The Kelleher Group has three primary lines of research focused on Top Down Proteomics, Natural Products Discovery and Biosynthesis and Chromatin Oncobiology and DNA-Damage.  An underlying focus, driving all lines of research, is our continued push towards optimizing instrumentation and bioinformatic approaches to best suit the unique needs of a Top Down analysis. 

The main focus for our Top Down Proteomics subgroup is to push the limits for whole proteome analysis of mammalian cells, striving for a future in which Top Down analysis rivals that of Bottom Up in the number of protein identifications per run.  Recently we have seen progress towards this very goal with the introduction of a separation platform specifically designed to minimize the most common problem in Top Down Proteomics, intact protein separations.  This platform effectively reduces sample complexity and separates proteins depending on size, resulting in an opportunity for the researcher to select the optimal analysis method for the sample.

Our Natural Products subgroup is focused on the discovery and biosynthesis of novel natural products.  Developments from this subgroup include the introduction of the PrISM platform, geared towards the identification of natural products synthesized by nonribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs) without prior knowledge of a gene sequence.  This is made possible by our ability to detect a phosphopantetheinyl (Ppant) ejection marker ion for NRPS/PKS thiolation domains.  We also work in collaboration with groups from other universities to provide mass spectrometry analysis of novel biochemical systems.

We also have a long-standing interest in histone analysis.  Our Chromatin Oncobiology and DNA-Damage subgroup continues to dig deeper into the "histone code", a complex mixture of post-translational modifications that together determine a host of cellular processes.  We are interested in visualizing dynamic histone PTM changes simultaneously on multiple sites.  Through application of technology developed in our Top Down Proteomics subgroup, we are able to apply "Precision Proteomics" to histone analysis.