The sequencing of the human genome marked the beginning of a collective scientific expedition to understand complex organisms. Genes, of course, merely contain the instructions for which proteins will populate the cell. Untangling the multi-faceted networks that regulate complex organisms and their diseases will require innovative technologies to globally monitor many classes of biomolecules, including nucleic acids, proteins, and metabolites. High-throughput technologies for gene and transcript measurement are well-developed and broadly accessible, and, as such, have had a fantastic and transformative impact on modern biology and medicine. For numerous reasons, methods for global analysis of proteins and metabolites - crucial biological effector molecules - are less evolved and markedly less accessible. The overarching mission of my program is to (1) facilitate expedient, comprehensive analysis of proteins and metabolites by innovating new mass spectrometric technologies and (2) apply these techniques to advance biomedical research. To accomplish these goals we center our efforts on four main areas: Instrumentation and Informatics, Proteomic Methodology, Metabolomics, and Biomedical Applications. First, leveraging our extensive electron transfer dissociation (ETD) development history, we plan to expand our ability to interrogate many currently intractable peptides, post-translational modification (PTMs), and other biomolecules. Second, with these and other tools, we will simplify and expedite proteome analysis; we envision analyzing an entire proteome (>10,000 proteins) or PTMome (>10,000 phosphorylation sites) in hours, or even minutes. Third, by development of novel chemical instrumentation and software tools, we will advance the field of metabolite profiling and discovery. Finally, the above mentioned technologies are most meaningfully developed in the context of relevant biology and, therefore, we plan to apply our innovative tools to many cutting-edge biomedical projects.
The overarching mission of this project is to facilitate expedient, comprehensive analysis of proteins and metabolites by development of new chemical measurement technologies. These tools will then be applied to the study of numerous human diseases including Alzheimer's spectrum disorder, mitochondrial dysfunction, cancer, diabetes.
| Hebert, Alexander S; Thöing, Christian; Riley, Nicholas M et al. (2018) Improved Precursor Characterization for Data-Dependent Mass Spectrometry. Anal Chem 90:2333-2340 |
| Reidenbach, Andrew G; Kemmerer, Zachary A; Aydin, Deniz et al. (2018) Conserved Lipid and Small-Molecule Modulation of COQ8 Reveals Regulation of the Ancient Kinase-like UbiB Family. Cell Chem Biol 25:154-165.e11 |
| Jha, Pooja; McDevitt, Molly T; Gupta, Rahul et al. (2018) Systems Analyses Reveal Physiological Roles and Genetic Regulators of Liver Lipid Species. Cell Syst 6:722-733.e6 |
| Hebert, Alexander S; Prasad, Satendra; Belford, Michael W et al. (2018) Comprehensive Single-Shot Proteomics with FAIMS on a Hybrid Orbitrap Mass Spectrometer. Anal Chem 90:9529-9537 |
| Mitok, Kelly A; Freiberger, Elyse C; Schueler, Kathryn L et al. (2018) Islet proteomics reveals genetic variation in dopamine production resulting in altered insulin secretion. J Biol Chem 293:5860-5877 |
| Rhoads, Timothy W; Burhans, Maggie S; Chen, Vincent B et al. (2018) Caloric Restriction Engages Hepatic RNA Processing Mechanisms in Rhesus Monkeys. Cell Metab 27:677-688.e5 |
| Riley, Nicholas M; Westphall, Michael S; Coon, Joshua J (2018) Sequencing Larger Intact Proteins (30-70 kDa) with Activated Ion Electron Transfer Dissociation. J Am Soc Mass Spectrom 29:140-149 |
| Lapointe, Christopher P; Stefely, Jonathan A; Jochem, Adam et al. (2018) Multi-omics Reveal Specific Targets of the RNA-Binding Protein Puf3p and Its Orchestration of Mitochondrial Biogenesis. Cell Syst 6:125-135.e6 |
| Bucci, Michael D; Weisenhorn, Erin; Haws, Spencer et al. (2018) An Autophagy-Independent Role for ATG41 in Sulfur Metabolism During Zinc Deficiency. Genetics 208:1115-1130 |
| Riley, Nicholas M; Coon, Joshua J (2018) The Role of Electron Transfer Dissociation in Modern Proteomics. Anal Chem 90:40-64 |
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