This proposal requests funds for a Fourier transform Orbitrap Fusion Lumos Tribrid mass spectrometer with ETD capability to empower a highly accomplished group of investigators at Johns Hopkins University School of Medicine, Johns Hopkins Whiting School of Engineering and the Johns Hopkins Bloomberg School of Public Health in their clinical and basic science related explorations. Today, even though this type of mass spectrometer is virtually indispensable both for discovery studies in which proteins and peptides that might be responsible for a given disease are to be identified and for detailed characterization of protein and peptides as to allow an understanding of the fundamental biological processes, clinicians and researchers at Johns Hopkins are not currently equipped with such an instrument. Ready availability of this instrument will permit protein characterization and analysis of select types of post-translational modifications for which this mass spectrometer has no parallel. The user group of the proposed mass spectrometer includes several investigators who are leaders of large NIH Roadmap or Program Project type initiatives and employ mass spectrometry as a critical component of their research. These initiatives include the Clinical Proteomics Tumor Analysis Consortium (U24 CA160036), Udall Center of Excellence for Parkinson's Disease Research (P50 NS038377), Johns Hopkins Technology Center for Networks and Pathways of Lysine Modification (U54 RR020839), Specialized Center to Investigate Plasticity at the Excitatory Synapse (P50 MH100024), The Johns Hopkins Proteomics Innovation Center in Heart Failure (HHSN268201000032C), SPORE in Breast Cancer (P50 CA088843), SPORE in GI Cancer (P50 CA62924) and a Program of Excellence in Glycosciences (P01 HL107153). Access to this instrument will enhance our understanding of a number of disease areas and has the potential to generate key therapeutic targets and biomarkers, which define the era of personalized medicine. Monitoring of these proteins or post-translational modifications will allow prediction of disease risk such as that for diabetes and heart disease, permit early detection of diseases such as Parkinson's disease and pancreatic cancer, enable monitoring of therapeutic responses to drugs, provide an opportunity to customize therapeutics in cancers such as breast cancer and help early identification of cases with a disease relapse by simple tests such as a blood test. In short, this instrument will help th scientists and physicians at Johns Hopkins help define the future of medicine and biomedical research.
This proposal requests funds for an advanced Fourier transform Orbitrap Fusion Lumos Tribrid ETD mass spectrometer capable of identifying low abundance proteins, peptides, proteoforms and post-translational modifications (e.g. phosphorylation, O-GlcNAc, ubiquitylation) with very high sensitivity, resolution, and fast scan speeds from large numbers of biological or clinical samples. By accurately measuring molecular alterations in various clinical and model systems, it is our hope that the requested experimental platform will facilitate a systems biology approach to studying human diseases, permit monitoring the outcomes of clinical therapies and help identify novel biomarkers, pathogenic pathways and/or drug targets. This instrument will be employed by a group of highly accomplished biomedical investigators at Johns Hopkins in studies pertaining to breast cancer, pancreatic cancer, diabetes and Parkinson's disease in addition to other investigations that will elucidate basic biology related to critical cellular processes, gene expression and transcriptional regulation.
