Research in the Koomen Laboratory focuses on analytical chemistry development, elucidation of biological processes, and implementation of clinical assays using proteomics and quantitative mass spectrometry. Much of this work is performed using multiple reaction monitoring (MRM); three examples are detailed below.
In colon cancer, broad scale proteomics employing relative quantification techniques and gene expression profiles have determined candidate biomarkers related to the Adenomatous Polyposis Coli protein. Targeted analysis of this panel of proteins coupled with the interrogation of protein expression in relevant signaling pathways, including Wnt, TGF/SMAD, and Notch, in tumors and adjacent normal tissue can be used to select and evaluate candidate biomarkers for predicting patient outcomes.
In multiple myeloma, the same techniques and technologies are being applied in cell lines to develop preclinical models that will provide a molecular basis for rational chemotherapy. In these experiments, direct drug targets and apoptosis-related proteins are being monitored in parallel with specific signaling pathways, including NFkB. These data will elucidate mechanisms of drug resistance and provide another method to evaluate combination therapy.
Finally, direct patient assessment is being performed in multiple myeloma using MRM. Current clinical assays use gel or capillary electrophoresis to measure the antibody secreted by the myeloma, which is used to stage the patients and estimate tumor burden. Quantitative mass spectrometry should be significantly more sensitive at detecting and quantifying these antibodies. Improvements in the analytical technique would lead to earlier detection of disease relapse, more rapid intervention with second line therapies, and potentially improved patient outcomes. These projects share the common goal of changing the standard of patient assessment and care using mass spectrometry.