Research Abstract
The main area of our research involves the use of high resolution mass spectrometry to quantitatively study protein complexes, post-translational modifications, metabolomics and lipidomics in signaling pathways for diseases such as cancer. The goal is to identify new targets for drugs that specifically inhibit the defective pathways that are driving cell growth, proliferation and metastasis. We recently developed a mass spectrometry approach for label-free quantitative proteomics based on the average and total signal values of the peptide LC/MS/MS spectra identified from each protein. Using this approach, we can determine the stoichiometry of proteins in a complex as well as determining whether a particular member of the protein complex is up- or down-regulated upon stimulation, drug treatment or between disease states. Two approaches can be used to quantitatively study signaling pathways: a targeted approach that focuses on particular proteins or their post-translational modifications or an unbiased discovery approach where we look for members of a protein complex in a pathway to regulate growth and proliferation. We use these techniques for quantifying proteins and post-translational modifications between different cellular conditions and have published several of these studies with collaborators and users of my mass spectrometry core.
In the past five years, we have developed the instrumentation and expertise for quantitative global metabolite profiling of complex biological samples. This includes both steady state measurements of nearly 300 metabolites and timed flux analyses of 13C/15N-labeled metabolites. We have shown that we can profile polar metabolites from tumor tissue, fixed tissue, cells and bodily fluids using this technology. Most recently, we have developed an untargeted lipidomics profiling platform capable of identifying more than 1500 lipid species. Our latest studies involve the integration of proteomics, metabolomics and lipidomics in platforms that we name either tri-omics or serial-omics if we start from a single specimen such as a tumor biopsy, dried blood spot, etc.
In addition to research activities, as the director of one of the medical center's core facilities, I provide service to local researchers in their quest to cure and treat debilitating diseases such as cancer. The services go beyond instrumental analyses but extend to help in grant writing and presentations to local laboratories and investigators. I am committed to this endeavor of providing service to the academic and clinical research community.