The Yale Keck MS and Proteomics Resource has developed and integrated a high throughput metabolomics workflow that utilizes the robustness of a high flow Ultra-Pressure Liquid Chromatography (UPLC) system in an emerging mass spectrometry based model. This model is for validating and quantifying metabolites and small molecules which provide a prospective classification and confirmation of bio-molecular markers from large clinical cohorts. As evident by the current instrument usage (based on the number of samples injected), our metabolomics workflow was immediately recognized by researchers at Yale and other institutions as an important biotechnological tool to efficiently and cost effectivey process their large study cohorts. Due to our development of these protocols utilizing a demo UPLC system, we are requesting funding to purchase a permanent ACQUITY UPLC H-Class system to be coupled to our existing 4000 QTRAP mass spectrometer which is the platform the metabolomics workflow was developed on. If funded, the permanent UPLC system would provide continued access with 83% instrument usage by the 7 Major NIH-funded users who supported this application, along with 11 Minor users utilizing the remaining >17% of the requested UPLC system. These investigators from Yale, 4 nearby (Harvard, Columbia University Medical Center, U.Conn Medical Center, and New York Medical College) and 2 other US (U. of Colorado at Denver and U. of Mississippi Medical Center) Institutions propose to use our Targeted metabolomics service to advance diverse biomedical research on: Diabetes, Obesity, Pulmonary Sarcoidosis, Corneal Antiangiogensis, Alcohol metabolism, Tissue injury, Melanoma, Neuronal Ceroid Lipofuscinosis, Autism, Lyme disease, Insulin resistance in Pregnancy, and Aging. The requested UPLC system will also enable our developed metabolomics workflow to be made available to the 218 investigators from 81 institutions and companies who used the services provided by the Yale Keck MS and Proteomics Resource in 2013. Progress in this metabolomics workflow will advance knowledge of how best to understand, prevent, prognose, and treat human diseases. The requested UPLC system and the associated metabolomics workflow would be unique at Yale University, and would be available to other interested investigators due to its placement in a core resource facility that accepts samples from across the U.S. and (when needed to keep its instrumentation operating at capacity) from around the world. Thus, the UPLC system would significantly contribute to biomedical research at Yale University and beyond.
The requested UPLC system is urgently required to address the rapid growth in targeted metabolomics technologies needed to bear on a very broad range of NIH-funded basic, translational, and clinical biomedical projects that support this application. This proposed research would bring advanced tools to discover novel targets and treat behavioral alteration in obesity, determine the molecular mechanism of progressive lung fibrosis and chronic obstructive pulmonary disease, accelerate advent of novel therapy for Sarcoidosis, test druggable targets for corneal antifibrosis, study photochemistry of melanin for use in preventing skin cancer and slowing neurodegenerative disease, elucidate alteration in sphingosine and palmitate metabolism to mechanistically study Neuronal Ceroid Lipofuscinosis, discover therapeutic agents in bacterial symbionts, determine predictive circulating markers in healthy and predisposition to accelerated functional decline in aging and diabetes, study metabolic signaling pathways along the gut-brain axis to obtain critical insights into the pathogenesis of Autism spectrum disorders, interrogate pathogenesis of Lyme disease, and to determine novel treatment strategies for insulin and metabolites effect on weight gain during pregnancy
| Carlyle, Becky C; Kitchen, Robert R; Kanyo, Jean E et al. (2017) A multiregional proteomic survey of the postnatal human brain. Nat Neurosci 20:1787-1795 |
