. To elucidate this, we have developed long-lived, cell-permeable, enzyme specific, fluorescent biosensors to directly measure DUB and proteasome activity in intact myeloma cells. Our findings demonstrate substantial heterogeneity among cells including the identification of subpopulations of cells with enhanced enzyme activity which could be resistant to DUB- and proteasome-based therapeutics.
The next part of the talk with focus on the development of a suite of microfluidic devices to study various aspects of the breast cancer metastatic cascade. Approximately 90% of breast cancer-related deaths are due to the presence of secondary (or metastatic) tumors that occur throughout the body. These secondary tumors have been shown to be more aggressive and drug resistant when compared to the primary tumor; however, the underlying mechanisms driving this resistance are still unclear due to the lack of available preclinical models. Using a suite of three different microfluidic devices we show how cancer cells manipulate healthy cells and their environment to drive drug resistance and how biophysical forces cells experience during metastasis alters cellular phenotype.
Adam Melvin obtained a BS in Chemical Engineering and a BA in Chemistry from the University of Arizona, a MS in Chemical Engineering (with a minor in Biotechnology) and a PhD in Chemical Engineering from North Carolina State University. He was an NIH postdoctoral fellow at the University of North Carolina at Chapel Hill in the Departments of Chemistry and Biomedical Engineering. In August of 2013, he joined the faculty in the Cain Department of Chemical Engineering at Louisiana State University. His research interests focus on biochemical/biomedical engineering including the design of peptide-based biosensors and therapeutics and the development of novel microfluidic platforms to model the breast cancer tumor microenvironment and perform high-throughput single cell analysis. He is an NSF CAREER awardee and has received numerous teaching and mentoring awards during his time at LSU.
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