Catherine Fenselau

Catherine Fenselau Research

Historically our research program has focused on the exploitation of mass spectrometry in biomedical research. Through the last fifteen years we have helped to open proteomics, the post-genomic science that provides global interrogation of proteins in high throughput workflows. We have contributed novel methods for sample preparation, which facilitate high throughput mass spectrometry-based proteomic workflows and quantitative comparisons of protein abundances. Applications of our novel workflows are underway to answer questions about the resistance of tumors to both chemotherapy and immunotherapy.

Interrogation of the plasma membrane. Our approach to studies of cellular proteomes is built on the isolation of sub-cellular organelles. This preliminary fractionation provides functional context and successful interrogation of higher numbers of proteins. The most difficult organelle to isolate is the plasma membrane. However, proteins in the plasma membrane control cell signaling and metabolite transport, and they make up the majority of current drug targets. We are optimizing the use of nanoparticle pellicles to facilitate isolation of the plasma membrane from other cellular components (Rahbar and Fenselau. J. Prot. Res. 2004, 3: 1267) and we are recently funded for collaborative studies of the plasma membrane in myeloid-derived suppressor cells.

Proteomic strategies based on longer peptides. Classic proteomic workflows analyze tryptic peptides, which generally weigh less than 3000 Da. Compelling reasons to work with longer peptides include enhanced capability to recognize coordinated protein modifications. We have introduced microwave-accelerated acid cleavage, which produces longer peptides with selective cleavage at aspartic acid residues (Swatkoski et al, J. Prot. Res. 7: 579, 2008.). We are optimizing a "middle-down" workflow to analyze these oligopeptides, exploiting the capability of the LTQ-Orbitrap to provide high resolution measurements on both precursor and product ions in MS/MS experiments (Cannon et al, J. Prot. Res. 2010, 9: 3886).

Rapid characterization of microorganisms. This laboratory first introduced the use of mass spectrometry to analyze whole bacteria by detecting intact biomarkers characteristic of different genus and species. Currently we are developing proteomic and bioinformatic strategies that allow rapid identification of bacteria, spores, protein toxins and viruses, with particular emphasis on characterization of genetically engineered bacteria, bacteria without sequenced genomes (Wynne et al, Proteomics 2010, 10: 3631), and bacteria in mixtures.